The  reproductive-cell cycle theory  posits that the  hormones  that regulate reproduction act in an antagonistic pleiotrophic manner to control aging via cell cycle signaling; promoting growth and development early in life in order to achieve reproduction, but later in life, in a futile attempt to maintain reproduction, become dysregulated and drive senescence. [ 1 ]  Rather than seeing  aging  as a loss of functionality as we get older, this theory defines aging as any change in an organism over time, as evidenced by the fact that if all chemical reactions in the body were stopped, no change, and thus no aging, would occur.  Since the most important change in an organism through time is the chemical reactions that result in a single cell developing into a multicellular organism, whatever controls these chemical reactions that regulate cell growth, development, and death, is believed to control aging. The theory argues that these cellular changes are directed by reproductive hormones of the hypothalamic-pituitary-gonadal axis ( HPG axis ).  Receptors for reproductive hormones (such as estrogens, progestogens, androgens and gonadotropins) have been found to be present in all tissues of the body.  Thus, HPG axis hormones normally promote growth and development of the organism early in life in order to achieve reproduction.  Hormones levels then begin to change in men around age 30 and more abruptly in women when they reach  menopause , around age 50.  When the HPG axis becomes unbalanced, cellular growth and development is dysregulated, and cell death and dysfunction can occur, both of which can initiate  senescence , the accumulated damage to cells, tissues, and organs that occurs with the passage of time and that is associated with functional loss during aging.


Evidence supporting this theory comes from disease studies showing that women who reach menopause later have less  heart disease  and  stroke , less  dementia , and less  osteoporosis , supporting the theory that the longer the HPG axis is in balance, the less likely one is to develop age-related diseases.  Conversely, early surgical menopause has been demonstrated to increase the incidence of these diseases.  However, the most compelling supportive evidence is from studies of  Hormone Replacement Therapy  (HRT).  Research with women and men undertaking HRT has shown that taking sex hormones that are biologically identical to human hormones delays the onset, decreases the incidence of, and can reverse the course of age related illnesses such as heart disease,  Alzheimer's disease , osteoporosis, and some types of  cancer .  However, only biological hormones appear to have these effects.  The use of non-human or synthetic hormones has been shown to increase the risk of certain of these diseases.  Compellingly, 18 studies have demonstrated an increase in longevity for those women taking HRT.


Further studies in support of the theory have shown that suppressing the HPG axis, such as when organisms experience either  caloric restriction , cold, or exercise stress, increases lifespan.  This is thought to be an evolutionary conserved mechanism that allows organisms to suppress HPG axis signaling and reproduction, thereby conserving reproductive resources ( germ cells ) for a later time when the environment is better suited to raising offspring.  By having the same hormones regulate both reproduction and aging, an animal is able to modulate its  fertility  and its rate of aging based on environmental conditions. [ 1 ]


Recent  parabiosis  studies prove many of the tenets of the Reproductive Cell-Cycle Theory of Aging. In these experiments, where a young mouse is coupled surgically with an aged mouse, circulating factors from the young mouse rejuvenates the tissues of the old mice.  In particular, these studies indicate the importance of circulating factors in regulating the maintenance of neuronal (Villeda et al., 2011), vascular (Katsimpardi et al., 2014), muscular and liver (Conboy et al., 2005; Sinha et al., 2014) structure and function.


Sexual differentiation in humans  is the process of development of  sex differences in humans . It is defined as the development of  phenotypic  structures consequent to the action of hormones produced following gonadal determination. [ 1 ]   Sexual differentiation  includes development of different genitalia and the internal genital tracts and body hair plays a role in sex identification. [ 2 ]


The development of sexual differences begins with the  XY sex-determination system  that is present in humans, and complex mechanisms are responsible for the development of the phenotypic differences between  male  and  female   humans  from an undifferentiated  zygote . [ 3 ]  Females typically have two  X chromosomes , and males typically have a  Y chromosome  and an X chromosome. At an early stage in  embryonic  development, both sexes possess equivalent internal structures. These are the  mesonephric ducts  and  paramesonephric ducts . The presence of the  SRY gene  on the Y chromosome causes the development of the testes in males, and the subsequent release of hormones which cause the  paramesonephric ducts  to regress. In females, the mesonephric ducts regress.


Disorders of sexual development (DSD), encompassing conditions characterized by  the appearance of undeveloped genitals that may be ambiguous, or look like those typical for the opposite sex, sometimes known as  intersex , can be a result of genetic and hormonal factors. [ 4 ]


Most  mammals , including humans, have an  XY sex-determination system : the  Y chromosome  carries factors responsible for triggering male development. In the absence of a Y chromosome, the fetus will undergo female development. This is because of the presence of the sex-determining region of the Y chromosome, also known as the  SRY  gene. [ 5 ]  Thus, male mammals typically have an X and a Y chromosome (XY), while female mammals typically have two  X chromosomes  (XX).


Chromosomal sex is determined at the time of  fertilization ; a  chromosome  from the  sperm  cell, either X or Y, fuses with the X chromosome in the egg cell.  Gonadal sex  refers to the gonads, that is the testicles or ovaries, depending on which genes are expressed.  Phenotypic sex  refers to the structures of the external and internal genitalia. [ 6 ]


Six weeks elapse after fertilization before the first signs of sex differentiation can be observed in human embryos. [ 5 ]  The embryo and subsequent early fetus appear to be sexually indifferent, looking neither like a male or a female. Over the next several weeks, hormones are produced that cause undifferentiated tissue to transform into either male or female reproductive organs. This process is called sexual differentiation. The precursor of the internal female sex organs is called the  Müllerian system .


Differentiation between the sexes of the sex organs occurs throughout embryological, fetal and later life. In both males and females, the sex organs consist of two structures: the internal genitalia and the external genitalia. In males, the gonads are the  testicles  and in females, they are the  ovaries . These are the organs that produce  gametes  (egg and sperm), the reproductive cells that will eventually meet to form the fertilized egg ( zygote ).


As the zygote divides, it first becomes the  embryo  (which means 'growing within'), typically between zero and eight weeks, then from the eighth week until birth, it is considered the fetus (which means 'unborn offspring'). The internal genitalia are all the accessory glands and ducts that connect the gonads to the outside environment. The external genitalia consist of all the external reproductive structures. The sex of an early embryo cannot be determined because the reproductive structures do not differentiate until the seventh week. Prior to this, the child is considered bipotential because it cannot be identified as male or female.


The internal genitalia consist of two accessory ducts:  mesonephric ducts  (male) and  paramesonephric ducts  (female). The mesonephric system is the precursor to the male genitalia and the paramesonephric to the female reproductive system. [ 8 ]  As development proceeds, one of the pairs of ducts develops while the other regresses. This depends on the presence or absence of the sex determining region of the Y chromosome, also known as the SRY  gene . [ 5 ]  In the presence of a functional SRY gene, the bipotential gonads develop into testes.  Gonads  are histologically distinguishable by 6–8 weeks of gestation.


Subsequent development of one set and degeneration of the other depends on the presence or absence of two testicular hormones:  testosterone  and  anti-Müllerian hormone (AMH) . Disruption of typical development may result in the development of both, or neither, duct system, which may produce morphologically  intersex  individuals.


Males:  The SRY gene when transcribed and processed produces SRY protein that binds to DNA and directs the development of the gonad into testes. Male development can only occur when the fetal testis secretes key hormones at a critical period in early gestation. The testes begin to secrete three hormones that influence the male internal and external genitalia: they secrete anti-Müllerian hormone (AMH),  testosterone , and  dihydrotestosterone  (DHT). Anti-Müllerian hormone causes the paramesonephric ducts to regress. Testosterone converts the mesonephric ducts into male accessory structures, including the  epididymides ,  vasa deferentia , and  seminal vesicles . Testosterone will also control the descending of the testes from the abdomen. [ 1 ]  Many other genes found on other  autosomes , including  WT1 ,  SOX9  and  SF1  also play a role in gonadal development. [ 9 ]


Females:  Without testosterone and AMH, the mesonephric ducts degenerate and disappear. The paramesonephric ducts develop into the  uterus ,  fallopian tubes , and upper  vagina  (the lower vagina develops from the urogenital sinus). [ 9 ]  There still remains a broad lack of information about the genetic controls of female development, and much remains unknown about the female embryonic process. [ 10 ]


By 7 weeks, a fetus has a  genital tubercle ,  urogenital sinus ,  urogenital folds  and  labioscrotal swellings . In females, without excess androgens, these become the  vulva  ( clitoris ,  vestibule ,  labia minora  and  labia majora  respectively). Males become externally distinct between 8 and 12 weeks, as androgens enlarge the genital tubercle and cause the urogenital groove and sinus to fuse in the midline, producing an unambiguous  penis  with a phallic urethra, and the labioscrotal swellings become a thinned, rugate  scrotum  where the testicles are situated. Dihydrotestosterone will differentiate the remaining male characteristics of the external genitalia. [ 1 ]


A sufficient amount of any androgen can cause external  masculinization . The most potent is  dihydrotestosterone  (DHT), generated from testosterone in skin and genital tissue by the action of 5α-reductase. A male fetus may be incompletely masculinized if this enzyme is  deficient . In some  diseases  and circumstances, other androgens may be present in high enough concentrations to cause partial or (rarely) complete masculinization of the external genitalia of a genetically female fetus. The testes begin to secrete three hormones that influence the male internal and external genitalia. They secrete anti-Müllerian hormone, testosterone, and Dihydrotestosterone. Anti-Müllerian hormone (AMH) causes the paramesonephric ducts to regress. Testosterone, which is secreted and converts the mesonephric ducts into male accessory structures, such as epididymis, vas deferens and seminal vesicle. Testosterone will also control the descending of the testes from the abdomen into the scrotum. Dihydrotestosterone, also known as (DHT) will differentiate the remaining male characteristics of the external genitalia. [ 11 ]


Further sex differentiation of the external genitalia occurs at  puberty , when androgen levels again become disparate. Male levels of testosterone directly induce growth of the penis, and indirectly (via DHT) the  prostate .


Alfred Jost  observed that while testosterone was required for mesonephric duct development, the regression of the  paramesonephric duct  was due to another substance. This was later determined to be paramesonephric inhibiting substance (MIS), a 140 kD dimeric glycoprotein that is produced by  Sertoli cells . MIS blocks the development of  paramesonephric ducts , promoting their regression. [ 12 ]


Visible differentiation occurs at  puberty , when  estradiol  and other hormones cause  breasts  to develop in typical females.


Human adults and children show many psychological and behavioral sex differences. Some (e.g. dress) are learned and cultural. Others are demonstrable across cultures and have both biological and learned determinants. For example, some studies claim girls are, on average, more verbally fluent than boys, but boys are, on average, better at spatial calculation. [ 13 ] [ 14 ]  Some have observed that this may be due to two different patterns in parental communication with infants, noting that parents are more likely to talk to girls and more likely to engage in physical play with boys. [ 10 ]


The following are some of the variations associated with atypical determination and differentiation process: [ 15 ]


Sexual intercourse  (also  coitus  or  copulation ) is a  sexual activity  typically involving the insertion and  thrusting  of the male  penis  inside the female  vagina  for  sexual pleasure ,   reproduction , or both. [ 1 ]  This is also known as  vaginal intercourse  or  vaginal sex . [ 2 ] [ 3 ]  Sexual penetration has been known by humans since the dawn of time, and has been an  instinctive  form of  sexual behaviour  and  psychology  among humans. Other forms of  penetrative  sexual intercourse include  anal sex  (penetration of the  anus  by the penis),  oral sex  (penetration of the mouth by the penis or oral penetration of the female  genitalia ),  fingering  (sexual penetration by the fingers) and penetration by use of a  dildo  (especially a  strap-on dildo ), and  vibrators . [ 4 ] [ 5 ]  These activities involve  physical intimacy  between two or more people and are usually used among humans solely for physical or  emotional  pleasure. They can contribute to  human bonding . [ 4 ] [ 6 ]


There are different views on what constitutes sexual intercourse or other sexual activity, which can impact on views of  sexual health . [ 7 ]  Although  sexual intercourse , particularly the term  coitus,  generally denotes penile–vaginal penetration and the possibility of creating  offspring , [ 1 ]  it also commonly denotes penetrative oral sex and penile–anal sex, especially the latter. [ 8 ]  It usually encompasses sexual penetration, while  non-penetrative sex  has been labeled  outercourse , [ 9 ]  but non-penetrative sex may also be considered sexual intercourse. [ 4 ] [ 10 ]   Sex , often a shorthand for  sexual intercourse , can mean any form of sexual activity. [ 7 ]  Because people can be at risk of contracting  sexually transmitted infections  during these activities,  safer sex  practices are recommended by health professionals to reduce transmission risk. [ 11 ] [ 12 ]


Various jurisdictions place restrictions on certain sexual acts, such as  adultery ,  incest , sexual activity with  minors ,  prostitution ,  rape ,  zoophilia ,  sodomy ,  premarital sex  and  extramarital sex .  Religious  beliefs also play a role in personal decisions about sexual intercourse or other sexual activity, such as decisions about  virginity , [ 13 ] [ 14 ]  or legal and public policy matters.  Religious views on sexuality  vary significantly between different religions and sects of the same religion, though there are common themes, such as prohibition of adultery.


Reproductive sexual intercourse between non-human animals is more often called  copulation , and  sperm  may be introduced into the female's reproductive tract in non-vaginal ways among the animals, such as by  cloacal  copulation. For most non-human  mammals ,  mating  and copulation occur at the point of  estrus  (the most fertile period of time in the female's reproductive cycle), which increases the chances of  successful impregnation . [ 15 ] [ 16 ]  However,  bonobos ,  dolphins  and  chimpanzees  are known to engage in sexual intercourse regardless of whether the female is in estrus, and to engage in  sex acts with same-sex partners . [ 17 ]  Like humans engaging in sexual activity primarily for pleasure, this behavior in these animals is also presumed to be for pleasure, and a contributing factor to strengthening their social bonds. [ 18 ]


Sexual intercourse  may be called  coitus ,  copulation ,  coition , or  intercourse .  Coitus  is derived from the  Latin  word  coitio  or  coire , meaning "a coming together or joining together" or "to go together", and is known under different ancient Latin names for a variety of sexual activities, but usually denotes penile–vaginal penetration. [ 19 ]  This is often called  vaginal intercourse  or  vaginal sex. [ 2 ] [ 20 ]   Vaginal sex,  and less often  vaginal intercourse , may also denote any vaginal sexual activity, particularly if  penetrative , including  sexual activity between lesbian couples . [ 21 ] [ 22 ]   Copulation , by contrast, more often denotes the  mating  process, especially for non-human animals; it can mean a variety of sexual activities between opposite-sex or  same-sex pairings , [ 23 ]  but generally means the  sexually reproductive  act of transferring  sperm  from a male to a female or sexual procreation between a man and a woman. [ 23 ] [ 24 ] [ 25 ]


Although  sex  and  having sex  also most commonly denote penile–vaginal intercourse, [ 26 ]   sex  can be significantly broad in its meaning and may cover any penetrative or  non-penetrative  sexual activity between two or more people. [ 7 ]  The  World Health Organization  (WHO) states that non-English languages and cultures use different words for sexual activity, "with slightly different meanings". [ 7 ]  Various  vulgarisms ,  slang , and  euphemisms  are used for sexual intercourse or other sexual activity, such as  fuck ,  screw ,  shag , and the phrase "sleep together". [ 27 ] [ 28 ] [ 29 ]  The laws of some countries use the euphemism,  carnal knowledge . Penetration of the vagina by the  erect  penis is additionally known as  intromission , or by the Latin name  immissio   penis  (Latin for "insertion of the penis"). [ 30 ]  The age of first sexual intercourse is called  sexarche . [ 31 ] [ 32 ]


Vaginal, anal and oral sex are recognized as sexual intercourse more often than other sexual behaviors. [ 33 ]  Sexual activity that does not involve penile-vaginal sex or other sexual penetration might be used to retain virginity (sometimes called  technical virginity ) or labeled  outercourse . [ 34 ]  One reason virginity loss is often based on penile–vaginal intercourse is because heterosexual couples may engage in anal or oral sex as a way of being sexually active while maintaining that they are virgins since they have not engaged in the reproductive act of coitus. [ 35 ]  Some  gay men  consider  frot  or oral sex as a way of maintaining their virginities, with penile-anal penetration used as sexual intercourse and for virginity loss, while other gay men may consider frot or oral sex as their main forms of sexual activity. [ 13 ] [ 36 ] [ 37 ]  Lesbians may categorize oral sex or  fingering  as sexual intercourse and subsequently an act of virginity loss, [ 13 ] [ 38 ]  or  tribadism  as a primary form of sexual activity. [ 39 ] [ 40 ]


Researchers commonly use  sexual intercourse  to denote penile–vaginal intercourse while using specific words, such as  anal sex  or  oral sex , for other sexual behaviors. [ 41 ]  Scholars  Richard M. Lerner  and  Laurence Steinberg  state that researchers also "rarely disclose" how they conceptualize sex "or even whether they resolved potential discrepancies" in conceptualizations of sex. [ 38 ]  Lerner and Steinberg attribute researchers' focus on penile–vaginal sex to "the larger culture's preoccupation with this form of sexual activity", and have expressed concern that the "widespread, unquestioned equation of penile–vaginal intercourse with sex reflects a failure to examine systematically 'whether the respondent's understanding of the question [about sexual activity] matches what the researcher had in mind'". [ 38 ]  This focus can also relegate other forms of mutual sexual activity to  foreplay  or contribute to them not being regarded as "real sex", and limits the meaning of  rape . [ 42 ] [ 43 ]  It may also be that conceptually conflating sexual activity with vaginal intercourse and sexual function hinders and limits information about sexual behavior that  non-heterosexual  people may be engaging in, or information about heterosexuals who may be engaging in non–vaginal sexual activity. [ 42 ]


Studies regarding the meaning of sexual intercourse sometimes come into conflict. While most consider penile–vaginal intercourse to be sex, whether anal or oral intercourse are considered sex is more debatable, with oral sex ranking lowest. [ 44 ] [ 45 ]  The  Centers for Disease Control and Prevention  (CDC) stated that "although there are only limited national data about how often adolescents engage in oral sex, some data suggest that many adolescents who engage in oral sex do not consider it to be 'sex'; therefore they may use oral sex as an option to experience sex while still, in their minds, remaining abstinent". [ 46 ]  Upton et al. stated, "It is possible that individuals who engage in oral sex, but do not consider it as 'sex', may not associate the acts with the potential health risks they can bring." [ 44 ]  In other cases,  condom  use is a factor, with some men stating that sexual activity involving the protection of a condom is not "real sex" or "the real thing". [ 47 ] [ 48 ]  This view is common among men in Africa, [ 47 ] [ 48 ]  where sexual activity involving the protection of a condom is often associated with  emasculation  because condoms prevent direct penile–to–skin genital contact. [ 47 ]


Sexual intercourse or other sexual activity can encompass various  sexually stimulating  factors ( physiological stimulation  or  psychological stimulation ), including different  sex positions  (such as the  missionary position , the most common human sex position [ 49 ] ) or the use of  sex toys . [ 50 ] [ 51 ]   Foreplay  may precede some sexual activities, often leading to  sexual arousal  of the partners and resulting in the erection of the  penis  or  natural lubrication  of the  vagina . [ 52 ]  It is also common for people to be as sexually satisfied by being kissed, touched  erotically , or held as they are during sexual intercourse. [ 53 ]


Non- primate  females copulate only when in  estrus , [ 54 ]  but sexual intercourse is possible at any time of the  menstrual cycle  for women. [ 55 ] [ 56 ]   Sex pheromones  facilitate copulatory reflexes in various organisms, but,  in humans , the detection of pheromones is impaired and they have only residual effects. [ 57 ]  Non-primate females put themselves in the crucial  lordosis position  and remain motionless, but these motor copulatory reflexes are no longer functional in women. [ 54 ]


During coitus, the partners orient their hips to allow the penis to move back and forth in the vagina to cause friction, typically without fully removing the penis. In this way, they stimulate themselves and each other, often continuing until orgasm in either or both partners is achieved. [ 10 ] [ 59 ]


For human females, stimulation of the  clitoris  plays a significant role in sexual activity; 70–80% of women require direct clitoral stimulation to achieve orgasm, [ 60 ] [ 61 ] [ 62 ]  though indirect clitoral stimulation (for example, via vaginal intercourse) may also be sufficient (see  orgasm in females ). [ 63 ] [ 64 ]  Because of this, some couples may engage in the  woman on top position  or the  coital alignment technique , a technique combining the "riding high" variation of the missionary position with pressure-counterpressure movements performed by each partner in rhythm with sexual penetration, to maximize clitoral stimulation. [ 58 ] [ 65 ]


Anal sex involves stimulation of the  anus , anal cavity, sphincter valve or  rectum ; it most commonly means the insertion of a man's penis into another person's rectum, but may also mean the use of sex toys or fingers to penetrate the anus, or oral sex on the anus ( anilingus ), or  pegging . [ 66 ]


Oral sex consists of all the sexual activities that involve the use of the mouth and throat to stimulate  genitalia  or anus. It is sometimes performed to the exclusion of all other forms of sexual activity, and may include the ingestion or absorption of semen (during  fellatio ) or vaginal fluids (during  cunnilingus ). [ 50 ] [ 67 ]


Fingering involves the digital manipulation of the clitoris, rest of the  vulva , vagina or anus for the purpose of sexual arousal and sexual stimulation; it may constitute the entire sexual encounter or it may be part of mutual masturbation, foreplay or other sexual activities. [ 22 ] [ 68 ] [ 69 ]


Natural human reproduction involves penile–vaginal penetration, [ 71 ]  during which  semen , containing male gametes known as  sperm  cells or spermatozoa, is  ejaculated  through the penis into the vagina. The sperm passes through the  vaginal vault ,  cervix  and into the  uterus , and then into the  fallopian tubes . Millions of sperm are ejaculated to increase the chances of  fertilization  (see  sperm competition ), but only one is sufficient to fertilize an egg or  ovum . When a fertile ovum from the female is present in the fallopian tubes, the male gamete fertilizes the ovum, forming a new  embryo .  Pregnancy  begins after the fertilized ovum is implanted in the lining of the uterus (the  endometrium ). [ 71 ] [ 72 ]


Pregnancy rates for sexual intercourse  are highest during the  menstrual cycle  time from some five days before until approximately one day after ovulation (this is sometimes called the  fertile window ). [ 73 ]  For optimal pregnancy chance, there are recommendations of  vaginal intercourse  every one or two days, [ 74 ]  or every two or three days. [ 75 ]  Some people who are trying to conceive may choose to time vaginal intercourse with the fertile window, a practice that is sometimes called 'timed intercourse'. [ 73 ]  Timed intercourse using urine tests that predict ovulation may help improve the rate of pregnancy and live births for some couples trying to conceive such as those who have been trying for less than 12 months and who are under 40 years old; however, it is not clear from medical evidence if timed intercourse improves the rate of ultrasound-confirmed pregnancies and it is also not clear if timed intercourse has an effect on a person's level of stress or their quality of life. [ 73 ]  Studies have shown no significant difference between different  sex positions  and pregnancy rate, as long as it results in  ejaculation  into the vagina. [ 76 ]


When a  sperm donor  has sexual intercourse with a woman who is not his partner and for the sole purpose of impregnating the woman, this may be known as natural  insemination , as opposed to  artificial insemination . Artificial insemination is a form of  assisted reproductive technology , which are methods used to achieve pregnancy by artificial or partially artificial means. [ 77 ]  For artificial insemination,  sperm donors  may donate their sperm through a  sperm bank , and the insemination is performed with the express intention of attempting to impregnate the female; to this extent, its purpose is the medical equivalent of sexual intercourse. [ 78 ] [ 79 ]   Intracervical insemination (ICI) , which involves the deposit of (usually) raw semen in the vagina of a woman, is in effect a substitute for intercourse and is often contrasted with 'normal intercourse' in this context. Reproductive methods also extend to gay and lesbian couples. For gay male pairings, there is the option of  surrogate  pregnancy; for lesbian couples, there is donor insemination in addition to choosing surrogate pregnancy. [ 80 ] [ 81 ]  Some women use artificial insemination to become  single mothers by choice . [ 82 ]


There are a variety of  safe sex  methods that are practiced by heterosexual and same-sex couples, including non-penetrative sex acts, [ 12 ] [ 83 ]  and heterosexual couples may use oral or anal sex (or both) as a means of birth control. [ 84 ] [ 85 ]  However, pregnancy can still occur with anal sex or other forms of sexual activity if the penis is near the vagina (such as during  intercrural sex  or other  genital-genital rubbing ) and its sperm is deposited near the vagina's entrance and travels along the vagina's lubricating fluids; the risk of pregnancy can also occur without the penis being near the vagina because sperm may be transported to the vaginal opening by the vagina coming in contact with fingers or other non-genital body parts that have come in contact with semen. [ 86 ] [ 87 ]


Safe sex is a relevant  harm reduction  philosophy [ 88 ]  and  condoms  are used as a form of safe sex and contraception. Condoms are widely recommended for the prevention of  sexually transmitted infections  (STIs). [ 88 ]  According to reports by the  National Institutes of Health  (NIH) and  World Health Organization  (WHO), correct and consistent use of latex condoms reduces the risk of  HIV/AIDS  transmission by approximately 85–99% relative to risk when unprotected. [ 89 ] [ 90 ]  Condoms are rarely used for oral sex and there is significantly less research on behaviors with regard to condom use for anal and oral sex. [ 91 ]  The most effective way to avoid sexually transmitted infections is to  abstain  from sexual intercourse, especially vaginal, anal, and oral sexual intercourse. [ 88 ]


Decisions and options concerning birth control can be affected by cultural reasons, such as religion,  gender roles  or  folklore . [ 92 ]  In the predominantly  Catholic  countries Ireland, Italy, and the Philippines,  fertility awareness  and the  rhythm method  are emphasized while disapproval is expressed with regard to other contraceptive methods. [ 11 ]  Worldwide,  sterilization  is a more common birth control method, [ 11 ]  and use of the  intrauterine device  (IUD) is the most common and effective way of reversible contraception. [ 11 ] [ 93 ]  Conception and contraception are additionally a life-and-death situation in  developing countries , where one in three women give birth before age 20; however, 90% of  unsafe abortions  in these countries could be prevented by effective contraception use. [ 11 ]


The  National Survey of Sexual Health and Behavior  (NSSHB) indicated in 2010 that "1 of 4 acts of vaginal intercourse are condom-protected in the U.S. (1 in 3 among singles)," that "condom use is higher among black and Hispanic Americans than among white Americans and those from other racial groups," and that "adults using a condom for intercourse were just as likely to rate the sexual extent positively in terms of arousal, pleasure and orgasm than when having intercourse without one". [ 94 ]


Penile–vaginal penetration is the most common form of sexual intercourse. [ 2 ] [ 20 ]  Studies indicate that most heterosexual couples engage in vaginal intercourse nearly every sexual encounter. [ 20 ]  The National Survey of Sexual Health and Behavior (NSSHB) reported in 2010 that vaginal intercourse is "the most prevalent sexual behavior among men and women of all ages and ethnicities". [ 20 ]  Clint E. Bruess et al. stated that it "is the most frequently studied behavior" and is "often the focus of sexuality education programming for youth." [ 95 ]  Weiten et al. said that it "is the most widely endorsed and practiced sexual act in our society." [ 40 ]


Regarding oral or anal intercourse, the CDC stated in 2009, "Studies indicate that oral sex is commonly practiced by sexually active male-female and same-gender couples of various ages, including adolescents." [ 46 ]  Oral sex is significantly more common than anal sex. [ 40 ] [ 45 ]  The 2010 NSSHB study reported that vaginal intercourse was practiced more than insertive anal intercourse among men, but that 13% to 15% of men aged 25 to 49 practiced insertive anal intercourse. Receptive anal intercourse was infrequent among men, with approximately 7% of men aged 14 to 94 years old having said that they were a receptive partner during anal intercourse. The study said that fewer women reported engaging in anal sex than other partnered sexual behaviors. It was estimated that 10% to 14% of women aged 18 to 39 years old practiced anal sex in the past 90 days, and that most of the women who engage in anal sex said they practiced it once a month or a few times a year. [ 20 ]


The prevalence of sexual intercourse has been compared cross-culturally. In 2003, Michael Bozon of the French  Institut national d'études démographiques  conducted a cross-cultural study titled "At what age do women and men have their first sexual intercourse?" In the first group of the contemporary cultures he studied, which included  sub-Saharan Africa  (listing  Mali ,  Senegal  and  Ethiopia ), the data indicated that the age of men at sexual initiation in these societies is at later ages than that of women, but is often extra-marital; the study considered the  Indian subcontinent  to also fall into this group, though data was only available from  Nepal . [ 96 ] [ 97 ]  In the second group, the data indicated families encouraged daughters to delay marriage, and to abstain from sexual activity before that time. However, sons are encouraged to gain experience with older women or prostitutes before marriage. Age of men at sexual initiation in these societies is at lower ages than that of women; this group includes  south European  and Latin cultures (Portugal, Greece and Romania are noted) and such from  Latin America  (Brazil,  Chile , and the  Dominican Republic ). The study considered many Asian societies to also fall into this group, although matching data was only available from  Thailand . [ 96 ] [ 97 ]  In the third group, age of men and women at sexual initiation was more closely matched; there were two sub-groups, however. In non-Latin, Catholic countries (Poland and  Lithuania  are mentioned), age at sexual initiation was higher, suggesting later marriage and reciprocal valuing of male and female virginity. The same pattern of late marriage and reciprocal valuing of virginity was reflected in  Singapore  and  Sri Lanka . The study considered China and Vietnam to also fall into this group, though data were not available. [ 96 ] [ 97 ]  In northern and eastern European countries, age at sexual initiation was lower, with both men and women involved in sexual intercourse before any union formation; the study listed Switzerland, Germany and the Czech Republic as members of this group. [ 96 ] [ 97 ]


Concerning United States data, tabulations by the  National Center for Health Statistics  report that the age of first sexual intercourse was 17.1 years for both males and females in 2010. [ 98 ]  The CDC stated that 45.5 percent of girls and 45.7 percent of boys had engaged in sexual activity by 19 in 2002; in 2011, reporting their research from 2006 to 2010, they stated that 43% of American unmarried teenage girls and 42% of American unmarried teenage boys have ever engaged in sexual intercourse. [ 99 ]  The CDC also reports that American girls will most likely lose their virginity to a boy who is 1 to 3 years older than they are. [ 99 ]  Between 1988 and 2002, the percentage of people in the U.S. who had sexual intercourse between the ages of 15 and 19 fell from 60 to 46 percent for never-married males, and from 51 to 46 percent for never-married females. [ 100 ]


In humans, sexual intercourse and sexual activity in general have been reported as having health benefits as varied as increased  immunity  by increasing the body's production of  antibodies  and subsequent lower  blood pressure , [ 101 ] [ 102 ]  and decreased risk of  prostate cancer . [ 101 ]  Sexual intimacy and orgasms increase levels of the hormone  oxytocin  (also known as "the love hormone"), which can help people bond and build trust. [ 102 ] [ 103 ]  Oxytocin is believed to have a more significant impact on women than on men, which may be why women associate sexual attraction or sexual activity with romance and love more than men do. [ 6 ]  A long-term study of 3,500 people between ages 18 and 102 by clinical  neuropsychologist  David Weeks indicated that, based on impartial ratings of the subjects' photographs, sex on a regular basis is associated with people looking significantly chronologically younger. However this does not imply causality. [ 104 ]


Vaginal intercourse for the first time increases vaginal immune activity. [ 105 ]


Sexually transmitted infections  (STIs) are  bacteria ,  viruses  or  parasites  that are  spread  by sexual contact, especially vaginal, anal, or oral intercourse, or  unprotected sex . [ 106 ] [ 107 ]  Oral sex is less risky than vaginal or anal intercourse. [ 108 ]  Many times, STIs initially do not cause symptoms, increasing the risk of unknowingly passing the infection on to a sex partner or others. [ 109 ] [ 110 ]


There are 19 million new cases of sexually transmitted infections every year in the U.S., [ 111 ]  and, in 2005, the World Health Organization (WHO) estimated that 448 million people aged 15–49 were infected per year with curable STIs (such as  syphilis ,  gonorrhea  and  chlamydia ). [ 112 ]  Some STIs can cause a  genital ulcer ; even if they do not, they increase the risk of both acquiring and passing on HIV up to ten-fold. [ 112 ]   Hepatitis B  can also be transmitted through sexual contact. [ 113 ]  Globally, there are about 257 million chronic carriers of hepatitis B. [ 114 ]  HIV is one of the world's leading infectious killers; in 2010, approximately 30 million people were estimated to have died because of it since the beginning of the epidemic. Of the 2.7 million new  HIV infections  estimated to occur worldwide in 2010, 1.9 million (70%) were in  Africa . The World Health Organization also stated that the "estimated 1.2 million Africans who died of HIV-related illnesses in 2010 comprised 69% of the global total of 1.8 million deaths attributable to the epidemic." [ 115 ]  It is  diagnosed by blood tests , and while no cure has been found, it can be controlled by management  through antiretroviral drugs for the disease , and patients can enjoy healthy and productive lives. [ 116 ]


In cases where infection is suspected, early medical intervention is highly beneficial in all cases. The CDC stated "the risk of HIV transmission from an infected partner through oral sex is much less than the risk of HIV transmission from anal or vaginal sex," but that "measuring the exact risk of HIV transmission as a result of oral sex is very difficult" and that this is "because most sexually active individuals practice oral sex in addition to other forms of sex, such as vaginal or anal sex, when transmission occurs, it is difficult to determine whether it occurred as a result of oral sex or other more risky sexual activities". They added that "several co-factors may increase the risk of HIV transmission through oral sex"; this includes ulcers,  bleeding gums , genital sores, and the presence of other STIs. [ 46 ]


In 2005, the World Health Organization estimated that 123 million women become pregnant worldwide each year, and around 87 million of those pregnancies or 70.7% are unintentional. Approximately 46 million pregnancies per year reportedly end in induced  abortion . [ 117 ]  Approximately 6 million U.S. women become pregnant per year. Out of known pregnancies, two-thirds result in live births and roughly 25% in abortions; the remainder end in miscarriage. However, many more women become pregnant and miscarry without even realizing it, instead mistaking the miscarriage for an unusually heavy  menstruation . [ 118 ]  The U.S.  teenage pregnancy  rate fell by 27 percent between 1990 and 2000, from 116.3 pregnancies per 1,000 girls aged 15–19 to 84.5. This data includes live births, abortions, and fetal losses. Almost 1 million American teenage women, 10% of all women aged 15–19 and 19% of those who report having had intercourse, become pregnant each year. [ 119 ]


Sexual activity can increase the expression of a  gene transcription  factor called  ΔFosB  (delta FosB) in the  brain's reward center ; [ 120 ] [ 121 ] [ 122 ]  consequently excessively frequent engagement in sexual activity on a regular (daily) basis can lead to the overexpression of ΔFosB, inducing an addiction to sexual activity. [ 120 ] [ 121 ] [ 122 ]   Sexual addiction  or  hypersexuality  is often considered an impulse control disorder or a behavioral addiction. It has been linked to atypical levels of dopamine, a neurotransmitter. This behavior is characterized by a fixation on sexual intercourse and disinhibition. It was proposed that this 'addictive behavior' be classified in  DSM-5  as an impulsive–compulsive behavioral disorder. Addiction to sexual intercourse is thought to be genetically linked. Those having an addiction to sexual intercourse have a higher response to visual sexual cues in the brain. Those seeking  treatment  will typically see a physician for pharmacological management and therapy. [ 123 ]  One form of hypersexuality is  Kleine–Levin syndrome . It is manifested by  hypersomnia  and hypersexuality and remains relatively rare. [ 124 ]


Sexual activity can directly cause death , particularly due to  coronary circulation  complications, which is sometimes called  coital death,   coital sudden death  or  coital coronary. [ 10 ] [ 125 ] [ 126 ]  However, coital deaths are significantly rare. [ 125 ]  People, especially those who get little or no physical exercise, have a slightly increased risk of triggering a  heart attack  or  sudden cardiac death  when they engage in sexual intercourse or any vigorous physical exercise that is engaged in on a sporadic basis. [ 126 ]  Regular exercise reduces, but does not eliminate, the increased risk. [ 126 ]


Sexual intercourse, when involving a male participant, often ends when the male has ejaculated, and thus the partner might not have time to reach  orgasm . [ 127 ]  In addition,  premature ejaculation  (PE) is common, and women often require a substantially longer duration of stimulation with a sexual partner than men do before reaching an orgasm. [ 52 ] [ 128 ] [ 129 ]  Scholars, such as Weiten et al., state that "many couples are locked into the idea that orgasms should be achieved only through intercourse [penile-vaginal sex]," that "the word  foreplay  suggests that any other form of sexual stimulation is merely preparation for the 'main event'" and that "because women reach orgasm through intercourse less consistently than men," they are likelier than men to  fake an orgasm  to satisfy their sexual partners. [ 52 ]


In 1991, scholars from the Kinsey Institute stated, "The truth is that the time between penetration and ejaculation varies not only from man to man, but from one time to the next for the same man." They added that the appropriate length for sexual intercourse is the length of time it takes for both partners to be mutually satisfied, emphasizing that  Kinsey  "found that 75 percent of men ejaculated within two minutes of penetration. But he didn't ask if the men or their partners considered two minutes mutually satisfying" and "more recent research reports slightly longer times for intercourse". [ 130 ]  A 2008 survey of Canadian and American  sex therapists  stated that the average time for heterosexual intercourse (coitus) was 7 minutes and that 1 to 2 minutes was too short, 3 to 7 minutes was adequate and 7 to 13 minutes desirable, while 10 to 30 minutes was too long. [ 20 ] [ 131 ]


Anorgasmia  is regular difficulty reaching orgasm after ample sexual stimulation, causing personal distress. [ 132 ]  This is significantly more common in women than in men, [ 133 ] [ 134 ]  which has been attributed to the lack of  sex education  with regard to women's bodies, especially in  sex-negative  cultures, such as clitoral stimulation usually being key for women to orgasm. [ 134 ]  The physical structure of coitus favors penile stimulation over clitoral stimulation; the location of the clitoris then usually necessitates manual or oral stimulation in order for the woman to achieve orgasm. [ 52 ]  Approximately 25% of women report difficulties with orgasm, [ 20 ]  10% of women have never had an orgasm, [ 135 ]  and 40% or 40–50% have either complained about sexual dissatisfaction or experienced difficulty becoming sexually aroused at some point in their lives. [ 136 ]


Vaginismus  is involuntary tensing of the pelvic floor musculature, making coitus, or any form of penetration of the vagina, distressing, painful and sometimes impossible for women. It is a conditioned reflex of the pubococcygeus muscle, and is sometimes referred to as the  PC muscle.  Vaginismus can be hard to overcome because if a woman expects to experience pain during sexual intercourse, this can cause a muscle spasm, which results in painful sexual intercourse. [ 134 ] [ 137 ]  Treatment of vaginismus often includes both psychological and behavioral techniques, including the use of  vaginal dilators . [ 138 ]  Additionally, the use of  Botox  as a medical treatment for vaginismus has been tested and administered. [ 139 ]  Painful or uncomfortable sexual intercourse may also be categorized as  dyspareunia . [ 138 ]


Approximately 40% of males reportedly have some form of  erectile dysfunction  (ED) or impotence, at least occasionally. [ 140 ]  Premature ejaculation has been reported to be more common than erectile dysfunction, although some estimates suggest otherwise. [ 128 ] [ 129 ] [ 140 ]  Due to various meanings of the disorder, estimates for the prevalence of premature ejaculation vary significantly more than for erectile dysfunction. [ 128 ] [ 129 ]  For example, the  Mayo Clinic  states, "Estimates vary, but as many as 1 out of 3 men may be affected by [premature ejaculation] at some time." [ 141 ]  Further, "Masters and Johnson speculated that premature ejaculation is the most common sexual dysfunction, even though more men seek therapy for erectile difficulties" and that this is because "although an estimated 15 percent to 20 percent of men experience difficulty controlling rapid ejaculation, most do not consider it a problem requiring help, and many women have difficulty expressing their sexual needs". [ 130 ]  The  American Urological Association  (AUA) estimates that premature ejaculation could affect 21 percent of men in the United States. [ 142 ]


For those whose impotence is caused by medical conditions, prescription drugs such as  Viagra ,  Cialis , and  Levitra  are available. However, doctors caution against the unnecessary use of these drugs because they are accompanied by serious risks such as increased chance of heart attack. [ 143 ]  The  selective serotonin reuptake inhibitor  (SSRI) and antidepressant drug  dapoxetine  has been used to treat premature ejaculation. [ 144 ]  In clinical trials, those with PE who took dapoxetine experienced sexual intercourse three to four times longer before orgasm than without the drug. [ 145 ]  Another ejaculation-related disorder is  delayed ejaculation , which can be caused as an unwanted side effect of antidepressant medications such as  fluvoxamine ; however, all SSRIs have ejaculation-delaying effects, and fluvoxamine has the least ejaculation-delaying effects. [ 146 ]


Sexual intercourse often remains possible after major medical treatment of the reproductive organs and structures. This is especially true for women. Even after extensive gynecological surgical procedures (such as  hysterectomy ,  oophorectomy ,  salpingectomy ,  dilation and curettage ,  hymenotomy ,  Bartholin gland  surgery, abscess removal,  vestibulectomy ,  labia minora  reduction,  cervical conization ,  surgical  and radiological cancer treatments and chemotherapy), sexual intercourse can continue. Reconstructive surgery remains an option for women who have experienced benign and malignant conditions. [ 147 ]  Men and women who have underwent extensive surgery should consult their medical team to understand how their treatment or surgery affects sex and how long they should wait before having sexual intercourse after a surgery. [ 148 ] [ 149 ]


Obstacles that those with  disabilities  face with regard to engaging in sexual intercourse include pain,  depression , fatigue,  negative body image , stiffness, functional impairment, anxiety, reduced  libido , hormonal imbalance, and drug treatment or side effects. Sexual functioning has been regularly identified as a neglected area of the quality of life in patients with  rheumatoid arthritis . [ 150 ]  For those that must take opioids for pain control, sexual intercourse can become more difficult. [ 151 ]  Having a  stroke  can also largely impact on the ability to engage in sexual intercourse. [ 152 ]  Although disability-related pain, including as a result of  cancer , and mobility impairment can hamper sexual intercourse, in many cases, the most significant impediments to sexual intercourse for individuals with a disability are psychological. [ 153 ]  In particular, people who have a disability can find sexual intercourse daunting due to issues involving their  self-concept  as a sexual being, or a partner's discomfort or perceived discomfort. [ 153 ]  Temporary difficulties can arise with  alcohol and sex , as alcohol can initially increase interest through disinhibition but decrease capacity with greater intake; however, disinhibition can vary depending on the culture. [ 154 ] [ 155 ]


People with  mental disabilities  also are subject to challenges in participating in sexual intercourse. This can include the lack of a knowledgeable healthcare provider trained and experienced in counseling those with  intellectual disabilities  on sexual intercourse. Those with intellectual disabilities may have hesitations regarding the discussion of the topic of sex, a lack of sexual knowledge and limited opportunities for sex education. [ 156 ]  In addition there are other barriers such as a higher prevalence of sexual abuse and assault. These crimes often remain underreported. There remains a lack of "dialogue around this population's human right to consensual sexual expression, undertreatment of menstrual disorders, and legal and systemic barriers". Women with intellectual disability may lack sexual health care and sex education. They may not recognize sexual abuse. Consensual sexual intercourse is not always an option for some. Those with intellectual disability may have limited knowledge and access to contraception, screening for sexually transmitted infections and cervical cancer. [ 157 ]


Sexual intercourse may be for reproductive, relational, or recreational purposes. [ 158 ]  It often plays a strong role in  human bonding . [ 6 ]  In many societies, it is normal for couples to have sexual intercourse while using some method of birth control, sharing pleasure and strengthening their emotional bond through sexual activity even though they are deliberately avoiding pregnancy. [ 6 ]


In humans and  bonobos , the female undergoes relatively  concealed ovulation  so that male and female partners commonly do not know whether she is fertile at any given moment. One possible reason for this distinct biological feature may be formation of strong emotional bonds between sexual partners important for social interactions and, in the case of humans, long-term partnership rather than immediate sexual reproduction. [ 55 ]


Sexual dissatisfaction  due to the lack of sexual intercourse is associated with increased risk of  divorce  and relationship dissolution, especially for men. [ 159 ] [ 160 ] [ 161 ]  Some research, however, indicates that general dissatisfaction with  marriage  for men results if their wives  flirted  with, erotically kissed or became romantically or sexually involved with another man ( infidelity ), [ 159 ] [ 160 ]  and that this is especially the case for men with a lower emotional and composite marital satisfaction. [ 161 ]  Other studies report that the lack of sexual intercourse does not significantly result in divorce, though it is commonly one of the various contributors to it. [ 162 ] [ 163 ]  According to the 2010 National Survey of Sexual Health and Behavior (NSSHB), men whose most recent sexual encounter was with a relationship partner reported greater arousal, greater pleasure, fewer problems with erectile function, orgasm, and less pain during the event than men whose last sexual encounter was with a non-relationship partner. [ 164 ]


For women, there is often a complaint about the lack of their spouses' sexual spontaneity. Decreased sexual activity among these women may be the result of their perceived failure to maintain ideal  physical attractiveness  or because their sexual partners' health issues have hindered sexual intercourse. [ 165 ]  Some women express that their most satisfying sexual experiences entail being connected to someone, rather than solely basing satisfaction on orgasm. [ 127 ] [ 166 ]  With regard to divorce, women are more likely to divorce their spouses for a  one-night stand  or various infidelities if they are in less cooperative or high-conflict marriages. [ 161 ]


Research additionally indicates that non-married couples who are  cohabiting  engage in sexual intercourse more often than married couples, and are more likely to participate in sexual activity outside of their sexual relationships; this may be due to the " honeymoon " effect (the newness or novelty of sexual intercourse with the partner), since sexual intercourse is usually practiced less the longer a couple is married, with couples engaging in sexual intercourse or other sexual activity once or twice a week, or approximately six to seven times a month. [ 167 ]   Sexuality in older age  also affects the frequency of sexual intercourse, as older people generally engage in sexual intercourse less frequently than younger people do. [ 167 ]


Adolescents commonly use sexual intercourse for relational and recreational purposes, which may negatively or positively impact their lives. For example, while  teenage pregnancy  may be welcomed in some cultures, it is also commonly disparaged, and research suggests that the  earlier onset of puberty  for children puts pressure on children and teenagers to act like adults before they are emotionally or cognitively ready. [ 168 ]  Some studies have concluded that engaging in sexual intercourse leaves adolescents, especially girls, with higher levels of stress and depression, and that girls may be likelier to engage in sexual risk (such as sexual intercourse without the use of a condom), [ 169 ] [ 170 ]  but it may be that further research is needed in these areas. [ 170 ]  In some countries, such as the United States,  sex education  and  abstinence-only sex education  curricula are available to educate adolescents about sexual activity; these programs are controversial, as debate exists as to whether teaching children and adolescents about sexual intercourse or other sexual activity should only be left up to parents or other  caregivers . [ 171 ]


Some studies from the 1970s through 1990s suggested an association between  self-esteem  and sexual intercourse among adolescents, [ 172 ]  while other studies, from the 1980s and 1990s, reported that the research generally indicates little or no relationship between self-esteem and sexual activity among adolescents. [ 173 ]  By the 1990s, the evidence mostly supported the latter, [ 173 ]  and further research has supported little or no relationship between self-esteem and sexual activity among adolescents. [ 174 ] [ 175 ]  Scholar Lisa Arai stated, "The idea that early sexual activity and pregnancy is linked to low self-esteem became fashionable in the latter half of the 20th century, particularly in the US," adding that, "Yet, in a systematic review of the relationship between self-esteem and teenagers' sexual behaviours, attitudes and intentions (which analyzed findings from 38 publications) 62% of behavioral findings and 72% of the attitudinal findings exhibited no statistically significant associations (Goodson et al, 2006)." [ 175 ]  Studies that do find a link suggest that non-virgin boys have higher self-esteem than virgin boys and that girls who have low self-esteem and poor  self-image  are more prone to risk-taking behaviors, such as unprotected sex and  multiple sexual partners . [ 172 ] [ 174 ] [ 175 ]


Psychiatrist  Lynn Ponton  wrote, "All adolescents have sex lives, whether they are sexually active with others, with themselves, or seemingly not at all", and that viewing adolescent sexuality as a potentially positive experience, rather than as something inherently dangerous, may help young people develop healthier patterns and make more positive choices regarding sexual activity. [ 168 ]  Researchers state that long-term romantic relationships allow adolescents to gain the skills necessary for high-quality relationships later in life. [ 176 ]  Overall, positive romantic relationships among adolescents can result in long-term benefits. High-quality romantic relationships are associated with higher commitment in early adulthood, [ 177 ]  and are positively associated with social competence. [ 178 ] [ 179 ]


While sexual intercourse, as coitus, is the natural mode of reproduction for the human species, humans have intricate moral and ethical guidelines which regulate the practice of sexual intercourse and vary according to  religious  and governmental laws. Some governments and religions also have strict designations of what they consider appropriate and inappropriate sexual behavior, which include restrictions on the types of sex acts which are permissible. A historically prohibited or regulated sex act is anal sex. [ 180 ] [ 181 ]


Sexual intercourse with a person against their will, or without their  consent , is  rape , but may also be called  sexual assault ; it is considered a serious  crime  in most countries. [ 182 ] [ 183 ]  More than 90% of rape victims are female, 99% of rapists male, and only about 5% of rapists are strangers to the victims. [ 183 ]


Most countries have  age of consent  laws which set the minimum legal age with whom an older person may engage in sexual intercourse, usually set at 16 to 18, but ranges from 12 to 20, years of age. In some societies, an age of consent is set by non-statutory custom or tradition. [ 184 ]  Sex with a person under the age of consent, regardless of their stated consent, is often considered sexual assault or  statutory rape  depending on differences in ages of the participants. Some countries treat any sex with a person of diminished or insufficient mental capacity to give consent, regardless of age, as rape. [ 185 ]


Robert Francoeur et al. stated that "prior to the 1970s, rape definitions of sex often included only penile-vaginal sexual intercourse." [ 186 ]  Authors Pamela J. Kalbfleisch and Michael J. Cody stated that this made it so that if "sex means penile-vaginal intercourse, then rape means forced penile-vaginal intercourse, and other sexual behaviors – such as fondling a person's genitals without her or his consent, forced oral sex, and same-sex coercion – are not considered rape"; they stated that "although some other forms of forced sexual contact are included within the legal category of sodomy (e.g., anal penetration and oral-genital contact), many unwanted sexual contacts have no legal grounding as rape in some states". [ 43 ]  Ken Plumber argued that the legal meaning "of rape in most countries is unlawful sexual intercourse which means the penis must penetrate the vagina" and that "other forms of sexual violence towards women such as forced oral sex or anal intercourse, or the insertion of other objects into the vagina, constitute the 'less serious' crime of sexual assault". [ 187 ]


Over time, the meaning of rape broadened in some parts of the world to include many types of sexual penetration, including anal intercourse, fellatio, cunnilingus, and penetration of the genitals or rectum by an inanimate object. [ 186 ]  Until 2012, the  Federal Bureau of Investigation  (FBI) still considered rape a crime solely committed by men against women. In 2012, they changed the meaning from "The carnal knowledge of a female forcibly and against her will" to "The penetration, no matter how slight, of the vagina or anus with any body part or object, or oral penetration by a sex organ of another person, without the consent of the victim." The meaning does not change federal or state criminal codes or impact charging and prosecution on the federal, state or local level, but instead assures that rape will be more accurately reported nationwide. [ 188 ] [ 189 ]  In some instances, penetration is not required for the act to be categorized as rape. [ 190 ]


In most societies around the world, the concept of  incest  exists and is criminalized. James Roffee, a senior lecturer in criminology at  Monash University , [ 191 ]  addressed potential harm associated with familial sexual activity, such as resulting children born with deficiencies. However, the law is more concerned with protecting the rights of people who are potentially subjected to such abuse. This is why familial sexual relationships are criminalized, even if all parties are consensual. There are laws prohibiting all kinds of sexual activity between relatives, not necessarily penetrative sex. These laws refer to grandparents, parents, children, siblings, aunts and uncles. There are differences between states in terms of the severity of punishments and what they consider to be a relative, including biological parents, step-parents, adoptive parents and half-siblings. [ 192 ]


Another sexual matter concerning consent is  zoophilia , which is a  paraphilia  involving sexual activity between human and non-human animals, or a fixation on such practice. [ 193 ] [ 194 ] [ 195 ]  Human sexual activity with non-human animals is not outlawed in some jurisdictions, but it is illegal in others under  animal abuse  laws or laws dealing with  crimes against nature . [ 196 ]


Sexual intercourse has traditionally been considered an essential part of a marriage, with many religious customs requiring  consummation  of the marriage and citing marriage as the most appropriate union for sexual reproduction (procreation). [ 197 ]  In such cases, a failure for any reason to consummate the marriage would be considered a ground for  annulment  (which does not require a divorce process). Sexual relations between marriage partners have been a "marital right" in various societies and religions, both historically and in modern times, especially with regard to a husband's rights to his wife. [ 198 ] [ 199 ] [ 200 ]  Until the late 20th century, there was usually a  marital exemption  in  rape laws  which precluded a husband from being prosecuted under the rape law for forced sex with his wife. [ 201 ]  Author Oshisanya, 'lai Oshitokunbo stated, "As the legal status of women has changed, the concept of a married man's or woman's marital right to sexual intercourse has become less widely held." [ 202 ]


Adultery  (engaging in sexual intercourse with someone other than one's spouse) has been, and remains, a criminal offense in some jurisdictions. [ 203 ] [ 204 ]  Sexual intercourse between unmarried partners and cohabitation of an unmarried couple are also illegal in some jurisdictions. [ 205 ] [ 206 ]  Conversely, in other countries, marriage is not required, socially or legally, in order to have sexual intercourse or to procreate (for example, the majority of births are outside of marriage in countries such as Iceland, Norway, Sweden, Denmark, Bulgaria, Estonia, Slovenia, France, Belgium). [ 207 ]


With regard to  divorce laws , the refusal to engage in sexual intercourse with one's spouse may give rise to a  grounds for divorce , which may be listed under "grounds of abandonment". [ 208 ]  Concerning  no-fault divorce  jurisdictions, author James G. Dwyer stated that no-fault divorce laws "have made it much easier for a woman to exit a marital relationship, and wives have obtained greater control over their bodies while in a marriage" because of legislative and judicial changes regarding the concept of a marital exemption when a man rapes his wife. [ 198 ]


There are various legal positions regarding the meaning and legality of sexual intercourse between persons of the same sex or gender. For example, in the 2003  New Hampshire Supreme Court  case  Blanchflower v. Blanchflower , it was held that female same-sex sexual relations, and same-sex sexual practices in general, did not constitute sexual intercourse, based on a 1961 entry in  Webster's Third New International Dictionary  that categorizes sexual intercourse as coitus; and thereby an accused wife in a divorce case was found not guilty of  adultery . [ 209 ] [ 210 ]  Some countries consider same-sex sexual behavior an offense punishable by imprisonment or execution; this is the case, for example,  in Islamic countries , including  LGBT issues in Iran . [ 211 ] [ 212 ]


Opposition to  same-sex marriage  is largely based on the belief that sexual intercourse and sexual orientation should be of a heterosexual nature. [ 213 ] [ 214 ] [ 215 ]  The recognition of such marriages is a  civil rights , political, social, moral and religious issue in many nations, and the conflicts arise over whether same-sex couples should be allowed to enter into marriage, be required to use a different status (such as a  civil union , which either grant equal rights as marriage or limited rights in comparison to marriage), or not have any such rights. A related issue is whether the word  marriage  should be applied. [ 214 ] [ 215 ]


There are wide differences in religious views with regard to sexual intercourse in or outside of marriage:


In some cases, the sexual intercourse between two people is seen as contrary to religious law or doctrine. In many religious communities, including the  Catholic Church  and  Mahayana Buddhists , religious leaders are expected to refrain from sexual intercourse in order to devote their full attention, energy, and loyalty to their religious duties. [ 243 ]


In  zoology ,  copulation  often means the process in which a male introduces sperm into the female's body, especially directly into her reproductive tract. [ 15 ] [ 24 ]   Spiders  have separate male and female sexes. Before mating and copulation, the male spider spins a small web and ejaculates on it. He then stores the sperm in reservoirs on his large  pedipalps , from which he transfers sperm to the female's genitals. The females can store sperm indefinitely. [ 244 ]


Many animals that live in water use  external fertilization , whereas  internal fertilization  may have developed from a need to maintain  gametes  in a liquid medium in the  Late Ordovician  epoch. Internal fertilization with many vertebrates (such as  reptiles , some  fish , and most  birds ) occur via  cloacal  copulation (see also  hemipenis ), while  mammals  copulate vaginally, and many  basal   vertebrates  reproduce sexually with external fertilization. [ 245 ] [ 246 ]


For primitive  insects , the male deposits  spermatozoa  on the substrate, sometimes stored within a special structure;  courtship  involves inducing the female to take up the sperm package into her genital opening, but there is no actual copulation. [ 247 ] [ 248 ]  In groups that have reproduction similar to spiders, such as  dragonflies , males extrude sperm into secondary copulatory structures removed from their genital opening, which are then used to inseminate the female. In dragonflies, it is a set of modified  sternites  on the second abdominal segment. [ 249 ]  In advanced groups of insects, the male uses its  aedeagus , a structure formed from the terminal segments of the abdomen, to deposit sperm directly (though sometimes in a capsule called a  spermatophore ) into the female's reproductive tract. [ 250 ]


Bonobos, chimpanzees and dolphins are species known to engage in heterosexual behaviors even when the female is not in estrus, which is a point in her reproductive cycle suitable for successful impregnation. These species are also known to  engage in same-sex sexual behaviors . [ 17 ]  In these animals, the use of sexual intercourse has evolved beyond reproduction to apparently serve additional social functions (such as bonding). [ 18 ]


Sialyl Lewis X  (sLeX) , also known as  cluster of differentiation 15s  ( CD15s ) or  stage-specific embryonic antigen 1  ( SSEA-1 ), is a tetrasaccharide  carbohydrate  which is usually attached to O- glycans  on the surface of cells. It is known to play a vital role in cell-to-cell recognition processes. It is also the means by which an egg attracts sperm; first, to stick to it, then bond with it and eventually form a zygote.


Sialyl-Lewis X  is also one of the most important  blood group antigens  and is displayed on the terminus of glycolipids that are present on the cell surface. The sialyl-Lewis X  determinant, E- selectin  ligand carbohydrate structure, is constitutively expressed on  granulocytes  and  monocytes  and mediates inflammatory extravasation of these cells. Resting  T  and  B   lymphocytes  lack its expression and are induced to strongly express sialyl-Lewis X  upon activation. The sialyl-Lewis X  determinant is expressed preferentially on activated  T h 1 cells  but not on  T h 2 cells .


Sialyl-Lewis X  is a tetrasaccharide composed of a  sialic acid ,  fucose  and an  N -acetyllactosamine . Its systematic name is 5-acetylneuraminyl-(2-3)-galactosyl-(1-4)-(fucopyranosyl-(1-3))- N -acetylglucosamine (Neu5Acα2-3Galβ1-4[Fucα1-3]GlcNAcβ). In humans, [ 1 ] [ 2 ]  it is synthesized by four  fucosyltransferases :  FUT3 ,  FUT5 ,  FUT6  and  FUT7 . The other three enzymes of the  sialyltransferase  family,  ST3GAL3 ,  ST3GAL4 , and  ST3GAL6 , participate in the synthesis of the sialyl-Lewis X  precursor. [ 2 ]


Sialyl-Lewis X  is important in leukocyte tethering and rolling. Leukocytes move through the blood stream and then tether themselves to the endothelial wall and roll along the endothelium before potentially exiting into the tissue. Sialyl-Lewis X  is a necessary partner for the three selectins that bind the leukocyte and endothelial cells. When sialyl-Lewis X  is part of an O-glycan and attached to CD34, it can then bind to L-selectin. For the binding to L-selectin to occur, sialyl-Lewis X  must undergo sulfation. For sialyl-Lewis X  to bind to P-selectin, an O-linked glycan near the N-terminus of P-selectin glycoprotein ligand-1 (PSGL-1) is modified with sialyl-Lewis X  and, in combination with nearby tyrosine residues modified with sulfate, forms the binding contact for P-selectin. For sialyl-Lewis X  to bind to E-selectin, it can be part of either an N-linked or O-linked glycan attached to cell surface glycoproteins such as PSGL-1, CD43 or CD44. This sialyl-Lewis X -mediated binding to selectins allows circulating leukocytes to stick to and roll along endothelial cells lining blood vessels, thereby enabling the leukocytes to accumulate at a site of vascular inflammation.


Sialyl-Lewis X  allows a sperm cell to recognize and fertilize an egg cell. For fertilization to occur, human sperm must bind to the  zona pellucida  (ZP), the translucent matrix covering the human egg composed of four glycoproteins—ZP1, 2, 3, and 4—and transit through the matrix in order to fuse with the oocyte. [ 3 ]  The human ZP is coated with dense N- and O-glycans that are terminated with the sialyl-Lewis X  sequence. [ 4 ]  The hemizona assay, which assesses sperm–ZP binding by counting the number of sperm bound to hemispheres of bisected nonliving human eggs  in vitro , reveals that 0.5 mM sialyl-Lewis X  inhibits sperm–ZP binding by 63%. [ 4 ]  Furthermore, adding purified and solubilized ZP3 or ZP4 from the human oocyte dose-dependently inhibits sperm–ZP binding in the hemizona assay. [ 5 ]   Such evidence suggest that the early steps of human sperm–egg binding may be mediated by lectins for sialyl-Lewis X  present on human sperm.


Defective synthesis of the sialyl-Lewis X  antigen results in immunodeficiency ( leukocyte adhesion deficiency  type 2). Defective synthesis can be caused by the loss of fucosyltransferase, impairing the glycosylation of the glycosphingolipid. Sialyl-Lewis X  is being researched for detection and treatment of immune disorders because of its presence on leukocytes.


Sialyl-Lewis X  mediates  phagocytosis  and  chemotaxis , found in neutrophils; [ 6 ]  it is expressed by cells present in Hodgkin disease, some B-cell chronic lymphocytic leukemias, acute lymphoblastic leukemias, and most acute nonlymphocytic leukemias. CD15 is present on almost all  Reed–Sternberg cells , including their rare mononuclear variants, and, as such, can be used in  immunohistochemistry  to identify the presence of such cells in biopsies. The presence of these cells is diagnostic of  Hodgkin's lymphoma . Reed–Sternberg cells display a characteristic pattern of sialyl-Lewis X  positivity, with membranous staining combined with staining of the  Golgi apparatus . Immunohistochemical panels for the diagnosis of Hodgkin's disease typically employ CD15 along with  CD30  and  CD45 ; the latter does not stain Reed–Sternberg cells, but does stain almost all other lymphoid cells. Sialyl-Lewis X  is also present in about 50% of  adenocarcinoma  cells and can be used to distinguish such conditions from  mesothelioma , which is typically negative. [ 7 ]


Sialyl-Lewis X  plays a critical role in cancer metastasis, facilitating the extravasation of cancer cells out of the bloodstream when they are moving through the body. Its expression is related to tumor stage, recurrence, and overall patient survival. [ 8 ]  Therefore, sialyl Lewis x is being used as a target in studies to fight tumors and cancer cell growth. There is frequent overexpression of sialyl-Lewis X  on cancer cells, and it is found on both N-glycan and O-glycans. Sialyl-Lewis X  is being researched with CD markers to find new ways to create biosensors for cancer cells. It is also being used in new ways to target cancer cells specifically for cancer treatment. [ 9 ]


Sialyl-Lewis X  is being used to achieve greater rates of fertilization of eggs in women by coating the eggs with sialyl-Lewis X .


Sialyl-Lewis X  plays a key role in the inflammatory response and may be used to increase the leukocyte response to infections. Sialyl-Lewis X  is also an inflammation-associated antigen on liver cells. It is overexpressed on diseased liver cells and can be used as a way to detect liver disease in a patient.


In June 2019, before the onset of the  COVID-19 pandemic , the receptor for sulfated sialyl-Lewis X  oligosaccharide (particularly with α2,3 linkages) was found to be the preferred binding site, both in humans and in dromedary camels, for the coronavirus causing Middle East respiratory syndrome ( MERS ), the sixth coronavirus to be described. [ 10 ] [ 11 ]


The term "Lewis" in the name comes from a family of people with a red blood cell incompatibility. The studies done on these individuals' red blood cells led to the discovery of sialyl-Lewis X . Sialyl-Lewis X  is an important red blood cell antigen present on the glycolipids on the plasma membrane of the cell.


Its localization to the cell surface of cells led to its alternative nomenclature as a  cluster of differentiation . Clusters of differentiation are a naming system devised in 1982 to classify cell-surface antigens on  leukocytes  identified via  monoclonal antibodies . Sialyl-Lewis X  was assigned the name CD15.


The  Special Program of Assisted Reproduction  ( SPAR ) is a program offered to  HIV  discordant couples ( serodiscordant ) at the  Bedford Research Foundation 's clinical laboratory. The program takes advantage of ART ( assisted reproduction technology ) procedures (including " sperm washing " [ 1 ] ) to assist couples achieve a pregnancy who would otherwise risk transmitting the father's  HIV  infection to the mother and the child through intercourse.


SPAR employs extremely stringent safety standards; samples will only be submitted for "sperm washing" and  cryopreservation  that have first been screened for HIV  virus  particles and infected cells by specialized  molecular biology  tests. Only samples that have been determined to have an undetectable HIV  viral burden  will be submitted for  infertility  procedures.


Assisted reproductive technologies (ART), such as  in vitro fertilization  (IVF), treat many disorders of the female, but until recent years, treatment options for  male factor infertility  were limited, and donor  sperm  was routinely recommended to achieve a pregnancy. Advances in ART, however, have created new possibilities for men with male factor infertility, including those whose sperm counts have been decreased by  cancer treatment  and other diseases, and men with incurable, sexually transmissible virus diseases.


Infectious diseases transmissible by semen for which there is no cure include:


SPAR began in 1994 at the New England Deaconess Hospital (now  Beth Israel Deaconess Medical Center ) as a support group for couples wishing to parent when one of them had an incurable  sexually transmitted disease . The patient couples began raising money to fund the research needed to develop the methods to improve the safety of attempting pregnancy. By 1996 sufficient funds were available to begin, but a merger between the  Beth Israel Hospital  and the New England Deaconess Hospital (now  Beth Israel Deaconess Medical Center ) necessitated the creation of an independent  Massachusetts   public charity , the Assisted Reproduction Foundation (now the  Bedford Stem Cell Research Foundation  directed by Dr.  Ann Kiessling ), to continue the work. Within two years, the methods for reducing, and perhaps eliminating, the risks of infection to the mother and the child were developed and Baby Ryan [ 2 ]  was born in 1999.


The goal of SPAR was to provide semen testing by experts that would ensure improved safety of sperm that could then be shipped to infertility clinics near the couple's home. In this way, couples could be cared for in the same manner as other couples in their community. Fortunately, a few clinics were willing to help with this effort, and by 2002, seven collaborating clinics around the country were caring for couples living with  HIV  disease.


In the Spring of 2000 a ground breaking study was completed, giving significant insight to the role of semen producing organs in  HIV   anti-viral  therapy.  [ 3 ]


A  sperm granuloma  is a lump of leaked  sperm  that appears along the  vasa deferentia  or  epididymides  in  vasectomized  individuals.  While the majority of sperm granulomas are present along the vas deferens, the rest of them form at the epididymis. Sperm granulomas range in size, from one millimeter to one centimeter. They consist of a central mass of degenerating sperm surrounded by tissue containing blood vessels and immune system cells. [ 1 ]  Sperm granulomas may also have a yellow, white, or cream colored center when cut open. While some sperm granulomas can be painful, most of them are painless and asymptomatic. [ 2 ]  Sperm granulomas can appear as a result of surgery (such as a vasectomy), trauma, or an infection (such as sexually transmitted diseases). [ 3 ]  They can appear as early as four days after surgery and fully formed ones can appear as late as 208 days later. [ 4 ]


Sperm granulomas are a common complication of different types of vasectomy. In vasectomies, the vas deferens are cut and the two ends are tied to prevent sperm from passing. Sperm granuloma may then form at the point where the vas deferens were cut, due to the possibility of sperm leaking out at this site. History of trauma or inflammation of the epididymis can also lead to a sperm granuloma. [ 2 ]  Sperm granulomas are seen as the body's immune response to sperm being outside of their normal location, and are therefore seen as a protective mechanism.


Sperm granulomas are quite common after surgery, occurring in up to 40% of patients. On the contrary, sperm granulomas comprise only 2.5% of the general population. [ 5 ]  Amongst adolescents and pediatric patients, sperm granulomas are considered a rare phenomenon as this population does not undergo vasectomy often. The most common cause of sperm granuloma in pediatric and adolescent patients is often attributed to tumor obstruction, injury, or infection to the area. [ 5 ]


While sperm granuloma is considered a complication in most cases, it allows decompression of the vas deferens and epididymis at the vasectomy site. This allows for successful future reversal of vasectomy given the good quality sperm in the vas fluid. Any surgery in the genital area can lead to castration anxiety (fear of loss or damage to the genital organ.) [ 6 ]


Sperm granulomas are diagnosed using a microscope to examine tissues ( histology ) taken from the area, typically done with  fine needle aspiration  and occur within a few weeks of a vasectomy. [ 7 ]  An example of a histology based diagnosis supporting sperm granuloma would be a sperm core surrounded by inflammatory cells,  apoptotic cells , and fibrous tissue. Often, there will be empty tubes with cellular debris near the granuloma. [ 2 ]  Additionally, physicians might use  high frequency ultrasounds  to aid in properly diagnosing epididymal conditions such as sperm granulomas. [ 8 ]  Using these ultrasounds provide a better view of the anatomy of the epididymis, which could prevent misdiagnosis of conditions such as testicular tumors or supernumerary testis (the presence of more than two testes). [ 8 ]


Sperm granulomas appear as hard and firm nodules that do not exceed 1 cm in size. Sperm granulomas form in 20-50% of vasectomy procedures. [ 6 ]  An injury to the epididymal epithelium is caused by penetration of germ cells into the epididymal supportive tissue. This infiltration of germ cells allows for the pathogenesis of sperm granulomas. Moreover, the penetration of germ cells leads to inflammatory and autoimmune reactions that further increase the risk of sperm granuloma formation. [ 2 ]


Sperm granuloma can also mimic the presence of an abnormal number of testis on ultrasound. [ 9 ]


Sperm granulomas are mostly asymptomatic. [ 4 ]  However, they can cause pain and swelling of the epididymis, spermatic cord, and testis. The pain usually radiates to the groin, the junctional area between the abdominal wall and the thigh, and can imitate the feeling of kidney spasms. [ 10 ]


Sperm granuloma is a common complication of vasectomy. [ 2 ]  Vasectomies are a common, effective procedure for the sterilization of males. History of trauma or epididymitis can also lead to sperm granuloma. In vasectomies, the vas deferens are cut and the two ends are tied to prevent sperm from passing. Sperm granuloma may then grow at the point where the vas deferens were cut. [ 2 ]  This could happen two to three weeks post procedure. Sperm granuloma can also form from sperm leaking from the vas deferens into the surrounding interstitium. Leakage of sperm elicits an immune response which can lead to chronic inflammation. A histological examination can confirm a sperm granuloma by checking for inflammatory markers such as macrophages and lymphocytes surrounding the sperm core. [ 2 ]


Most sperm granulomas are asymptomatic and absorbed over time. However, in more severe cases, non-steroidal anti-inflammatory drugs (NSAIDs) such as Ibuprofen may be used.


Surgery is very rarely performed. In cases where symptoms do not resolve in a reasonable amount of time and NSAID therapy is ineffective, the provider may choose to surgically resect the area where the pain is localized. Additionally, the stumps of the vas deferens can be burned and closed off in order to reduce the pain the patient is experiencing and prevent it from happening again. [ 11 ]


When sperm granulomas are occasionally mistaken for other conditions, such as testicular tumors, a more complicated treatment approach such as an  orchiectomy  may be accidentally used. [ 12 ]


Cauterization is a vasectomy method used to seal the vas deferens by utilizing heat or electricity to burn the lumen. Using thermal (heat) cautery instead of electrocautery can help prevent granulomas and nodular thickening. [ 2 ]


Refraining from ejaculation for 1 week can potentially reduce the risk of developing a sperm granuloma. [ 2 ]


There is also evidence that sperm granuloma formation may be linked to testosterone deficiency. Testosterone supplementation may reduce the inflammation related to sperm granulomas and potentially even prevent them from occurring. [ 2 ]  However, this evidence is only supported in animal models.


There have been complications involving sperm granuloma. A pediatric case documented a 13 year old boy who was admitted to the hospital with  edema  and redness on his left  hemiscrotum . [ 13 ]  Upon a physical examination, they found the scrotum to be enlarged, soft, red and painless. Initial sonographs detected possibility of inflammation of the testis and epididymis. The patient received anti-inflammatory and antibiotic treatment, and was examined again one week after treatment. [ 13 ]  The testis were still painless and now hardened. Upon a second reexamination five days later, low perfusion to the testis was detected. This testicular necrosis led the patient into an emergency operation. Histology determined there was a ruptured sperm granuloma that led to the testicular thrombosis and necrosis. [ 13 ]  Specifically, the walls of the vas deferens contained many growths of small ducts and gland-like structures, which came about as a response to the displacement of the sperm and fluid. The exact cause of his ruptured sperm granuloma was not determined, but it was found to be most likely a secondary response to inflammation and/or trauma. [ 13 ]


Another complication with sperm granulomas has been being mistaken for a tumor due to its tumor-like appearance. [ 14 ]  A 45 year old man presented with right testicular chronic pain. He had a vasectomy 7 years ago. Upon physical examination and an ultrasound, a solid nodule in the right epididymis was found, and medical staff suspected a tumor. After findings of sperm that had undergone phagocytosis, a final diagnosis of sperm granuloma was determined.  [ 14 ]


It is unknown whether sperm granulomas are definitively detrimental to sperm quality and fertility in humans. However, studies in donkeys have shown that sperm quality is only marginally affected. There was a lower percentage of sperm with intact plasma membranes; however, no effects on motility or morphology were observed. [ 15 ]  In some cases, the presence or absence of sperm granulomas may determine the success rate for vasectomy reversal.


It is believed that sperm granulomas may be protective because they can prevent the obstruction of the testicles and epididymis. [ 16 ]  Sperm granulomas are believed to reduce the pressure that is generated after vasectomy and prevent blockages of sperm output into the vas fluid during ejaculation. Therefore, there are no changes in the amount of sperm that are produced into the vas fluid. [ 16 ]


Additionally, sperm granulomas can exist in non-human species such as rats, dogs, horses, fish, etc. Non-human species exhibit the same causes for sperm granulomas, including infection, injury, and trauma to the epididymal region. For example, vasectomized rats were seen to also have a high prevalence of sperm granulomas post-operation while general populations of rats experienced a much lower prevalence of sperm granulomas. [ 17 ]  In the case of sperm granulomas within dogs, their presence is common amongst poorly performed vasectomies. [ 12 ]  This is consistent with the idea that these lesions form at the site where there is trauma or a chance for the sperm to leak outside of the vasa deferentia or epididymis. In multiple species, sperm granulomas have also been linked to the success rate of certain procedures such as vasectomy reversals, or  vasovasostomy . [ 12 ]  There is also an association between sperm granuloma and antibodies produced against sperm antigens. In a case study on sperm granuloma and anti-sperm antibody count in donkeys, it was found that sperm granuloma resulted in an increase in IgA- and IgG-bound sperm in donkeys. They also found donkeys with sperm granuloma had a reduction of sperm motility and a reduction of the percentage of sperm with an intact plasma membrane. However there was no significant damage found in total sperm motility compared to healthy control donkeys. The extent to which sperm granuloma and anti-sperm antibodies affect donkey fertility is still yet to be determined by further research studies.


The Stork Club  ( ISBN   0593056086 ) is a  2006  book by British author and journalist  Imogen Edwards-Jones . [ 1 ]  The book, based on the author’s  Daily Telegraph  column "Shall I Be a Mother?", [ citation needed ]  is an autobiographical account of Edward-Jones’ attempts to conceive. The book outlines Imogen Edwards-Jones’ treatment by  IVF . [ 1 ]


This article about a biographical or autobiographical book is a  stub . You can help Wikipedia by  expanding it .


Lesbian ,  gay ,  bisexual , and  transgender  people ( LGBT community ) people wishing to have children may use  assisted reproductive technology . In recent decades, developmental biologists have been researching and developing techniques to facilitate same-sex reproduction. [ 1 ]


The obvious [ clarification needed ]  approaches, subject to a growing amount of activity, are  female sperm  and  male eggs . In 2004, by altering the function of a few genes involved with imprinting, other Japanese scientists combined two mouse eggs to produce daughter mice [ 2 ]  and in 2018 Chinese scientists created 29 female mice from two female mice mothers but were unable to produce viable offspring from two father mice. [ 3 ] [ 4 ]  One of the possibilities is transforming skin  stem cells  into sperm and eggs. [ 5 ]


Lack of access to assisted reproductive technologies is a form of  healthcare inequality  experienced by LGBT people. [ 6 ]


LGBT women and  trans men  may choose to donate their  eggs  in order to reproduce by  in-vitro fertilization . Trans men in particular may freeze their eggs before transitioning and choose to have a female surrogate carry their child while when the time comes, using their eggs and someone else's sperm. This allows them to avoid the potentially dysphoria-triggering experience of pregnancy, or cessation of HRT for collecting eggs at an older age. [ 7 ]


Cryopreservation  of  oocytes  (eggs) requires hormonal stimulation and oocyte retrieval, as for IVF treatment, after which the oocytes are  vitrified . [ 8 ]   Vitrification of oocytes has been found to be more successful than slow freezing oocytes. [ 9 ]  The success of oocyte banking declines significantly with increasing reproductive age. [ 10 ]  Ovarian stimulation will increase transgender men's serum estradiol levels, and in response transvaginal ultrasound monitoring may be necessary, strategies to minimize estradiol elevations include the concomitant use of aromatase inhibitors during stimulation. [ 11 ]  There is no data on the success of ovarian stimulation in transgender men who previously had puberty halted with GnRH agonist, followed directly by testosterone administration. [ 11 ]  There is also no data comparing the number of oocytes retrieved or the live-birth rate after fertility preservation stratified by time off testosterone. [ 12 ]


A surgical procedure is required to collect tissue samples, if undergoing a  hysterectomy  and/or ovariectomy, one can choose to cryopreserve some tissue at the same time to avoid an additional surgical procedure. [ 8 ]  Ovarian tissue cryopreservation has been successful, but so far [ as of? ] , there have been no pregnancies recorded after thawing and in-vitro maturation (IVM) of this tissue, successful pregnancies have only been recorded after  auto-transplantation . [ 13 ] [ 8 ]  This method has a very low success rate of  blastocyst  development as in one study of 83 transgender males, 2 out of the 208 mature oocytes were recovered from thawed ovarian tissue created "good-quality" blastocysts. [ 12 ]


For the purposes of either  in-vitro fertilization  or  artificial insemination , LGBT individuals may choose to preserve their eggs or sperm.


Trans women may have lower sperm quality before HRT, which may pose an issue for creating viable sperm samples to freeze. [ 14 ]


Estrogens suppress testosterone levels and at high doses can markedly disrupt sex drive and function and fertility on their own. [ 15 ] [ 16 ] [ 17 ] [ 18 ] [ needs update ]  Moreover, disruption of gonadal function and fertility by estrogens may be permanent after extended exposure. [ 17 ] [ 18 ] [ 19 ]


Nonsteroidal antiandrogens like  bicalutamide  may be an option for transgender women who wish to preserve  sex drive ,  sexual function , and/or  fertility , relative to antiandrogens that suppress testosterone levels and can greatly disrupt these functions such as cyproterone acetate and GnRH modulators. [ 20 ] [ 21 ]


Semen can be collected via masturbation, but there are alternatives for those who find masturbation or ejaculation distressing or may have erectile or  ejaculatory dysfunction  secondary to  hypoandrogenism . Options for those with dysfunction include:  penile vibratory stimulation  and  electroejaculation . [ 11 ]  For those who do not want to ejaculate or have oligospermia or azoospermia can pursue  testicular sperm aspiration  or microsurgical sperm extraction although they are more invasive. [ 11 ]  There are currently no studies evaluating the acceptability or success rates of the different options for sperm collection specifically in transgender women. [ 11 ]  Furthermore, for transgender women on estradiol and/or antiandrogens, it is unclear the length of time needed to be off hormonal treatment medication before normal spermatogenesis resumes (if it occurs at all), during which time testosterone production will resume and may cause unwanted masculinizing effects. [ 11 ]


Prospective LGBT parents may have pick sperm from a  sperm bank  to grow their baby. The sperm can come from one partner, either having been frozen before their  transition , or being recent in the case of a partner having  functioning male organs . Other times, it can come from private  sperm donors .
LGBT individuals must carefully consider where they get their donor sperm from. Individual state's laws vary, but many U.S. states have adopted a form of the  Uniform Parentage Act  (UPA). [ 22 ]  Most, but not all states transfer parental rights from anonymous  sperm donors  to the intended parents as long as the recipient is a married woman, and a physician is involved. [ 22 ]  Noncompliance with these laws can result in the failure to terminate sperm donor parental rights. There have been court cases where known sperm donors that privately donated directly were requested to pay  child support . [ 22 ] [ 23 ] [ 24 ] [ 25 ]  For example, of these laws, see  California assisted reproductive laws . In Australia, there has been legal precedent that sperm donor involvement with the ensuing child's life does grant them parental rights (Masson v Parsons). [ 26 ]


Alternative to direct private donation it is possible to purchase sperm from a  sperm bank  for personal use in fertility treatment. Sperm banks can vary widely, not only in terms of price, but of practice (i.e. who is allowed to donate sperm, how many times, etc.) and can offer a variety of services. Major U.S. sperm banks include Fairfax Cryobank,  California Cyrobank ,  Cryos International , Seattle Sperm bank, and Xytex, and many others.


In order to accommodate for different  gender identities  and  sexual orientations , a LGBT pregnancy from donated sperm can be done through artificial insemination. It is putting the donated sperm inside the body of the carrying womb ( surrogate pregnancy  or other).


Timing of these procedures are critical for successful fertilization, [ 27 ]  as the fertile window is the five days before ovulation, plus the day of and after ovulation. [ 28 ]  To increase the chance of success, the menstrual cycle is closely observed, often using ovulation kits, ultrasounds or blood tests, such as  basal body temperature  tests over, noting the color and texture of the vaginal mucus, and the softness of the nose of the cervix. [ 28 ]  To improve the success rate of artificial insemination, drugs to create a  stimulated cycle  may be used called  ovarian stimulation  (OS).


Before ovulation there is a surge of luteinizing hormone (LH) which can be used to time an IUI procedure. Data suggest that IUI should be performed 1 day after the detection of the LH surge. [ 27 ]  Most clinics in the U.S. perform IUI in the morning after a positive ovulation predictor kit test (which detects LH in urine). [ 27 ]  An alternative to LH monitoring is ultrasound monitoring of ovarian follicle size followed by a trigger shot with exogenous human chorionic gonadotropin (hCG) which mimics the body's LH surge and triggers final follicular maturation and rupture (36–48 hours later). The trigger shot is typically administered when the dominant follicle reaches 18–20 mm. [ 27 ]  The recommended timing of IUI after hCG administration is 24–40 hours. [ 27 ]   IUI cycles stimulated with classical doses of FSH have a high rate of have a multiple pregnancy with rates ranging from 10 to 40%. [ 29 ]   A meta-analysis showed no difference between pregnancy outcomes between at-home LH monitoring and timed IUI. [ 27 ]


IUI can be done without the use of medication. IUI is not recommended in cases where the gestating individuals have cervical atresia, cervicitis, endometritis or bilateral tubal obstruction or when the sperm donor has amenorrhea or severe oligospermia. [ 29 ]  Prior to IUI, the sperm is "washed" which is necessary to remove seminal plasma to avoid prostaglandin-induced uterine contractions. [ 29 ]  Insemination with unprocessed semen is also associated with pelvic infection. [ 29 ]