Ancient Greek and Roman gynecologists believed that women were naturally more prone to  humoral imbalance  and therefore illness. For example, women were more likely to become "moist". It was believed that the female body had more water than the male body. Ancient doctors thought that puberty, specifically the menarche, could be caused through an excess of fluid buildup in the female body, and thus menstruation was the body's way of regulating its fluid and humoral balance. [ 36 ]  This idea led to Roman doctors not taking notice of problematic menstrual cycles; excessive and minimal menstruation were medical problems noticed by doctors. [ 37 ]   Pliny the Elder , a Roman naturalist, [ 38 ]  wrote that menstrual fluid could wither fruit, cause insanity in dogs, dull mirrors, rust iron and bronze, kill bees, pollute purple fabrics, cause miscarriages in horses and humans, and sour crops. [ 39 ]  He also believed that if a woman menstruated during a solar or lunar eclipse, sexual intercourse could result in death. Pliny stated that the touch of a menstruating woman could treat medical conditions such as  gout , fevers,  erysipelas ,  scrofula ,  skin cancer , and  bites from rabid dogs . [ 40 ]  Aside from medicinal uses, Pliny listed a number of supernatural uses. For example, magi could not perform any magic feats if their doorsteps had been touched by menstrual blood. It was also believed that menstrual fluid could contaminate entrances, and therefore households. [ 41 ] [ 39 ]


Ancient Roman doctors such as  Aetius  believed that  amenorrhea , [ 42 ]  or the absence of a  menstrual cycle , was caused by a "hot temperament". Soranus noticed  psychosomatic  causes of this condition; in this scenario he advised no treatment. He also believed that this condition could be caused by a lack of a feminine body, he recommended restricting food intake to reshape the body.  Cucumbers ,  grapes , and  wine  were also used to treat this condition. [ 43 ]  It could also be treated with an incision into the  hymen . This therapy was also used to treat  dysmenorrhea , which the Romans called "retention of the menstrual flux". It is a menstrual disorder characterized by pelvic, abdominal, or back pain resulting from menstruation. [ 44 ] [ 45 ]   Chamomile  is a type of daisy-like plant that ancient Roman woman used to treat dysmenorrhea. [ 46 ]  Venipuncture through leeches was another kind of treatment for this disorder. [ 47 ]  In ancient Rome, women with heavy menstrual bleeding would be treated by applying ligatures to the groin and to the armpits, thus blocking off blood flow throughout the body. It was theorized this also resulted in the reduction of blood flow to the uterus. Following this, blunt corks, liquid pitch, and pessaries soaked with  alum , plant sap, or the yolk of roasted eggs were inserted inside the vagina. [ 48 ] [ 49 ]   Premenstrual syndrome , a condition leading to severe abnormalities prior to menstruation, [ 50 ]  may have been noticed by Roman doctors. Roman doctors stated that menstruation occurs all at once in a specific moment each month, it is possible this theory was designed to account for the syndrome. [ 51 ]


Vaginal bleeding  is the expulsion of blood from the vagina. [ 52 ]  Galen described a woman suffering from this condition, or what he described as the "female flux". Other names for this condition included the "abnormal flux", "menstrual flux", and "hemorrhage of the uterus". [ 37 ]   Juvenal  was a Roman poet notable for his  Satires . [ 53 ]  In these works, he occasionally described what we know to be vaginal discharge, which is the collection of cells, bacteria, and liquid used to protect and lubricate the vagina. [ 54 ] [ 55 ]  He wrote about a "great torrent of sheer lust" running down a woman's legs at the idea of engaging in "energetic" interactions with a man. Juvenal also stated that "No woman will say no to her moist vulva", and he describes an adulteress coming home with a fluid on her dress, possibly semen or vaginal discharge. [ 56 ]


Hegar dilators  are  dilators  used to treat  vaginismus  and induce  cervical  dilation, and for  inflatable penile implant  procedures, though for penile implants it has been shown that outcomes are better  without  dilation. [ 1 ] [ 2 ]
 [ 3 ] [ 4 ]


Hegar dilators were developed and introduced by  Alfred Hegar  in 1879 originally for use in the field of  gynecology . [ 5 ]  Typically, dilators are a set of metal rods of increasing diameters, from a few millimeters up to 26 millimeters. The rods are round, slightly curved, and have a conal tip. Some sets have conal tips at both ends, while others have one end flattened for easy handling. [ 6 ]  Hegar dilators are typically marked with a Hegar number that is equivalent to its size in millimeters (e.g., a Hegar size 8 is 8 mm thick). Commercially available Hegar dilators are commonly sold in sets of 8, 10, or 14 individual rods. [ 7 ]  Each set includes a range of sizes, popularly from 3 mm to 17 mm for single-ended dilators or 3 mm / 4 mm to 17 mm / 18 mm for double-ended dilators, though configurations with sizes anywhere from 1 mm to 26 mm do exist. [ 8 ] [ 9 ]


Hegar dilators are used to treat  vaginismus , also known as genito-pelvic pain disorder. [ 4 ] [ 3 ]  Patients with vaginismus use Hegar dilators of gradually increasing size, potentially followed by penetration by their partner. [ 10 ]  They have also found application in the management of  hymenal  stenosis. [ 11 ] [ 12 ]


Hegar dilators are used to induce  cervical dilation  in order to gain entry to the interior of the  uterus .


During the process of dilation, the  cervix  may have to be stabilized with a  tenaculum , and then the dilators are slowly entered into the cervical canal with a lubricant, starting with a thin, low Hegar number rod and progressing gradually to larger numbers. [ 13 ]  The dilators can also be used to sound the uterus.


Laminaria  rods have also been used to open up the cervix but work slowly as they increase size by absorbing water.


Typical non-gynecological uses include dilating a stenotic percutaneous gastrostomy stoma, anal dilation and urethral dilation in the case of stricture or stenosis.


Hegar dilators (commonly, sizes 11 and 12) have been used during the insertion of two intracorporal cylinders into the  corpus cavernosum penis  during  penile implant  procedures, but it has been shown that outcomes are better  without  this dilation, which destroys erectile tissue. [ 1 ] [ 2 ]  These cylinders are inflated and deflated by a pump that moves sterile saline under pressure between a holding reservoir and the cylinders, inflating or deflating an erection of the penis. [ 14 ]


High-grade serous carcinoma  ( HGSC ) is a type of tumour that arises from the  serous  epithelial layer in the  abdominopelvic cavity  and is mainly found in the  ovary . HGSCs make up the majority of  ovarian cancer  cases [ 1 ]  and have the lowest survival rates. [ 2 ]
HGSC is distinct from  low-grade serous carcinoma  (LGSC) which arises from ovarian tissue, is less aggressive and is present in stage I ovarian cancer where tumours are localised to the ovary.


Although originally thought to arise from the  squamous  epithelial cell layer covering the ovary, HGSC is now thought to originate in the Fallopian tube epithelium. HGSC is much more invasive than LGSC with a higher fatality rate - although it is more sensitive to  platinum-based chemotherapy , [ 3 ] [ 4 ]  possibly due to its rapid growth rate. In rare cases, HGSCs can develop from LGSCs, [ 5 ]  but generally the two types arise independently of each other.


The ‘incessant  ovulation ’ theory is suggested by the strong  correlation  between the number of ovulatory cycles of an individual and their risk of ovarian cancer. [ 6 ]


This trend is reflected in the protective effects of pregnancy, parity and breastfeeding against ovarian cancer, [ 7 ] [ 8 ]  and similar findings in epidemiological studies that have indicated a reduction of risk associated with use of oral contraceptive pills. [ 9 ] [ 6 ]


Ovulation is accepted as the cause of ovarian cortical inclusion cysts, the precursor  lesions  of serous carcinomas, and lower numbers of these cortical inclusion cysts are thought to be the mechanism by which reducing lifetime ovulations can lower the risk of developing HGSC. [ 10 ]


Conversely, a temporal association with  menopausal hormone therapy  and incidence of HGSC was found, [ 11 ]  and  polycystic ovarian syndrome  (PCOS) was shown to contribute to a doubling of the risk of ovarian cancer. [ 12 ]


Endometriosis  can increase risk for other ovarian cancer subtypes, but is not associated with HGSC. [ 13 ]


More than 20% of ovarian cancer tumours have  hereditary  origin. The majority of these feature mutations in the tumour suppressor  BRCA  genes, which tend to give rise to HGSC. [ 14 ]  A mutation in  BRCA1  or  BRCA2  can confer a lifetime ovarian cancer risk of 40-50% and 10-20% respectively, [ 15 ]  with BRCA2 mutations strongly associated with better clinical outcomes.


A specific tumour protein 53 ( TP53 )  expression pattern in the Fallopian tube epithelium – the ‘p53 signature’ - is thought to be a precursor marker of HGSC. TP53-/- mice (in which the TP53 gene has been deleted) do not develop ovarian carcinomas. [ 16 ]  However, TP53 mutations were found in 96% of HGSC cases. [ 17 ]  A local abnormal TP53 expression may thus be indicative of HGSC. [ 18 ]  In women, pelvic HGSC show either a complete absence of P53 expression, or overexpression, suggesting that any aberration of P53 leads to tumour development. [ 19 ]  Additionally, overexpression of TP53 is associated with better clinical outcome whereas an absence of the p53 protein is linked to an increased risk of HGSC tumour recurrence. [ 19 ]


A recent mouse model suggest that a p53 mutation may induce HGSC arising from the ovary rather than the Fallopian tube. [ 20 ]


HGSC are further distinguished from LGSC by ‘type I/II’ ovarian tumour nomenclature; [ 21 ]  type I referring to tumour types (e.g. LGSCs) where precursor lesions within the ovary have been characterised, and type II referring to tumour types (e.g. HGSCs) without association of such lesions, tumours understood to develop  de novo  from the tubal and/or ovarian surface epithelium. This classification has more relevance to research rather than to clinical practice. [ 22 ]


The  serous  membrane is a particular type of secretory epithelium which covers organs in body cavities and secretes serous fluid to reduce friction from muscle movement. Serous membrane lining the abdominopelvic cavity is called the  peritoneum ; that lining heart and mediastinum is the  pericardium , and that lining the thoracic cavity and lungs is the  pleura . Technically a ‘serous carcinoma’ can occur anywhere on these membranes, but high-grade serous carcinoma is generally limited to the peritoneal area.


While until recently HGSC was thought to arise from simple differentiation of cortical inclusion cysts (CICs) of  ovarian surface epithelium  (OSE), the cell origin of HGSC is now understood to be much more complex, with evidence for other sites of origin, both intra- and extra-ovarian, having come to light.


Opposing:


'Coelomic hypothesis'  [ 24 ]


Supporting:


The common Müllerian origin of the Fallopian tubes, uterus, cervix, and upper vagina has resulted in the proposal that peritoneal high-grade serous carcinoma is a spectrum of a single disease. [ 22 ]


Relevant animal models of HGSC can only be developed when the cell origin is properly understood. However, as HGSC tends to have the same clinical behaviour, regardless of its primary cell origin, determining cell origin is less important for clinical treatment, but may be of relevance when looking for biomarkers.


The specific process by which a HGSC arises may be related to the BRCA mutation status of the individual, [ 32 ] [ 36 ]  as well as the p53 mutation status. [ 20 ]


A 2007 paper describes the process of determining cell of origin as “Tumour origin is typically assigned to the organ presenting with the dominant tumour mass. The one exception is the peritoneum, which is classified as a primary site only if a candidate origin is not found in the endometrium, tube or ovary”. [ 37 ]


It is recognised that HGSC can have variable and complex primary origins, but understanding and determining this will give insight into its pathogenesis.


Assuming a fimbrial origin, as observed in the majority of HGSC cases, [ 28 ]  the current understanding of HGSC genesis suggests a process by which STIC fimbrial cells implant into the ovary as cortical inclusion cysts through the ovulation rupture site.


To account for instances where there is no STIC involvement, endosalpingiosis or  de novo  metaplasia of ovarian surface epithelium inclusions are also possible. A much rarer occurrence is the differentiation of HGSC from LGSC. [ 5 ]


Symptoms include persistent  bloating , postmenopausal bleeding, and/or appetite loss. [ 38 ]


Transvaginal ultrasonography  as well as cancer marker  CA125  level analysis is often used to determine potential malignancy of suspect pelvic masses. [ 39 ]


Surgical  staging  is the procedure by which the abdominal cavity and lymph nodes are examined for malignant tissue, usually via  laparoscopy . Tissue  biopsies  may be taken for further analysis. It is not until this histological analysis stage that actual diagnosis of HGSC can be made. [ 39 ]


If glands are seen to fuse with intricate, extensive papillae featuring epithelial tufting with solid nests surrounded by a space alongside irregular slit-like spaces, then serous carcinoma is suspected.


Distinguishing between LGSC and HGSC: [ 40 ]


Distinction of HGSC from high-grade endometrioid carcinoma is not always possible. [ 40 ]


The progression of HGSC may also be determined from examining the  cadherin  expression profile. [ 41 ]


As ovarian cancer is rarely symptomatic until an advanced stage, [ 42 ]  regular pre-emptive screening is a particularly important tool for avoiding the late stage at which most patients present. However, A 2011 US study found that transvaginal ultrasound and cancer marker CA125 screening did not reduce ovarian cancer mortality. [ 43 ]  In contrast, a more recent UK study found that up to 20% of ovarian cancer deaths could be prevented through annual performance of these procedures. [ 44 ]


Prevention for an individual deemed at risk of HGSC has, up until recently, been (bilateral or unilateral) removal of both the ovary and the Fallopian tube (salpingo- oophorectomy ).


With hormonal and even morbidity issues resulting from ovary removal, and the increased evidence for the role of the Fallopian tubes HGSC pathogenesis, optimisation of this procedure has been to remove just the Fallopian tube(s) (salpingectomy) with the ovaries remaining until age of menopause  [ 45 ] [ 46 ]  - although critics of this argue that a reduced blood supply to the ovaries may induce premature menopause regardless. [ 47 ]


Prophylactic salpingo-oophorectomy is frequently performed in carriers of BRCA1 or BRCA2 mutations, [ 48 ]  although the benefits conferred by this procedure may vary dependent on the specific mutation. [ 49 ]


Tubal ligation is a less invasive prophylactic treatment shown to significantly reduce the risk of HGSC. [ 50 ]


Cytoreductive " debulking " surgery may be performed prior to chemotherapy treatment in order to decrease the physical mass of the tumour and thus reduce the number of chemotherapy cycles needed. [ 39 ]  The typical advanced presentation as well as extra-ovarian spread seen in HGSC can require aggressive debulking procedures. [ 51 ]  In some cases total abdominal  hysterectomy  will be performed, in other cases where the patient intends to bear children a salpingo-oophorectomy is performed instead.


Typical chemotherapy is six cycles of intraperitoneally-delivered platinum-base adjuvant chemotherapy with agents such as  carboplatin . [ 39 ]  Measurements of blood CA125 levels are used to determine patient response to the treatment.


Between 20% and 30% of patients relapse within six months of treatment. [ 52 ]


Poly ADP ribose polymerase  (PARP) inhibitors are another possible treatment, with carriers of BRCA1/2 mutations being the most responsive  [ 53 ] [ 54 ]


A study of incidence rates in the US between 1992 and 1999 found that the age-specific incidence rate for HGSC doubles every 10 years up until age 55, where it plateaus at approximately 20 cases per 100,000 women - before dropping dramatically after age 75. [ 55 ]


Ovarian cancer incidence rates are low in East Asia [ 56 ]  and highest in Europe, the United States, and Australia/New Zealand. [ 57 ]


Since 1975, survival rates for ovarian cancer have steadily improved with a mean decrease of 51% by 2006 of risk of death from ovarian cancer for an advanced stage tumour. [ 58 ]  The increase has mainly been due to successful extended life expectancy of affected patients rather than an improvement in cure rates.


A racial disparity exists between black and white women in the US, where black women experience a higher mortality risk from ovarian cancer. [ 58 ] [ 59 ]


The dimensions and shape of human  vaginas  are of great importance in  medicine  and  surgery , in addition to their relevance to  sexual pleasure  and  childbirth ; there appears to be no one way, however, to characterize the vagina's size and shape. [ 1 ]  In addition to variations from individual to individual, the size and shape of a vagina in the baseline state can vary substantially during  sexual arousal  and  intercourse . [ 2 ]


Carrying a baby to term,  i.e.  parity , is associated with a significant increase in the length of the  vaginal fornix . [ 1 ]  The potential effect of parity may be the result of a stretching and elongation of the birth canal at the time of  vaginal birth . [ 1 ]


There are a number of studies that have been done into the dimensions of the human vagina, but it has not been as intensively researched as  human penis size . [ 1 ]


A 1996 study by Pendergrass et al. using  vinyl polysiloxane  castings taken from the vaginas of 39  Caucasian  women, found the following ranges of dimensions: [ 3 ]


A second study by the same group showed significant variations in size and shape between the vaginas of women of different ethnic groups. [ 4 ]  Both studies showed a wide range of vaginal shapes, described by the researchers as "Parallel sided, conical, heart,   [...] slug" [ 3 ]  and "pumpkin seed" [ 4 ]  shapes. Barnhart et al., however, were not able to find any correlation amongst the race and the size of vagina. They were also unable to characterize the vaginal shape as a "heart, slug, pumpkin seed or parallel sides" as suggested by the previous studies. [ 1 ] [ 5 ]  A 2003 study by the group of Pendergrass et al. also using castings as a measurement method, measured vaginal surface areas ranging from 66 to 107 cm 2  (10.2 to 16.6 sq in) with a mean of 87 cm 2  (13.5 sq in) and a standard deviation of 7.8 cm 2  (1.21 sq in) [ 6 ]


Research published in 2006 by Barnhart et al., gave the following mean dimensions, based on  MRI scans  of 28 women: [ 1 ]


A 2006 U.S. study of vagina sizes using  Magnetic Resonance Imaging  (MRI) on 28 volunteers between 18 and 39 years old, with heights ranging from 1.5 to 1.7 metres (4 ft 11 in to 5 ft 7 in), and weights between 49.9 and 95.3 kilograms (110 and 210 lb), revealed a greater than 100 percent variation between the shortest (40.8 millimetres (1.61 in)) and the longest (95.0 millimetres (3.74 in)) vagina length. [ 7 ]


Given the large range in vaginal dimensions noted in studies such as the above, many fitted vaginal devices, for example  pessaries , do not adhere to a "one-size-fits-all" principle. [ 8 ]


Lawrence, citing  Masters and Johnson 's  Human Sexual Response  (1966), states that pages 73 and 74 of that book show that typical vaginal depth in Masters and Johnson's participants ranged from 7–8 cm (2.8–3.1 in) in an unstimulated state, to 11–12 cm (4.3–4.7 in) during  sexual arousal  with a  speculum  in place. [ 2 ]


Hysterectomy  is the surgical removal of the  uterus  and  cervix . Supracervical hysterectomy refers to removal of the uterus while the cervix is spared. These procedures may also involve removal of the  ovaries  ( oophorectomy ),  fallopian tubes  ( salpingectomy ), and other surrounding structures. The term “partial” or “total” hysterectomy are lay-terms that incorrectly describe the addition or omission of oophorectomy at the time of hysterectomy. These procedures are usually performed by a  gynecologist . Removal of the uterus renders the patient unable to bear children (as does removal of  ovaries  and  fallopian tubes ) and has surgical risks as well as long-term effects, so the surgery is normally recommended only when other treatment options are not available or have failed. It is the second most commonly performed  gynecological surgical procedure , after  cesarean section , in the United States. [ 1 ]  Nearly 68 percent were performed for conditions such as  endometriosis ,  irregular bleeding , and  uterine fibroids . [ 1 ]  It is expected that the frequency of hysterectomies for non-malignant indications will continue to fall given the development of alternative treatment options. [ 2 ]


Hysterectomy is a major surgical procedure that has risks and benefits.  It affects the hormonal balance and overall health of patients. Because of this, hysterectomy is normally recommended as a last resort after pharmaceutical or other surgical options have been exhausted to remedy certain intractable and severe uterine/reproductive system conditions. There may be other reasons for a hysterectomy to be requested. Such conditions and/or indications include, but are not limited to: [ 3 ]


In 1995, the short-term mortality (within 40 days of surgery) was reported at 0.38 cases per 1000 when performed for benign causes. Risks for surgical complications were presence of fibroids, younger age (vascular pelvis with higher bleeding risk and larger uterus), dysfunctional uterine bleeding and parity. [ 12 ]


The mortality rate is several times higher when performed in patients who are pregnant, have cancer or other complications. [ 13 ]


Long-term effect on all case mortality is relatively small. Women under the age of 45 years have a significantly increased long-term mortality that is believed to be caused by the hormonal side effects of hysterectomy and prophylactic oophorectomy. [ 14 ] [ 15 ]  This effect is not limited to pre-menopausal women; even women who have already entered menopause were shown to have experienced a decrease in long-term survivability post-oophorectomy. [ 16 ]


Approximately 35% of women after hysterectomy undergo another related surgery within 2 years. [ 17 ]


Ureteral injury is not uncommon and occurs in 0.2 per 1,000 cases of vaginal hysterectomy and 1.3 per 1,000 cases of abdominal hysterectomy. [ 18 ]  The injury usually occurs in the distal ureter close to the  infundibulopelvic ligament  or as a ureter crosses below the uterine artery, often from blind clamping and ligature placement to control hemorrhage. [ 19 ]


Hospital stay is 3 to 5 days or more for the abdominal procedure and between 1 and 2 days (but possibly longer) for vaginal or laparoscopically assisted vaginal procedures. [ 20 ]  After the procedure, the American College of Obstetricians and Gynecologists recommends not inserting anything into the vagina for the first 6 weeks (including inserting tampons or having sex). [ 21 ]


Removal of one or both ovaries is performed in a substantial number of hysterectomies that were intended to be ovary sparing. [ 22 ]


The average onset age of  menopause  after hysterectomy with ovarian conservation is 3.7 years earlier than average. [ 23 ]  This has been suggested to be due to the disruption of blood supply to the ovaries after a hysterectomy or due to missing endocrine feedback of the uterus. The function of the remaining ovaries is significantly affected in about 40% of people, some of them even require  hormone replacement therapy . Surprisingly, a similar and only slightly weaker effect has been observed for  endometrial ablation  which is often considered as an alternative to hysterectomy. [ 24 ]


A substantial number of women develop benign ovarian cysts after a hysterectomy. [ 25 ]


After hysterectomy for benign indications the majority of patients report improvement in sexual life and pelvic pain. A smaller share of patients report worsening of sexual life and other problems. The picture is significantly different for hysterectomy performed for malignant reasons; the procedure is often more radical with substantial side effects. [ 26 ] [ 27 ]  A proportion of patients who undergo a hysterectomy for chronic pelvic pain continue to have pelvic pain after a hysterectomy and develop  dyspareunia  (painful sexual intercourse). [ 28 ]


Estrogen levels fall sharply when the ovaries are removed, removing the protective effects of estrogen on the cardiovascular and skeletal systems. This condition is often referred to as "surgical menopause", although it is substantially different from a naturally occurring menopausal state; the former is a sudden hormonal shock to the body that causes rapid onset of menopausal symptoms such as hot flashes, while the latter is a gradually occurring decrease of hormonal levels over a period of years with uterus intact and ovaries able to produce hormones even after the cessation of menstrual periods. [ 29 ]


One study showed that risk of subsequent cardiovascular disease is substantially increased for women who had hysterectomy at age 50 or younger. No association was found for women undergoing the procedure after age 50. The risk is higher when ovaries are removed but still noticeable even when ovaries are preserved. [ 30 ]


Several other studies have found that  osteoporosis  (decrease in bone density) and increased risk of  bone fractures  are associated with hysterectomies. [ 31 ] [ 32 ]  This has been attributed to the modulatory effect of estrogen on calcium metabolism and the drop in serum estrogen levels after menopause can cause excessive loss of calcium leading to bone wasting.


Hysterectomies have also been linked with higher rates of heart disease and weakened bones. Those who have undergone a hysterectomy with both ovaries removed typically have reduced  testosterone  levels as compared to those left intact. [ 22 ]  Reduced levels of testosterone in women are predictive of height loss, which may occur as a result of reduced bone density, [ 33 ]  while increased  testosterone  levels in women are associated with a greater sense of sexual desire. [ 34 ]


Oophorectomy before the age of 45 is associated with a fivefold mortality from neurologic and mental disorders. [ 35 ]


Urinary incontinence and  vaginal prolapse  are well known adverse effects that develop with high frequency a very long time after the surgery. Typically, those complications develop 10–20 years after the surgery. [ 36 ]  For this reason exact numbers are not known, and risk factors are poorly understood. It is also unknown if the choice of surgical technique has any effect. It has been assessed that the risk for urinary incontinence is approximately doubled within 20 years after hysterectomy. One long-term study found a 2.4 fold increased risk for surgery to correct urinary stress incontinence following hysterectomy. [ 37 ] [ 38 ]


The risk for vaginal prolapse depends on factors such as number of vaginal deliveries, the difficulty of those deliveries, and the type of labor. [ 39 ]  Overall incidence is approximately doubled after hysterectomy. [ 40 ]


The formation of postoperative  adhesions  is a particular risk after hysterectomy because of the extent of dissection involved as well as the fact the hysterectomy wound is in the most gravity-dependent part of the pelvis into which a loop of bowel may easily fall. [ 41 ]  In one review,  incidence  of  small bowel obstruction  due to intestinal adhesion was found to be 15.6% in non-laparoscopic total abdominal hysterectomies vs. 0.0% in laparoscopic hysterectomies. [ 42 ]


Wound infection  occurs in approximately 3% of cases of abdominal hysterectomy. The risk is increased by obesity, diabetes, immunodeficiency disorder, use of systemic corticosteroids, smoking, wound hematoma, and preexisting infection such as chorioamnionitis and  pelvic inflammatory disease . [ 43 ]  Such wound infections mainly take the form of either  incisional abscess  or wound  cellulitis . Typically, both confer  erythema , but only an incisional abscess confers purulent drainage. The recommended treatment of an incisional abscess after hysterectomy is by  incision and drainage , and then coverage by a thin layer of  gauze  followed by sterile  dressing . The dressing should be changed and the wound irrigated with normal saline at least twice each day. In addition, it is recommended to administer an antibiotic active against staphylococci and streptococci, preferably  vancomycin  when there is a risk of  MRSA . [ 43 ]  The wound can be allowed to close by  secondary intention . Alternatively, if the infection is cleared and healthy granulation tissue is evident at the base of the wound, the edges of the incision may be reapproximated, such as by using  butterfly stitches ,  staples  or  sutures . [ 43 ]  Sexual intercourse remains possible after hysterectomy. Reconstructive surgery remains an option for women who have experienced benign and malignant conditions. [ 44 ]   : 1020–1348


Hysterectomy may cause an increased risk of the relatively rare  renal cell carcinoma . The increased risk is particularly pronounced for young women; the risk was lower after vaginally performed hysterectomies. [ 45 ]  Hormonal effects or injury of the ureter were considered as possible explanations. [ 46 ] [ 47 ]  In some cases the renal cell carcinoma may be a manifestation of an undiagnosed  hereditary leiomyomatosis and renal cell cancer  syndrome.


Removal of the uterus without removing the ovaries can produce a situation that on rare occasions can result in  ectopic pregnancy  due to an undetected fertilization that had yet to descend into the uterus before surgery. Two cases have been identified and profiled in an issue of the  Blackwell Journal of Obstetrics and Gynecology ; over 20 other cases have been discussed in additional medical literature. [ 48 ]  On very rare occasions, sexual intercourse after hysterectomy may cause a transvaginal evisceration of the small bowel. [ 49 ]  The  vaginal cuff  is the uppermost region of the vagina that has been sutured closed. A rare complication, it can dehisce and allow the evisceration of the small bowel into the vagina. [ 50 ]


Depending on the indication there are alternatives to hysterectomy:


Levonorgestrel intrauterine devices  are highly effective at controlling  dysfunctional uterine bleeding  (DUB) or  menorrhagia  and should be considered before any surgery. [ 51 ]


Menorrhagia (heavy or abnormal menstrual bleeding) may also be treated with the less invasive  endometrial ablation  which is an outpatient procedure in which the lining of the uterus is destroyed with heat, mechanically or by radio frequency ablation. [ 52 ]  Endometrial ablation greatly reduces or eliminates monthly bleeding in ninety percent of patients with DUB. It is not effective for patients with very thick uterine lining or uterine fibroids. [ 53 ]


Levonorgestrel intrauterine devices  are highly effective in limiting menstrual blood flow and improving other symptoms. Side effects are typically very moderate because the  levonorgestrel  (a  progestin ) is released in low concentration locally. There is now substantial evidence that Levongestrel-IUDs provide good symptomatic relief for women with fibroids. [ 54 ]


Uterine fibroids may be removed and the uterus reconstructed in a procedure called " myomectomy ". A myomectomy may be performed through an open incision, laparoscopically, or through the vagina (hysteroscopy). [ 55 ]


Uterine artery embolization  (UAE) is a minimally invasive procedure for treatment of  uterine fibroids . Under local anesthesia a catheter is introduced into the femoral artery at the groin and advanced under radiographic control into the uterine artery. A mass of microspheres or  polyvinyl alcohol  (PVA) material (an  embolus ) is injected into the uterine arteries in order to block the flow of blood through those vessels. [ 56 ]  The restriction in blood supply usually results in significant reduction of fibroids and improvement of heavy bleeding tendency. The 2012 Cochrane review comparing hysterectomy and UAE did not find any major advantage for either procedure. While UAE is associated with shorter hospital stay and a more rapid return to normal daily activities, it was also associated with a higher risk for minor complications later on. There were no differences between UAE and hysterectomy with regards to major complications. [ 57 ]


Uterine fibroids can be removed with a non-invasive procedure called  Magnetic Resonance guided Focused Ultrasound  (MRgFUS).


Prolapse may also be corrected surgically without removal of the uterus. [ 58 ]  There are several strategies that can be utilized to help strengthen pelvic floor muscles and prevent the worsening of prolapse. These include, but are not limited to, use of " kegel exercises ", vaginal pessary, constipation relief, weight management, and care when lifting heavy objects. [ 59 ]


Hysterectomy, in the literal sense of the word, means merely removal of the uterus. However other organs such as ovaries, fallopian tubes, and the cervix are very frequently removed as part of the surgery. [ 60 ]


Subtotal (supracervical) hysterectomy was originally proposed with the expectation that it may improve sexual functioning after hysterectomy, it has been postulated that removing the cervix causes excessive neurologic and anatomic disruption, thus leading to vaginal shortening,  vaginal vault prolapse , and vaginal cuff granulations. [ 62 ]  These theoretical advantages were not confirmed in practice, but other advantages over total hysterectomy emerged. The principal disadvantage is that risk of cervical cancer is not eliminated and women may continue cyclical bleeding (although substantially less than before the surgery).
These issues were addressed in a systematic review of total versus supracervical hysterectomy for  benign gynecological conditions , which reported the following findings: [ 63 ]


In the short-term, randomized trials have shown that cervical preservation or removal does not affect the rate of subsequent pelvic organ prolapse. [ 65 ]


Supracervical hysterectomy does not eliminate the possibility of having  cervical cancer  since the cervix itself is left intact and may be contraindicated in women with increased risk of this cancer; regular  pap smears  to check for  cervical dysplasia  or  cancer  are still needed. [ 66 ] [ 67 ]


Hysterectomy can be performed in different ways. The oldest known technique is vaginal hysterectomy. The first planned hysterectomy was performed by  Konrad Johann Martin Langenbeck  - Surgeon General of the Hannovarian army, although there are records of vaginal hysterectomy for prolapse going back as far as 50BC. [ 68 ]


The first abdominal hysterectomy recorded was by Ephraim McDowell. He performed the procedure in 1809 for a mother of five for a large ovarian mass on her kitchen table. [ 69 ]


In modern medicine today, laparoscopic vaginal (with additional instruments passing through ports in small abdominal incisions, close or in the navel) and total laparoscopic techniques have been developed.


Most hysterectomies in the United States are done via  laparotomy  (abdominal incision, not to be confused with  laparoscopy ). A  transverse (Pfannenstiel) incision  is made through the abdominal wall, usually above the  pubic bone , as close to the upper hair line of the individual's lower  pelvis  as possible, similar to the incision made for a  caesarean section . This technique allows  physicians  the greatest access to the reproductive structures and is normally done for removal of the entire reproductive complex. [ 70 ]  The recovery time for an open hysterectomy is 4–6 weeks and sometimes longer due to the need to cut through the  abdominal wall . Historically, the biggest problem with this technique was infections, but infection rates are well-controlled and not a major concern in modern medical practice. An open hysterectomy provides the most effective way to explore the abdominal cavity and perform complicated surgeries. Before the refinement of the vaginal and laparoscopic vaginal techniques, it was also the only possibility to achieve subtotal hysterectomy; meanwhile, the vaginal route is the preferable technique in most circumstances. [ 71 ] [ 72 ]


Vaginal hysterectomy is performed entirely through the vaginal canal and has clear advantages over abdominal surgery such as fewer complications, shorter hospital stays and shorter healing time. [ 73 ] [ 74 ]  Abdominal hysterectomy, the most common method, is used in cases such as after caesarean delivery, when the indication is cancer, when complications are expected, or surgical exploration is required.


With the development of laparoscopic techniques in the 1970s and 1980s, the "laparoscopic-assisted vaginal hysterectomy" (LAVH) has gained great popularity among  gynecologists  because compared with the abdominal procedure it is less invasive and the post-operative recovery is much faster. It also allows better exploration and slightly more complicated surgeries than the vaginal procedure. LAVH begins with  laparoscopy  and is completed such that the final removal of the uterus (with or without removing the ovaries) is via the vaginal canal. Thus, LAVH is also a total hysterectomy; the cervix is removed with the uterus. [ 75 ]  If the cervix is removed along with the uterus, the upper portion of the vagina is sutured together and called the  vaginal cuff . [ 76 ]


The "laparoscopic-assisted supracervical hysterectomy" (LASH) was later developed to remove the uterus without removing the cervix using a  morcellator  which cuts the uterus into small pieces that can be removed from the abdominal cavity via the laparoscopic ports. [ 77 ]


Total laparoscopic hysterectomy (TLH) was developed in the early 90s by Prabhat K. Ahluwalia in Upstate New York. [ 78 ]  TLH is performed solely through the laparoscopes in the abdomen, starting at the top of the uterus, typically with a uterine manipulator. The entire uterus is disconnected from its attachments using long thin instruments through the "ports". Then all tissue to be removed is passed through the small abdominal incisions.


Supracervical (subtotal) laparoscopic hysterectomy (LSH) is performed similar to the total laparoscopic surgery but the uterus is amputated between the cervix and fundus. [ 79 ]


Dual-port laparoscopy is a form of laparoscopic surgery using two 5 mm midline incisions: the uterus is detached through the two ports and removed through the vagina. [ 80 ] [ 81 ]


"Robotic hysterectomy" is a variant of laparoscopic surgery using special remotely controlled instruments that allow the surgeon finer control as well as three-dimensional magnified vision. [ 82 ]


Patient characteristics such as the reason for needing a hysterectomy, uterine size, descent of the uterus, presence of diseased tissues surrounding the uterus, previous surgery in the pelvic region, obesity, history of pregnancy, the possibility of  endometriosis , or the need for an  oophorectomy , will influence a surgeon's surgical approach when performing a hysterectomy. [ 83 ] [ needs update ]


Vaginal hysterectomy is recommended over other variants where possible for women with benign diseases. [ 71 ] [ 72 ] [ 83 ]  Vaginal hysterectomy was shown to be superior to LAVH and some types of laparoscopic surgery causing fewer short- and long-term complications, more favorable effect on sexual experience with shorter recovery times and fewer costs. [ 84 ] [ 85 ] [ 86 ]


Laparoscopic surgery offers certain advantages when vaginal surgery is not possible but also has the disadvantage of significantly longer time required for the surgery. [ 83 ] [ 73 ]


In one 2004 study conducted in the UK comparing abdominal (laparotomic) and laparoscopic techniques, laparoscopic surgery was found to cause longer operation time and a higher rate of major complications while offering much quicker healing. [ 87 ]  In another study conducted in 2014, laparoscopy was found to be "a safe alternative to laparotomy" in patients receiving total hysterectomy for endometrial cancer. Researchers concluded the procedure "offers markedly improved perioperative outcomes with a lower reoperation rate and fewer postoperative complications when the standard of care shifts from open surgery to laparoscopy in a university hospital". [ 88 ]


The abdominal technique is very often applied in difficult circumstances or when complications are expected. Given these circumstances the complication rate and time required for surgery compares very favorably with other techniques, however time required for healing is much longer. [ 83 ]


Hysterectomy by abdominal laparotomy is correlated with much higher incidence of intestinal adhesions than other techniques. [ 42 ]


Time required for completion of surgery in the eVAL trial is reported as follows: [ 87 ]


Morcellation  has been widely used especially in laparoscopic techniques and sometimes for the vaginal technique, but now appears to be associated with a considerable risk of spreading benign or malignant tumors. [ 89 ] [ 90 ]  In April 2014, the FDA issued a memo alerting medical practitioners to the risks of power morcellation. [ 91 ]


Robotic assisted surgery is presently used in several countries for hysterectomies. Additional research is required to determine the benefits and risks involved, compared to conventional laparoscopic surgery. [ 92 ]


A 2014 Cochrane review found that robotic assisted surgery may have a similar complication rate when compared to conventional laparoscopic surgery. In addition, there is evidence to suggest that although the surgery make take longer, robotic assisted surgery may result in shorter hospital stays. [ 92 ]  More research is necessary to determine if robotic assisted hysterectomies are beneficial for people with cancer. [ 92 ]


Previously reported marginal advantages of robotic assisted surgery could not be confirmed; only differences in hospital stay and cost remain statistically significant. [ 93 ] [ 94 ] [ 95 ]  In addition, concerns over widespread misleading marketing claims have been raised. [ 96 ]


In  Canada , the number of hysterectomies between 2008 and 2009 was almost 47,000. The national rate for the same timeline was 338 per 100,000 population, down from 484 per 100,000 in 1997. The reasons for hysterectomies differed depending on whether the woman was living in an urban or rural location. Urban women opted for hysterectomies due to  uterine fibroids  and rural women had hysterectomies mostly for  menstrual disorders . [ 101 ]


Hysterectomy is the second most common major surgery among women in the United States (the first is cesarean section). In the 1980s and 1990s, this statistic was the source of concern among some consumer rights groups and puzzlement among the medical community, [ 102 ]  and brought about informed choice advocacy groups like Hysterectomy Educational Resources and Services (HERS) Foundation, founded by  Nora W. Coffey  in 1982.


According to the  National Center for Health Statistics , of the 617,000 hysterectomies performed in 2004, 73% also involved the surgical removal of the ovaries. There are currently an estimated 22 million women in the United States who have undergone this procedure. Nearly 68 percent were performed for benign conditions such as endometriosis, irregular bleeding and uterine fibroids. [ 1 ]  Such rates being highest in the industrialized world has led to the controversy that hysterectomies are being largely performed for unwarranted reasons. [ 103 ]  More recent data suggests that the number of hysterectomies performed has declined in every state in the United States. From 2010 to 2013, there were 12 percent fewer hysterectomies performed, and the types of hysterectomies were more minimally invasive in nature, reflected by a 17 percent increase in laparoscopic procedures. [ 104 ]


In the UK, 1 in 5 women is likely to have a hysterectomy by the age of 60, and ovaries are removed in about 20% of hysterectomies. [ 105 ]


The number of hysterectomies in  Germany  has been constant for many years. In 2006, 149,456 hysterectomies were performed. Additionally, of these, 126,743 (84.8%) successfully benefitted the patient without incident. Women between the ages of 40 and 49 accounted for 50 percent of hysterectomies, and those between the ages of 50 and 59 accounted for 20 percent. [ 106 ]  In 2007, the number of hysterectomies decreased to 138,164. [ 64 ]  In recent years, the technique of laparoscopic or laparoscopically assisted hysterectomies has been raised into the foreground. [ 107 ] [ 108 ]


In  Denmark , the number of hysterectomies from the 1980s to the 1990s decreased by 38 percent. In 1988, there were 173 such surgeries per 100,000 women, and by 1998 this number had been reduced to 107. The proportion of abdominal supracervical hysterectomies in the same time period grew from 7.5 to 41 percent. A total of 67,096 women underwent hysterectomy during these years. [ 109 ]


Infertility in  polycystic ovary disease  (PCOS) is a hormonal imbalance in women that is thought to be one of the leading causes of  female infertility . [ 1 ] [ 2 ] [ 3 ] [ 4 ]  Polycystic ovary syndrome causes more than 75% of cases of anovulatory infertility. [ 5 ]


Not all women with PCOS have difficulty becoming pregnant. For those who do,  anovulation  is a common cause. The mechanism of this anovulation is uncertain, but there is evidence of arrested  antral follicle  development, which, in turn, may be caused by abnormal interaction of insulin and  luteinizing hormone  (LH) on  granulosa cells . [ 5 ]


Endocrine disruption may also directly decrease fertility, such as changed levels of  gonadotropin-releasing hormone , [ 6 ]   gonadotropins  (especially an increase in  luteinizing hormone ), [ 6 ] [ 7 ]   hyperandrogenemia , [ 8 ]  and  hyperinsulinemia . [ 8 ]   Gonadotropins  are released by gonadotroph cells in  pituitary gland , and these cells appear to harbor insulin receptors, which are affected by elevated insulin levels. [ 6 ]  A reason that insulin sensitizers work in increasing fertility is that they lower total insulin levels in body as metabolic tissues regain sensitivity to the hormone. This reduces the overstimulation of gonadotroph cells in pituitary. [ 6 ]


PCOS usually causes infertility associated with anovulation, and therefore, the presence of ovulation indicates absence of infertility, though it does not rule out infertility by other causes. [ citation needed ]


Ovulation may be predicted by the use of urine tests that detect the preovulatory  LH surge , called ovulation predictor kits (OPKs). However, OPKs are not always accurate when testing on women with PCOS. [ citation needed ]  A test for serum progesterone used to identify a healthy pregnancy from a miscarriage or ectopic pregnancy. Low progesterone levels are linked to miscarriages and ectopic pregnancies, both of which are considered non-viable pregnancies, whereas high progesterone levels are linked to viable pregnancies. [ 9 ]   Charting of  cervical mucus  may also be used to predict ovulation, or certain  fertility monitors  (those that track urinary hormones or changes in saliva) may be used.  Methods that predict ovulation may be used to time intercourse or insemination appropriately. Women with PCOS often ovulate at any time during their cycle, to best increase chances of conceiving it is best to have intercourse at least every other day during the 2nd and 3rd week after their period ends. [ citation needed ]


Ovulation may also be confirmed by testing for serum  progesterone  in mid-luteal phase, approximately seven days after ovulation (if ovulation occurred on the average cycle day of fourteen, seven days later would be cycle day 21).  A mid-luteal phase progesterone test may also be used to diagnose  luteal phase  defect.  Methods that confirm ovulation may be used to evaluate the effectiveness of treatments to stimulate ovulation. [ citation needed ]


Basal body temperatures  are not reliable for predicting ovulation. [ 10 ]


Management of infertility in polycystic ovary syndrome includes lifestyle modification as well as  assisted reproductive technology  such as ovulation induction, oocyte release triggering and surgery. [ citation needed ]


For overweight women with PCOS who are anovulatory, diet adjustments and weight loss are associated with resumption of spontaneous ovulation. Preliminary evidence suggests that exercise may improve menstrual regularity, pregnancy and ovulation rates, but more research is needed. [ 11 ]


For those who after weight loss still are anovulatory or for anovulatory lean women,  ovulation induction  to reverse the anovulation is the principal treatment used to help infertility in PCOS.  Letrozole  and  Clomiphene citrate  are the first-line treatment in subfertile anovulatory patients with PCOS. [ 12 ]  A  Cochrane review  showed that  letrozole  (an  aromatase inhibitor ) appears to improve live birth and pregnancy rates as compared to  clomiphene citrate . [ 13 ]  There appeared to be no difference between letrozole and laparoscopic  ovarian drilling . [ 13 ] [ 14 ]   Gonadotrophins  such as  follicle-stimulating hormone  (FSH) are, in addition to surgery, second-line treatments. [ 15 ]


For patients who do not respond to diet, lifestyle modification and ovulation induction,  in vitro fertilisation  can be performed. This usually includes  controlled ovarian hyperstimulation  with  FSH  injections, and  oocyte release triggering  with  human chorionic gonadotropin  (hCG) or a  GnRH agonist . [ citation needed ]


Surgery can be attempted in case of inefficient result with medications for ovulation induction. [ 15 ]  Though surgery is not commonly performed, the polycystic ovaries can be treated with a laparoscopic procedure called "ovarian drilling" (puncture of 4-10 small follicles with electrocautery), which often results in either resumption of spontaneous ovulations or ovulations after adjuvant treatment with clomiphene or  FSH . [ 14 ]


Previously, metformin was recommended treatment for anovulation. [ citation needed ]


A  systematic review  and  meta-analysis  in 2012 [ 16 ]  concluded that there is insufficient evidence to establish a difference between metformin and clomiphene citrate in terms of ovulation, pregnancy, live birth, miscarriage, and multiple pregnancy rates in women with PCOS and a BMI less than 32 kg/m 2 . [ 16 ]  It emphasized that a lack of superiority of one treatment is not evidence for equivalence. [ 16 ]


Another review in 2012 [ 17 ]  concluded that metformin improves  pregnancy rates  in women with PCOS when compared with placebo, and in addition to clomiphene compared with clomiphene alone, but not when compared directly with clomiphene. Also, however, it concluded that metformin does not improve  live birth rates , whether used alone or in combination with clomiphene. It therefore concluded that the benefit of metformin in the improvement of reproductive outcomes in women with PCOS is limited. [ 17 ]


The ESHRE/ASRM-sponsored Consensus workshop does not recommend metformin for ovulation stimulation. [ 18 ]  Subsequent randomized studies have confirmed the lack of evidence for adding metformin to clomiphene. [ 19 ]


When taken prior to or during IVF, there is no evidence that metformin treatment improves  live birth rate  in women with PCOS. However, metformin was found to increase clinical  pregnancy rates  and reduce the risk of  ovarian hyperstimulation syndrome  (OHSS) in women with PCOS and undergoing IVF cycles. [ 20 ]


PCOS increases the time to pregnancy but does not necessarily reduce eventual family size. [ 15 ]  It does not appear to increase  miscarriage  frequency. [ 15 ]


The following is a list of instruments that are used in modern  obstetrics  and  gynaecology . [ 1 ] [ 2 ]


The International Society for the Study of Vulvovaginal Disease  ( ISSVD ) is a non-profit organization that was founded in 1970 at the Sixth World Congress of the International Federation of Obstetricians and Gynecologists (FIGO) in New York City. It is composed of health care professionals from different areas, including, gynecologists, dermatologists, general practitioners, physiotherapist, nurse practitioners, etc. devoted to the study, investigation, and treatment of vulvovaginal diseases.


The ISSVD regularly promotes and develops terminology, classification, and guidelines concerning these conditions. These include, among others: vulvar dermatosis ( lichen sclerosus ,  lichen planus ), [ 1 ] [ 2 ]  vulvar pain ( vulvodynia ), [ 3 ] [ 4 ] [ 5 ]  vulvar intraepithelial neoplasia, [ 6 ]  etc. More recently, a guideline concerning female cosmetic genital surgery was published. [ 7 ]


The  Kahun Gynaecological Papyrus  (also  Petrie Medical Papyrus ,  Kahun Medical Papyrus ,  Lahun Medical Papyrus , or  UC32057 ) is the oldest known medical text in Egyptian history, dated to  c.  1825 BCE, during the  Twelfth Dynasty . The Papyrus addresses gynecological health concerns, pregnancy, fertility, and various treatments.


It was found at  El Lahun  ( Faiyum ,  Egypt ) by  Flinders Petrie  in 1889 [ 1 ]  and first translated by  F. Ll. Griffith  in 1893 and published in  The Petrie Papyri: Hieratic Papyri from Kahun and Gurob . [ 2 ]  It is kept in the  Petrie Museum of Egyptian Archaeology  of the  University College London . The later  Berlin Papyrus  and the  Ramesseum Papyrus IV  cover much of the same ground, often giving identical prescriptions. [ 3 ]


The text is divided into thirty-four sections, each section dealing with a specific problem and containing diagnosis and treatment; no  prognosis  is suggested. Treatments are non-surgical, comprising applying medicines to the affected body part or swallowing them. The  womb  is seen as the source of complaints manifesting themselves in other body parts, for which its fumigation is recommended, either by oils and incense or whatever the woman smells roasting, should it cause her to smell roasting. [ 4 ] [ 5 ]


In Column 3, Line 6 of the Papyrus, there are details of a contraception method involving the burning or sprinkling of crocodile dung. [ 6 ]  The Column 3, Line 6 contraception method is often misconstrued as insertion of crocodile dung against the cervix. The context of Column 3, Line 7 depicts another contraception method involving sprinkling honey and natron salt over the woman's womb to prevent pregnancy. [ 6 ]


The  knee-chest position  or  genupectoral position  is a position used in a number of medical situations including gynecological examination and surgery, lumbar spine surgery, [ 2 ] [ 3 ] [ 4 ]  repair of vesico-vaginal fistula (VVF) by Sims's saucerisation procedure, labor and delivery for which it is recommended in those with a  cord prolapse  until delivery can occur, [ 1 ]  and administering enemas. [ 5 ] [ 6 ]


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Misoprostol  is a synthetic  prostaglandin  medication used to prevent and treat  stomach and duodenal ulcers ,  induce labor , cause an  abortion , and treat  postpartum bleeding  due to poor contraction of the  uterus . [ 10 ] [ 11 ]  It is taken  by mouth  when used to prevent gastric ulcers in people taking  nonsteroidal anti-inflammatory drugs  (NSAID). [ 11 ]  For abortions it is used by itself or in conjunction with  mifepristone  or  methotrexate . [ 12 ]  By itself, effectiveness for abortion is between 66% and 90%. [ 13 ] [ 14 ]  For labor induction or abortion, it is taken by mouth, dissolved in the mouth, or  placed in the vagina . [ 12 ] [ 15 ] [ 16 ] [ 17 ] [ 18 ]  For postpartum bleeding it may also be  used rectally . [ 19 ]


Common side effects include  diarrhea  and abdominal pain. [ 11 ]  It is in  pregnancy category  X, meaning that it is known to result in negative outcomes for the fetus if taken during  pregnancy . [ 11 ]  In rare cases,  uterine rupture  may occur. [ 11 ]  It is a  prostaglandin analogue —specifically, a synthetic  prostaglandin E 1  (PGE 1 ). [ 11 ]


Misoprostol was developed in 1973. [ 20 ]  It is on the  World Health Organization's List of Essential Medicines . [ 21 ]  It is available as a  generic medication . [ 11 ]


Misoprostol is used for the prevention of  NSAID -induced gastric ulcers. It acts upon gastric  parietal cells , inhibiting the secretion of  gastric acid  by  G-protein coupled receptor -mediated inhibition of  adenylate cyclase , which leads to decreased intracellular  cyclic AMP  levels and decreased  proton pump  activity at the  apical  surface of the parietal cell. Misoprostol is sometimes coprescribed with NSAIDs to prevent their common adverse effect of  gastric ulceration  (e.g., with  diclofenac  in  Arthrotec ). [ citation needed ]


However, even in the treatment of NSAID-induced ulcers,  omeprazole  proved to be at least as effective as misoprostol, [ 22 ]  but was significantly better tolerated, so misoprostol should not be considered a first-line treatment. Misoprostol-induced diarrhea and the need for multiple daily doses (typically four) are the main issues impairing compliance with therapy. [ medical citation needed ]


Misoprostol is commonly used for  labor induction . It causes  uterine  contractions and the ripening ( effacement  or thinning) of the  cervix . [ 23 ]  It can be less expensive than the other commonly used ripening agent,  dinoprostone . [ 24 ]


Oxytocin  has long been used as the standard agent for labor induction, but does not work well when the cervix is not yet ripe. Misoprostol also may be used in conjunction with oxytocin. [ 24 ]


Between 2002 and 2012, a misoprostol vaginal insert was studied, and was approved in the EU. [ 25 ] [ 26 ] [ 27 ]  It was not approved for use in the United States, and the US FDA still considers cervical ripening and labor induction to be outside of the approved uses for misoprostol. [ 28 ] [ 29 ]


When administered prior to  myomectomy  in women with uterine fibroids, misoprostol reduces operative blood loss and requirement of blood transfusion. [ 30 ]


Misoprostol is used either alone or in conjunction with another medication ( mifepristone  or  methotrexate ) for  medical abortions  as an alternative to  surgical abortion . [ 31 ]  Medical abortion has the advantage of being less invasive, and more autonomous, self-directed, and discreet. It is preferred by some women because it feels more natural, as the drugs induce a miscarriage. [ 32 ]  It is also more easily accessible in places where abortion is illegal. [ 33 ]  The  World Health Organization  (WHO) provides clear guidelines on the use, benefits and risks of misoprostol for abortions. [ 34 ]


Misoprostol is most effective when it is used in combination with methotrexate or mifepristone (RU-486). [ 35 ]  Mifepristone blocks signaling by  progesterone , causing the uterine lining to degrade, the blood vessels of the  cervix  and  uterus  to dilate and causing uterine contraction, similar to a  menstrual period , which causes the embryo to detach from the uterine walls. [ 36 ]  Misoprostol then dilates the cervix and induces muscle contractions which clear the uterus. [ citation needed ]  Misoprostol alone is less effective (typically 88% up to eight-weeks gestation). It is not inherently unsafe if medically supervised, but 1% of women will have heavy bleeding requiring medical attention, some women may have  ectopic pregnancy , and the 12% of pregnancies that continue after misoprostol failure are more likely to have birth defects and are usually followed up with a more effective method of abortion. [ 37 ]


Most large studies recommend a protocol for the use of misoprostol in combination with mifepristone. [ 38 ] [ 39 ]  Together they are effective in around 95% for early pregnancies. [ 40 ]  Misoprostol alone may be more effective in earlier gestation. [ 41 ]


Misoprostol can also be used to  dilate the cervix  in preparation for a surgical abortion, particularly in the second trimester (either alone or in combination with  osmotic dilators ). [ citation needed ]


Misoprostol by mouth is the least effective treatment for producing complete abortion in a period of 24 hours due to the liver's  first-pass effect  which reduces the  bioavailability  of the misoprostol. Vaginal and sublingual routes result in greater efficacy and extended duration of action because these routes of administration allow the drug to be directly absorbed into circulation by bypassing the liver first-pass effect. [ 42 ] [ 17 ] [ 18 ]


Hematocrit  or Hb tests and Rh testing are recommended before use for abortion confirmation of pregnancy. [ 43 ]  Following use, it is recommended that people attend a follow-up visit 2 weeks after treatment. If used for treatment of complete abortion, a pregnancy test, physical examination of the uterus, and ultrasound should be performed to ensure success of treatment. Surgical management is possible in the case of failed treatment. [ 42 ]


Misoprostol may be used to complete a  miscarriage  or  missed abortion  when the body does not expel the embryo or fetus on its own. Compared to no medication or placebo, it could decrease the time to complete expulsion. [ 44 ]  Use of a single dose of misoprostol vaginally or buccally is preferred, with additional doses as needed. It also can be used in combination with mifepristone, with a similar regimen to medical abortion. [ 17 ] [ 18 ]


Misoprostol is regularly used in some Canadian hospitals for labour induction for fetal deaths early in pregnancy, and for termination of pregnancy for fetal anomalies. A low dose is used initially, then doubled for the remaining doses until delivery. In the case of a previous Caesarian section, however, lower doses are used.


Misoprostol is also used to prevent and treat  post-partum bleeding . Orally administered misoprostol was marginally less effective than  oxytocin . [ 45 ]  The use of rectally administered misoprostol is optimal in cases of bleeding; it was shown to be associated with lower rates of side effects compared to other routes. Rectally administered misoprostol was reported in a variety of case reports and randomised controlled trials. [ 46 ] [ 47 ]  However, it is inexpensive and thermostable (thus does not require refrigeration like oxytocin), making it a cost-effective and valuable drug to use in the developing world. [ 48 ]  A randomised control trial of misoprostol use found a 38% reduction in maternal deaths due to  post partum  haemorrhage in resource-poor communities. [ 49 ]  Misoprostol is recommended due to its cost, effectiveness, stability, and low rate of side effects. [ 50 ]  Oxytocin must also be given by injection, while misprostol can be given orally or rectally for this use, making it much more useful in areas where nurses and physicians are less available. [ 51 ]


In women with prior caesarean section or prior failure of insertion of an intrauterine contraceptive device, pre-procedure administration of misoprostol reduces the rate of failure of insertion of intrauterine contraceptive device. However, due to a higher rate of adverse effects, routine use of misoprostol for this purpose in other women is not supported by the data. [ 52 ]


For  cervical ripening  in advance of endometrial biopsy to reduce the need for use of a tenaculum or cervical dilator. [ citation needed ]


There is limited evidence supporting the use of misoprostol for the treatment of  trigeminal neuralgia  in patients with  multiple sclerosis . [ 53 ] [ 54 ]


The most commonly reported  adverse effect  of taking misoprostol by mouth for the prevention of stomach ulcers is  diarrhea . In clinical trials, an average 13% of people reported diarrhea, which was dose-related and usually developed early in the course of therapy (after 13 days) and was usually self-limiting (often resolving within 8 days), but sometimes (in 2% of people) required discontinuation of misoprostol. [ 55 ]


The next most commonly reported adverse effects of taking misoprostol by mouth for the prevention of gastric ulcers are:  abdominal pain ,  nausea ,  flatulence ,  headache ,  dyspepsia ,  vomiting , and  constipation , but none of these adverse effects occurred more often than when taking  placebos . [ 55 ]


There are increased side effects with sublingual or oral misoprostol, compared to a low dose (400 μg) vaginal misoprostol. However, low dose vaginal misoprostol was linked with low complete abortion rate. [ 42 ]  The study concluded that sublingually administered misoprostol dosed at 600 μg or 400 μg had greater instances of fever and diarrhea due to its quicker onset of action, higher peak concentration and bioavailability in comparison to vaginal or oral misoprostol. [ 42 ]


For the indication of medical abortion, bleeding and cramping is commonly experienced after administration of misoprostol. Bleeding and cramping is likely to be greater than that experienced with menses, however, emergency care is advised if bleeding is excessive. [ 43 ]


Misoprostol should not be taken by pregnant women with wanted pregnancies to reduce the risk of NSAID-induced gastric ulcers because it increases uterine tone and contractions in pregnancy, which may cause partial or complete abortions, and because its use in pregnancy has been associated with birth defects. [ 55 ] [ 56 ]


All cervical ripening and induction agents can cause  uterine hyperstimulation , which can negatively affect the blood supply to the fetus and increases the risk of complications such as uterine rupture. [ 57 ]  Concern has been raised that uterine hyperstimulation that occurs during a misoprostol-induced labor is more difficult to treat than hyperstimulation during labors induced by other drugs. [ 58 ]  Because the complications are rare, it is difficult to determine if misoprostol causes a higher risk than do other cervical ripening agents. One estimate is that it would require around 61,000 people enrolled in randomized controlled trials to detect a difference in serious fetal complications and about 155,000 people to detect a difference in serious maternal complications. [ 59 ]


It is recommended that medical treatment for  missed abortion  with misoprostol should only be considered in people without the following contraindications: suspected ectopic pregnancy, use of non-steroidal drugs, signs of pelvic infections or sepsis, unstable hemodynamics, known allergy to misoprostol, previous caesarean section, mitral stenosis, hypertension, glaucoma, bronchial asthma, and remote areas without a hospital nearby. [ 42 ]


Misoprostol, a  prostaglandin analogue , binds to myometrial cells to cause strong myometrial contractions leading to expulsion of tissue. This agent also causes cervical ripening with softening and dilation of the cervix. Misoprostol binds to and stimulates  prostaglandin EP 2  receptors ,  prostaglandin EP 3  receptor  and  prostaglandin EP 4  receptor  but not  prostaglandin EP 1  receptor  and therefore is expected to have a more restricted range of physiological and potentially toxic actions than prostaglandin E 2  or other analogs which activate all four prostaglandin receptors. [ 60 ]


In August 2000, a letter from  G.D. Searle, LLC , the inventor of the drug, [ 61 ] [ 62 ]  generated controversy by warning against its use by pregnant women because of its ability to induce abortion, citing reports of maternal and fetal deaths when it was used to induce labor. [ 63 ]  The  American College of Obstetricians and Gynecologists  holds that substantial evidence supports the use of misoprostol for induction of labor, a position it reaffirmed in response to the Searle letter. [ 64 ]  It is on the  World Health Organization's List of Essential Medicines . [ 21 ]


A vaginal form of the medication is sold in the EU under the names Misodel [ 65 ]  and Mysodelle [ 66 ]  for use in labor induction. [ medical citation needed ]


Misoprostol is used for  self-induced abortions  in Brazil, where  black market  prices exceed US$100 per dose. Illegal medically unsupervised misoprostol abortions in Brazil are associated with a lower complication rate than other forms of illegal self-induced abortion, but are still associated with a higher complication rate than legal, medically supervised surgical and medical abortions. Failed misoprostol abortions are associated with birth defects in some cases. [ 67 ] [ 68 ] [ 69 ] [ 70 ] [ 71 ]  Low-income and immigrant populations in  New York City  have also been observed to use self-administered misoprostol to induce abortions, as this method is much cheaper than a surgical abortion (about $2 per dose). [ 72 ]  The drug is readily available in Mexico. [ 73 ]  Use of misoprostol has also increased in Texas in response to increased regulation of abortion providers. [ 74 ]  Following the United States Supreme Court decision of  Dobbs v. Jackson Women's Health Organization , many states restricted access to legal abortion services, including medication abortion using misoprostol. As a result of these restrictions, it was reported that there was an increase in self-managed abortions by women in the United States. Many women purchased the pills from overseas online pharmacies or obtained misoprostol from Mexico. [ 75 ]


Morning sickness , also called  nausea and vomiting of pregnancy  ( NVP ), is a  symptom of pregnancy  that involves  nausea  or  vomiting . [ 1 ]  Despite the name, nausea or vomiting can occur at any time during the day. [ 2 ]  Typically the symptoms occur between the 4th and 16th  weeks of pregnancy . [ 2 ]  About 10% of women still have symptoms after the 20th week of pregnancy. [ 2 ]  A severe form of the condition is known as  hyperemesis gravidarum  and results in weight loss. [ 1 ] [ 6 ]


The cause of morning sickness is unknown but may relate to changing levels of the hormone  human chorionic gonadotropin . [ 2 ]  Some have proposed that morning sickness may be useful from an  evolutionary  point of view. [ 1 ]  Diagnosis should only occur after other possible causes have been ruled out. [ 3 ]   Abdominal pain , fever, or  headaches  are typically not present in morning sickness. [ 1 ]


Morning sickness affects about 70–80% of all pregnant women to some extent. [ 4 ] [ 5 ]  About 60% of women experience vomiting. [ 2 ]  Hyperemesis gravidarum occurs in about 1.6% of pregnancies. [ 1 ]  Morning sickness can negatively affect  quality of life , result in decreased ability to work while pregnant, and result in health-care expenses. [ 3 ]  Generally, mild to moderate cases have no effect on the fetus, and most severe cases also have normal outcomes. [ 1 ]  Some women choose to have an  abortion  due to the severity of symptoms. [ 1 ]  Complications such as  Wernicke encephalopathy  or  esophageal rupture  may occur, but very rarely. [ 1 ]


Taking  prenatal vitamins  before pregnancy may decrease the risk. [ 3 ]  Specific treatment other than a bland diet may not be required for mild cases. [ 2 ] [ 6 ] [ 3 ]  If treatment is used the combination of  doxylamine and pyridoxine  is recommended initially. [ 3 ] [ 4 ]  There is limited evidence that  ginger  may be useful. [ 3 ] [ 7 ]  For severe cases that have not improved with other measures  methylprednisolone  may be tried. [ 3 ]   Tube feeding  may be required in women who are losing weight. [ 3 ]


About 66% of women have both nausea and vomiting while 33% have just nausea. [ 1 ]  Symptoms of both nausea and vomiting will normally climax around 10 and 16 weeks of pregnancy, subsiding around 20 weeks. [ 8 ]  However, after around 22 weeks, up to 10% of women continue to have lingering symptoms. [ 8 ]


The cause of morning sickness is unknown but may relate to changing levels of estrogen and the hormone  human chorionic gonadotropin . [ 2 ] [ 9 ]  Some have proposed that morning sickness may be useful from an  evolutionary  point of view -it may protect both the pregnant woman and the developing embryo just when the fetus is most vulnerable. [ 1 ]  Diagnosis should only occur after other possible causes have been ruled out. [ 3 ]   Abdominal pain , fever, or  headaches  are typically not present in morning sickness. [ 1 ]


Nausea and vomiting may also occur with  molar pregnancy . [ 10 ]


Morning sickness is related to diets low in cereals and high in sugars, oilcrops, alcohol and meat. [ 11 ]


Morning sickness may be an  evolved trait  that protects the fetus against  toxins  ingested by the mother. Biologist Margie Profet believes that nausea and food aversions during pregnancy evolved to impose dietary restrictions on the mother in the early weeks of pregnancy, when the mother and the embryo are most immunologically vulnerable, to minimize fetal exposure to toxins such as mutagens and teratogens. [ 15 ]  By reducing exposure to such chemicals, morning sickness reduces impairments on normal embryonic development and increases the reproductive success of the mother and survival success of both the mother and her offspring. Evidence in support of this theory includes: [ 16 ] [ 11 ]


Women who have  no  morning sickness are more likely to  miscarry . [ 17 ] [ 18 ]  This may be because such women are more likely to ingest substances that are harmful to the fetus. [ 19 ]


In addition to protecting the fetus, morning sickness may also protect the mother.  A pregnant woman's  immune system  is suppressed during pregnancy, presumably to reduce the chances of  rejecting  tissues of her own offspring. [ 20 ]  Because of this, animal products containing  parasites  and harmful bacteria can be especially dangerous to pregnant women. There is evidence that morning sickness is often triggered by animal products including meat and fish. [ 21 ]


If morning sickness is a defense mechanism against the ingestion of toxins, the prescribing of  anti-nausea medication  to pregnant women may have the undesired  side effect  of causing birth defects or miscarriages by encouraging harmful dietary choices. [ 16 ]


Also, morning sickness is a defense mechanism because when analyzing embryonic growth, several critical periods are identified in which there is mass proliferation and cell division resulting in the development of the heart and central nervous system that are very sensitive. In that period, the fetus is most at risk from damage to toxins and mutagens. These developments occur through week 6-18 which is in the same time frame in which the most nausea and vomiting of pregnancy (NVP) occurs. This relationship between the time at which the embryo is most susceptible to toxins lines up exactly with when the most severe NVP symptoms are seen, suggesting that this NVP is an evolutionary response developed in the mother, to indicate the sensitivity of the fetus hence making her wary to her health and in turn protecting the fetus. [ 21 ]


There is a lack of good evidence to support the use of any particular intervention for morning sickness. [ 7 ]


A number of  antiemetics  are effective and safe in pregnancy including:  pyridoxine/doxylamine ,  antihistamines  (such as  diphenhydramine ),  metoclopramide , and  phenothiazines  (such as  promethazine ). [ 22 ] [ 23 ]  With respect to effectiveness it is unknown if one is superior to another. [ 22 ]  In the United States and Canada, the doxylamine-pyridoxine combination (as Diclegis in US and Diclectin in Canada) is the only approved  pregnancy category  "A" prescription treatment for nausea and vomiting of pregnancy. [ 23 ]


Ondansetron  may be beneficial, but there are some concerns regarding an association with  cleft palate , [ 24 ]  and there is little high quality data. [ 22 ]   Metoclopramide  is also used and relatively well tolerated. [ 25 ]  Evidence for the use of  corticosteroids  is weak. [ 26 ]


A recent review of studies has found  acupuncture  to be safe and effective for NVP. [ 27 ]   Acupressure  applied at the acupuncture point PC6 with finger pressure or a nausea band has some evidence of effectiveness, [ 28 ] [ 29 ] [ 7 ]  as does auricular (ear acupuncture). [ 7 ]


Some studies support the use of  ginger , but overall the evidence is limited and inconsistent. [ 3 ] [ 7 ] [ 9 ] [ 30 ]  Safety concerns have been raised regarding its  anticoagulant  properties. [ 9 ] [ 31 ] [ 32 ] [ 33 ]


In the late 1950s and early 1960s, the use of  thalidomide  in 46 countries by women who were pregnant or who subsequently became pregnant resulted in the "biggest man‐made medical disaster ever," with more than 10,000 children born with a range of severe deformities, such as  phocomelia , as well as thousands of miscarriages. [ 34 ] [ 35 ]


Thalidomide was introduced in 1953 as a tranquilizer, and was later marketed by the German pharmaceutical company  Chemie Grünenthal  under the  trade name   Contergan  as a medication for  anxiety ,  trouble sleeping , "tension", and morning sickness. [ 36 ] [ 37 ]  It was introduced as a sedative and medication for morning sickness without having been tested on pregnant women. [ 38 ]  While initially deemed to be safe in pregnancy, concerns regarding birth defects were noted in 1961, and the medication was removed from the market in Europe that year. [ 36 ] [ 39 ]


The  Mothers of Gynecology Monument  by  Michelle Browder  was unveiled in  Montgomery, Alabama , on September 24, 2021. [ 1 ] [ 2 ]  It is located at 17 Mildred Street, near the  National Memorial for Peace and Justice , and is 15 feet (4.6 m) tall. [ 3 ]  The statues depict  Anarcha Westcott , Betsey, and Lucy, three enslaved women who were patients of controversial doctor and "father of gynecology"  J. Marion Sims , whose office was nearby. [ 4 ]  The statues were made from discarded metal objects—the artist asked for contributions from the public—"to symbolize how Black women have been treated and to demonstrate the beauty in the broken and discarded." [ 3 ]


On February 16, 2022, the Medical Association of the State of Alabama visited the monument and presented Browder with a $15,000 donation. [ 5 ] [ 6 ]


Nipple pigmentation  or  areolar pigmentation  is  pigmentation  (darkening) of the  nipple  or  areola . It is dose-dependently induced as an effect of  estrogens  and can occur normally during  pregnancy  and  breastfeeding  or as a  side effect  of  high-dose estrogen  therapy. [ 1 ] [ 2 ]


Hyperkeratosis  is a condition in which there is a development of a warty thickening and  pigmentation  of the nipple, areola or both. It is an uncommon skin condition, with only 150 reported cases to date. It may occur in both genders. However, 80% of the cases have been reported in females primarily within the  third decade of life . Since the skin lesions are mostly asymptomatic which do not require urgent medical attention most of the times, the reported cases may be underestimated than the actual prevalence. The  pathophsiology  of the condition is unclear. In women, it usually occurs after  puberty , aggravates during pregnancy and subsides after delivery. Some cases have been reported in individuals who underwent  estrogen therapy .  Although, it is a benign condition, it is associated with cosmetic concerns and  may also cause problems during breastfeeding. Hyperkeratosis may last indefinitely, if left untreated. The treatment consists of surgical  methods or topical medications. [ 3 ]


Noninvasive prenatal testing  ( NIPT ) is a method used to determine the risk for the fetus being born with certain  chromosomal abnormalities , such as  trisomy 21 ,  trisomy 18  and  trisomy 13 . [ 1 ] [ 2 ] [ 3 ]  This testing analyzes small DNA fragments that circulate in the blood of a pregnant woman. [ 4 ]  Unlike most DNA found in the nucleus of a cell, these fragments are not found within the cells, instead they are free-floating, and so are called  cell free fetal DNA  (cffDNA). These fragments usually contain less than 200 DNA building blocks (base pairs) and arise when cells die, and their contents, including DNA, are released into the bloodstream. CffDNA derives from placental cells and is usually identical to fetal DNA. Analysis of cffDNA from  placenta  provides the opportunity for early detection of certain chromosomal abnormalities without harming the fetus. [ 5 ]


Non-Invasive Prenatal Testing, or NIPT, is a simple blood draw that screens for chromosomal abnormalities of a fetus while still in utero. When this screening was first performed it was used to determine the sex of a fetus, now it is also used to find aneuploidies in fetal DNA. [ 6 ]  Aneuploidies are disorders in which a fetus has the incorrect number of chromosomes, either too many or not enough. [ 7 ]  The use of  ultrasound  and biochemical markers to detect aneuploidies is usually done in the first and / or second trimester of pregnancy. [ 8 ]  Aneuploidies is when a fetus retains an abnormal amount of haploid cells from their parents. However, both of these approaches have a high rate of false positive results of 2–7%. [ 9 ]  If these tests indicate an increased risk of aneuploidy, then invasive diagnostic testing is used, such as  amniocentesis  or  chorionic villus sampling . Many women, however, feel uncomfortable with the invasive testing, because of the risk associated with miscarriage, which is around 0.5%. [ 10 ]  Noninvasive prenatal testing is an intermediate step between prenatal screening and invasive diagnostic testing. The only physical risk associated with the procedure is the blood draw and there is no risk of miscarriage. [ 11 ]


NIPT works by sampling cffDNA, which are small fragments of fetal blood DNA that comes from the placenta of the mother and flows in her blood vessels. Circulating cffDNA can be detected in maternal blood between the 5th and the 7th week of  gestational age , [ 12 ]  however more fetal DNA is available for analysis usually after 10 weeks, because the amount of fetal DNA increases over time. [ 13 ]  cffDNA, RNA and intact fetal cells can all be used to assess the genetic status of the fetus non-invasively. Recent advances in DNA sequencing, such as  massive parallel sequencing  (MPS) and  digital polymerase chain reaction  (PCR), are currently under exploration for the detection of chromosomal aneuploidies via NIPT/NIPS. [ 14 ] [ 15 ] [ 16 ] [ 17 ]


Since 2014, noninvasive testing has identified aneuploidies in chromosomes 13, 16, 18, 21, 22, X and Y, including  Down syndrome  (caused by trisomy 21),  Edwards syndrome  (caused by trisomy 18),  Patau syndrome  (caused by trisomy 13), as well as sex chromosome aneuploidies, such as Turner syndrome (45, X) and Klinefelter syndrome (47, XXY). [ 18 ] [ 19 ] [ 20 ]  These methods of cffDNA sequencing have sensitivity and specificity rates greater than 99% in identifying Trisomy 21. Sensitivity and specificity rates are lower for other aneuploidies, such as trisomy 18 (97–99% and > 99%, respectively), trisomy 13 (87–99% and > 99%, respectively), and 45, X (92–95% and 99%, respectively). The low false positive rate (1–3%) is one of the advantages of NIPT which allows pregnant women to avoid invasive procedures. [ 21 ]  In the UK the Advertising Standards Authority has stated that one should not quote “Detection Rate” figures unless the figures are accompanied by (i.e. alongside)a robust "Positive Predictive Value" figure; and a clear explanations about what both figures mean. [ 22 ]


NIPT can determine paternity and may be able to determine fetal sex earlier in gestation than previous tests such as ultrasounds. It is recommended that the test be performed towards the end of the first trimester to the beginning of the second trimester, when there is enough cffDNA circulating in the mother's bloodstream to be detectable. [ 23 ]  If the test is performed too early the test is more likely to yield a false negative result because there is not enough cffDNA in the sample. False negative results for NIPT would indicate that the fetus does not have a genetic abnormality when it actually does. [ 24 ] [ 25 ]  It is also used to determine fetal Rhesus D, which can prevent mothers who are Rhesus D negative from undergoing unnecessary prophylactic treatment. [ 26 ] [ 27 ]  Finally, it is used to detect  genetic mutations , such as  duplications  or  microdeletions , including 1p, 5p, 15q, 22q, 11q, 8q, and 4p. The sensitivity and specificity of these tests, however, for most have not yet been validated. [ 11 ]


The  Natera  SMART study however has shown that most cases of 22q11.2 deletion can be detected using SNP based  NIPT/NIPS  (Panorama) including smaller nested deletions whilst still maintaining a low false positive rate. [ 28 ]  Single nucleotide polymorphism (SNP) NIPT can also detect Triploidy and can differentiate between maternal and "fetal" DNA which reduces the redraw rate and allows determination of gender for each fetus in twin pregnancies and can be done from 9 weeks of pregnancy. [ 29 ] [ 30 ]


For micro deletions such as  DiGeorge syndrome , 1p36 deletion,  Cri-du-chat syndrome ,  Wolf-Hirschhorn syndrome ,  Prader-Willi  and  Angelman  syndromes, positive results can be incorrect as much as 85% of the time, according to a New York Times investigation. [ 31 ]


When a woman is pregnant the placenta will release small DNA fragments into her bloodstream (cffDNA) which can be sampled without disturbing the fetus in utero with an invasive procedure. [ 7 ]  The NIPT testing uses chromosomal next generation sequencing to track the variation in fetal genes that could be signs of abnormalities. [ 32 ]  A blood sample is taken from the perspective mother and the cffDNA is analyzed for several aneuploidies and other genetic markers. Once the blood test is obtained it is taken to the lab where a PCR test is performed to detect single fetal nucleotide variations.


NIPT is used to detect an array of genetic disorders including Trisomy 13 (Patau Syndrome), Trisomy 18 (Edward's Syndrome), and Trisomy 21 (Down Syndrome). [ 32 ]  It can also be used to determine the sex and paternity of a child while still in utero. The most common genetic condition tested for is Trisomy 21. The test can also detect disorders that affect the sex-linked chromosomes such as Turner's Syndrome, Triple X Syndrome, and Klinefelter Syndrome. NIPT can also detect congenital heart disease such as atrioventricular septal defect, and this disease can also be a side effect in the conditions mentioned above. [ 33 ]


The NIPT test does not put the mother or the fetus in any type of danger compared to the other invasive tests that are available, making it the safest option for prenatal testing. Studies have found that the in the instance of detecting Trisomy 21 has a reliability value of 99.2%, which makes NIPT more reliable than other tests than are performed to determine the presence of these genetic disorders. [ 7 ]  However, the test does have limitations. If the test is performed early during the first trimester there is a chance that it can yield false negative or positive results, and false positive results may cause unnecessary worry for prospective parents. Another concerning factor could be the cost to have these tests conducted, because some insurance companies will not cover the cost of the test if it's not deemed medically necessary. NIPT also may not be available in certain areas, limiting access to the test in these areas. There is also an ethical debate surrounding NIPT and eugenics, because the results of this test can lead to parents opting for abortion if the fetus tests positive for a genetic disorder. [ 34 ]


The  Nugent Score  is a  Gram stain  scoring system for vaginal swabs to diagnose bacterial  vaginosis (BV) . The Nugent score is calculated by assessing for the presence of large  Gram-positive   rods  ( Lactobacillus  morphotypes; decrease in  Lactobacillus  scored as 0 to 4), small Gram-variable rods ( Gardnerella vaginalis  morphotypes; scored as 0 to 4), and curved Gram-variable rods ( Mobiluncus  spp. morphotypes; scored as 0 to 2). A score of 7 to 10 is consistent with bacterial vaginosis without culture. The Nugent Score is now rarely used by physicians due to the time it takes to read the slides and requires the use of a trained microscopist. [ 1 ]  Bacterial vaginosis diagnosis is done by evaluating the pH, the presences of   Lactobacillus  spp.  versus a mixed flora consisting of  Gardnerella vaginalis ,  Bacteroides  spp,  Mobiluncus  spp, and  Mycoplasma hominis .  The Amsel Criteria for bacterial vaginosis includes pH, evaluating the presence of clue cells, white discharge and an odor of amines after mixing with KOH. [ 2 ]


Prior to the development of Nugent score, assessment of bacterial vaginosis was based on culturing  G. vaginalis,  examining a  gram stain  of  vaginal discharge  and  gas chromatography . [ 3 ]


A score of 0-10 is generated from combining three other scores.  The scores are as follows: [ 3 ]


At least 10–20 high power (1000× oil immersion) fields are counted and an average determined.


Lactobacillus morphotypes — average per high powered (1000× oil immersion) field. View multiple fields.


Gardnerella  /  Bacteroides  morphotypes — average per high powered (1000× oil immersion) field. View multiple fields.


Curved Gram variable rods — average per high powered (1000× oil immersion) field. View multiple fields (note that this factor is less important — scores of only 0–2 are possible)


The scoring system was proposed by Robert P Nugent in 1991. In the study, vaginal swabs were obtained from pregnant women. [ 3 ]


An  obstetric hospitalist  (Ob hospitalist or OB/GYN hospitalist) is an  obstetrician  and  gynaecologist   physician  who is either employed by a  hospital  or a  physician practice  and whose duties include providing care for  laboring  patients and managing obstetric  emergencies . Some obstetrics  hospitalists  also have responsibilities including  resident  and medical student teaching; providing backup support for  family practitioners  and  nurse midwives , assisting private physicians with  surgery , assuming care for ob-gyn patients unassigned to a physician and providing vacation coverage for the private practicing physician. [ 1 ]


The first known obstetrics hospitalist program started in 1989 at  Alta Bates Medical Center  in  Berkeley ,  California . [ citation needed ]  The number of obstetric hospitalist programs grew exponentially over the subsequent years, increasing from 61 known programs in 2009 to over 245 programs in 2016. [ citation needed ]


The term "hospitalist" was first used in a 1996  New England Journal of Medicine  article by  Robert Wachter  and Lee Goldman. [ 2 ]  They described a "new breed" of  inpatient  medical specialist who would be responsible for management of hospital patients. The hospitalists are typically physicians who spend more than 25% of their time caring for hospitalized  patients .  They have the responsibility for a patient's in-hospital care, similar to the way that  primary care physicians  are responsible for outpatient care. Wachter & Goodman theorized that doctors who practiced inpatient medicine exclusively would provide care that was more efficient, of better quality, at a lower cost, and ultimately would provide better value for patients. [ 2 ]


Since the mid-1990s, the hospitalist movement has experienced significant growth. In 2012, more than 30,000 hospitalists were staffed at 70% of the hospitals in the US. [ 3 ]  Originally, the hospitalist community was primarily made up of general  internists , family physicians and  pediatricians .  Specialty-care  hospitalists soon followed, including  neurologists  (neurohospitalists), surgeons (surgicalists),  psychiatric  hospitalists,  orthopedic  hospitalists,  dermatology  hospitalists and obstetricians (termed laboriousts, ob hospitalists or obgyn hospitalists).


The term  laborioust  was coined in an article written in 2002 by Louis Weinstein, MD in the  American Journal of Obstetrics and Gynecology . Weinstein focused on the demands obstetricians face every day; from their offices, multiple telephone calls and patients in the hospital. In the article he wrote, "To improve the survivability and well-being of the obstetrician, I propose a new focus of practice for the practitioner, to be called the laborist. The laborist position is perfect for the individual who desires to practice obstetrics but who wishes to avoid the aspects of an office practice. This individual is available on the delivery floor to provide prompt, continuous, and efficient care to the laboring patient or to the patient who needs evaluation for an obstetric problem." [ 4 ]


The main function of the obstetrics hospitalists is to intercede as needed to ensure  patient safety  and quality care in the labor and delivery unit. The scope of care can extend to the  antepartum ,  postpartum , and  emergency  units.  Specific roles of the obstetric hospitalist include inpatient consultations, triaging patients for private physicians, monitoring laboring patients, providing care as required, and responding to  precipitous deliveries  and emergencies. [ 5 ]


Obstetric hospitalist programs throughout the country have taken various forms, including programs where physicians on the medical staff voluntarily take 12- or 24-hour shifts to provide continuous coverage for their labor and delivery unit. One such program was developed in response to a hospital requirement that physicians be present during the first 30 minutes after an  epidural  has been placed. Relieving the medical staff of this responsibility, as well as having a physician present and available to respond to patient emergencies, was a significant physician satisfier, and far outweighed the inconvenience of having to spend the night in the hospital once a month. [ 6 ]


Other voluntary programs provide limited labor and delivery coverage during the hours of the day or night that historically have had the greatest volume of unattended deliveries or untoward patient outcomes because physicians are not present in the hospital. Some obstetrics hospitalist programs consist of hospital-employed physicians who staff labor and delivery 24 hours a day.  Hospitals now have the option of setting up a group of hospitalists under contract or working with existing corporations that provide physician staffing in various specialties [ 7 ] [ 8 ]  or that exclusively provide obstetrics hospitalist staffing and program development. [ 9 ] [ 10 ]


The obstetric hospitalist specialty is further enhanced by the Society of Ob/Gyn Hospitalists. This group, established in 2011, is "dedicated to enhancing the safety and quality of obstetric and gynecologic hospital medicine by promoting excellence through education, coordination of hospital teams, and collaboration with health care delivery systems." [ 11 ]  The society members explained their origin as a response to the need for leadership, a sharper focus on patient safety and quality and increasing costs.  In the February 2016  Obstetrics and Gynecology  journal  the society members also suggest that early research shows obstetric hospitalists improve patient safety and the quality of care in labor and delivery units. [ 12 ]


In the traditional patient care model,  nurses  have been the front line in the labor and delivery unit with patients until the private physician arrives for a delivery. The physician communicates orders to the nurses when they are contacted about the patient usually via telephone. The nurse and physician generally discuss a plan of care and estimate a delivery time so the physician can come to the hospital in a timely manner.  If a patient emergency occurs prior to the arrival of the physician the nurse is responsible for care of the patient.  This has been the way most labor and delivery units have been managed since women began laboring and delivering in hospitals.


The arrival of the obstetrics hospitalists has changed this traditional pattern of care.  In a hospital system with a full-time obstetric hospitalist program an obstetrician is available in the hospital 24 hours a day.  Obstetric hospitalists are in the unique position of having more experience with obstetrical emergencies than the average private obstetrician because they are present for most of the complicated or emergency cases.  This experience increases the quality of the care they provide.  In this new model, pregnant patients have access to immediate obstetrical care and private obstetricians have an onsite partner who can offer  second opinions  and assistance with complicated or  high risk cases .  This model also provides the hospital staff with a physician available to offer immediate support,  education  and patient care.  The  hospital administration  has a tangible system in place that directly supports quality care and patient satisfaction.


Obstetric hospitalist programs play an important role in evolving health care delivery systems that focus on strategies that increase safety and satisfaction while reducing risk and costs. [ 5 ]


Obstetrics and gynaecology  (also spelled as  obstetrics and gynecology ; abbreviated as  Obs and Gynae ,  O&G ,  OB-GYN  and  OB/GYN [ a ] ) is the  medical specialty  that encompasses the two subspecialties of  obstetrics  (covering  pregnancy ,  childbirth , and the  postpartum period ) and  gynaecology  (covering the health of the  female reproductive system   –  vagina ,  uterus ,  ovaries , and  breasts ). The specialization is an important part of care for  women's health .


Postgraduate training programs for both fields are usually combined, preparing the practising obstetrician-gynecologist to be adept both at the care of female reproductive organs' health and at the management of pregnancy, although many doctors go on to develop subspecialty interests in one field or the other.


According to the  American Board of Obstetrics and Gynecology  (ABOG), which is responsible for issuing OB-GYN certifications in the United States, the first step to OB-GYN certification is completing medical school to receive an MD or DO degree. [ 2 ]  From there doctors must complete a four-year OB-GYN residency program approved by the  Accreditation Council for Graduate Medical Education  (ACGME). [ 2 ] [ 3 ]  For the 2021  Electronic Residency Application Service  (ERAS) match, there were 277 OB-GYN residency programs accepting applicants. [ 4 ]