Female infertility
Encyclopedia
Causes and factors
Causes or factors of female infertility can basically be classified regarding whether they are acquiredAcquired disorder
An acquired disorder is a medical condition which develops post-fetally; in contrast with a congenital disorder, which is present at birth. A congenital disorder may be antecedent to an acquired disorder ....
or genetic, or strictly by location.
Acquired versus genetic
Although causes (or factors) of female infertility can be classified as acquired versus genetic, female infertility is usually more or less a combination of nature and nurture. Also, the presence of any single risk factorRisk factor
In epidemiology, a risk factor is a variable associated with an increased risk of disease or infection. Sometimes, determinant is also used, being a variable associated with either increased or decreased risk.-Correlation vs causation:...
of female infertility (such as smoking, mentioned further below) does not necessarily cause infertility, and even if a woman is definitely infertile then the infertility cannot definitely be blamed on any single risk factor even if the risk factor is (or has been) present.
Acquired
According to the American Society for Reproductive Medicine (ASRM), Age, Smoking, Sexually Transmitted Infections, and Being Overweight or Underweight can all affect fertility.In broad sense, acquired factors practically include any factor that is not based on a genetic mutation, including any intrauterine exposure to toxins during fetal development
Environmental toxins and fetal development
It has long been known that the fetus can be sensitive to impacts from adverse environmental exposures. Fetal development can be affected by exposures that occur to either parent prior to conception and to the mother post conception.-Fetal development:...
, which may present as infertility many years later as an adult.
Age
Women become less fertile as they get older. A woman's fertility peaks between the ages of 22 to 26, after which it starts to decline, with this decline being accelerated after age 35. However, the exact estimates of the chances of a woman to conceive after a certain age are not clear, with research giving differing results. The chances of a couple to successfully conceive at an advanced age depend on many factors, such as the general health of a woman, but also the fertility of the male partner.
According to the National Institute for Health and Clinical Excellence
National Institute for Health and Clinical Excellence
The National Institute for Health and Clinical Excellence is a special health authority of the English National Health Service , serving both English NHS and the Welsh NHS...
, for women aged 35, about 94 out of every 100 who have regular unprotected sexual intercourse will get pregnant after 3 years of trying. For women aged 38, however, only 77 out of every 100 will do so.
In 1957, a study was done on a large population that never used birth control. The investigators measured the relationship between the age of the female partner and fertility. (Infertility rates today are believed to be higher in the general population than for the population in this study from the 1950s).
This 1957 study found that :
- By age 30, 7% of couples were infertile
- By age 35, 11% of couples were infertile
- By age 40, 33% of couples were infertile
- At age 45, 87% of couples were infertile
According to Henri Leridon, PhD, an epidemiologist with the French Institute of Health and Medical Research,
of women trying to get pregnant, without using fertility drugs or in vitro fertilization:
- At age 30
- 75% will have a conception ending in a live birth within one year
- 91% will have a conception ending in a live birth within four years.
- At age 35
- 66% will have a conception ending in a live birth within one year
- 84% will have a conception ending in a live birth within four years.
- At age 40
- 44% will have a conception ending in a live birth within one year
- 64% will have a conception ending in a live birth within four years.
According to a study done on a sample of 782 healthy European couples ages 19–39, fertility starts declining after age 27 and drops at a somewhat greater rate after age 35. The women were divided into four age groups: 19-26, 27-29, 30-34 and 35-39. Statistical analysis showed that the women in the 27-29 age group had significantly less chance on average of becoming pregnant than did the 19-26-year olds. Pregnancy rates did not change notably between the 27-29 age group and the 30-34 age group, but dropped sharply for women over 35. The age of the male partner had a significant impact on female fertility among the women who had reached their mid-30s, but not among the younger women. However experts said the new study was too small and there were too many variables which were too difficult to sort out, for a clear conclusion to be drawn. Some experts suggested that the main change in fertility in the older women was the fact that it took them longer to conceive, not necessary that they were significantly more unlikely to eventually succeed. David Dunson, a biostatistician at the U.S. National Institute of Environmental Health Sciences, said that: "Although we noted a decline in female fertility in the late 20s, what we found was a decrease in the probability of becoming pregnant per menstrual cycle, not in the probability of eventually achieving a pregnancy."
In terms of ovarian reserve
Ovarian reserve
Ovarian reserve is a term that is used to determine the capacity of the ovary to provide eggs that are capable of fertilization resulting in a healthy and successful pregnancy...
, a typical woman has 12% of her reserve at age 30 and has only 3% at age 40. 81% of variation in ovarian reserve is due to age alone, making age the most important factor in female infertility.
Some experts assert that the average woman's fertility peaks when she is 24 years of age.
However a French study found no difference between the fertility rate of women under 25 and those aged 26–30, after which fertility started to decrease. Estimating the "fertility of a woman" is quite difficult because of the male factor (quality of sperm). This French study looked at 2,193 women who were using artificial insemination
Artificial insemination
Artificial insemination, or AI, is the process by which sperm is placed into the reproductive tract of a female for the purpose of impregnating the female by using means other than sexual intercourse or natural insemination...
because their husbands were azoospermic. The cumulative success rates after 12 cycles of insemination were 73% for women under age 25, 74% in women aged 26–30, 61% for ages 31–35, and 54% in the over 35 age group. (note however that the study is from 1982, artificial insemination techniques and success rates have evolved greatly since then).
In Hungary, a study by the Statisztikai Hivatal (Central Statistics Office) estimated that 7-12% of Hungarian women younger than 30 were infertile; 13-22% of women aged 35 were infertile; and 24-46% of women aged 40 were infertile.
A study by Fong, S. and McGovern, P. suggests that among women aged 35–39, about 1 in 3 have fertility problems.
Most IVF centers will attempt IVF using the female partner's own eggs until about age 43-45. Michael Fox, M.D., a Reproductive Endocrinologist with North Florida Gynecologic Specialists in Jacksonville, states that, with regard to assisted reproduction treatment, "in general our approach to treatment of patients over age 35 is vastly more aggressive than in younger patients".
A study commissioned by RESOLVE, a non-profit patient advocacy organization, states that both three out of four men and three out of four women overestimate by five years the rapid decline in female fecundity with prime childbearing age occurring up to age 32 for females and a rapid decline at 35 instead of 40 as most people commonly believe. The American Society for Reproductive Medicine (ASRM) states, "...women in their 20's to early 30's are most likely to conceive." and in greater detail newsletter: (Even more detailed booklet:). Elite egg donor agencies such as A Perfect Match that advertise in places such as Ivy League student newspapers offering up to $20,000 or even $50,000 for donor eggs seek donors under the age of 29.
Fertility specialist and book author Dr. Sherman Silber
Sherman Silber
Sherman J. Silber is a pioneer in the field of infertility. He invented many of the infertility treatments in use today, and is considered a foremost authority on IVF, sperm retrieval, ICSI, vasectomy reversal, tubal ligation reversal, egg and embryo freezing, ovary transplantation, and the...
states, in a message to women (A Special Message From Dr. Silber About Your Biological Clock and Preserving Your Fertility) that "almost 25% of all women of childbearing age currently wishing to have children are infertile" and "Only 1% of women in their early 20’s are infertile but by their late 20’s, 16% [one in six] are infertile, and by their mid-30’s almost 25% [one in four] are infertile. By age 40, 60% [three in five] are infertile and by age 43 it would be a rare woman who is still fertile," (however Dr. Sherman Silber does not explain what definition of "infertility" he is referring to, and in the US the most common definition is a woman under 35 who has not conceived in 12 months and a woman over 35 who has not conceived in 6 months, a definition which has been criticized as being based on public policy - as after this period women are advised to seek medical intervention; the NICE does not accept this definition and its guidelines define infertility as failure to conceive after regular unprotected sexual intercourse for 2 years in the absence of known reproductive pathology). Because one in six can be infertile (before treatment) by their late 20's Dr. Silber recommends that a woman who expects to delay childbirth beyond age 30 have her gynecologist perform an antral follicle count ultrasound at about age 25. Other fertility specialists such as book author Dr. Daniel Potter recommend an FSH (Follicle-stimulating hormone
Follicle-stimulating hormone
Follicle-stimulating hormone is a hormone found in humans and other animals. It is synthesized and secreted by gonadotrophs of the anterior pituitary gland. FSH regulates the development, growth, pubertal maturation, and reproductive processes of the body. FSH and Luteinizing hormone act...
) or other laboratory test instead of the antral follicle count ultrasound.
The issues of age need to be taken up with a qualified fertility specialist such as a reproductive endocrinologist. Standard of care: Women over 35 who are attempting to conceive should seek the advice of a fertility specialist after six months of unprotected intercourse, or after one year if under the age of 35.
Tobacco smoking
Tobacco smoking
Tobacco smoking
Tobacco smoking is the practice where tobacco is burned and the resulting smoke is inhaled. The practice may have begun as early as 5000–3000 BCE. Tobacco was introduced to Eurasia in the late 16th century where it followed common trade routes...
is harmful to the ovaries, and the degree of damage is dependent upon the amount and length of time a woman smokes. Nicotine and other harmful chemicals in cigarettes interfere with the body’s ability to create estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
, a hormone that regulates folliculogenesis
Folliculogenesis
In biology, folliculogenesis is the maturation of the ovarian follicle, a densely-packed shell of somatic cells that contains an immature oocyte...
and ovulation
Ovulation
Ovulation is the process in a female's menstrual cycle by which a mature ovarian follicle ruptures and discharges an ovum . Ovulation also occurs in the estrous cycle of other female mammals, which differs in many fundamental ways from the menstrual cycle...
. Also, cigarette smoking interferes with folliculogenesis, embryo transport, endometrial receptivity, endometrial angiogenesis, uterine blood flow and the uterine myometrium. Some damage is irreversible, but stopping smoking can prevent further damage. Smokers are 60% more likely to be infertile than non-smokers. Smoking reduces the chances of IVF producing a live birth by 34% and increases the risk of an IVF pregnancy miscarrying by 30%. Also, female smokers have an earlier onset of menopause
Menopause
Menopause is a term used to describe the permanent cessation of the primary functions of the human ovaries: the ripening and release of ova and the release of hormones that cause both the creation of the uterine lining and the subsequent shedding of the uterine lining...
by approximately 1–4 years.
Sexually transmitted disease
Sexually transmitted diseases
Sexually transmitted disease
Sexually transmitted disease , also known as a sexually transmitted infection or venereal disease , is an illness that has a significant probability of transmission between humans by means of human sexual behavior, including vaginal intercourse, oral sex, and anal sex...
are a leading cause of infertility. They often display few, if any visible symptoms, with the risk of failing to seek proper treatment in time to prevent decreased fertility.
Body weight and eating disorders
Twelve percent of all infertility cases are a result of a woman either being underweight
Underweight
The term underweight refers to a human who is considered to be under a healthy weight. "Underweight" means weighing less than what is expected to be a healthy person . The definition is usually made with reference to the body mass index . A BMI of under 18.5 is usually referred to as underweight...
or overweight
Overweight
Overweight is generally defined as having more body fat than is optimally healthy. Being overweight is a common condition, especially where food supplies are plentiful and lifestyles are sedentary...
. Fat cells
Adipocyte
However, in some reports and textbooks, the number of fat cell increased in childhood and adolescence. The total number is constant in both obese and lean adult...
produce estrogen, in addition to the primary sex organ
Sex organ
A sex organ, or primary sexual characteristic, as narrowly defined, is any of the anatomical parts of the body which are involved in sexual reproduction and constitute the reproductive system in a complex organism; flowers are the reproductive organs of flowering plants, cones are the reproductive...
s. Too much body fat causes production of too much estrogen and the body begins to react as if it is on birth control, limiting the odds of getting pregnant. Too little body fat causes insufficient production of estrogen and disruption of the menstrual cycle
Menstrual cycle
The menstrual cycle is the scientific term for the physiological changes that can occur in fertile women for the purpose of sexual reproduction. This article focuses on the human menstrual cycle....
. Both under and overweight women have irregular cycles in which ovulation does not occur or is inadequate. Proper nutrition in early life is also a major factor for later fertility.
A study in the US indicated that approximately 20% of infertile women had a past or current eating disorder, which is five times higher than the general lifetime prevalence rate.
A review from 2010 concluded that overweight and obese subfertile women have a reduced probability of successful fertility treatment and their pregnancies are associated with more complications and higher costs. In hypothetical groups of 1000 women undergoing fertility care, the study counted approximately 800 live births for normal weight and 690 live births for overweight and obese anovulatory women. For ovulatory women, the study counted approximately 700 live births for normal weight, 550 live births for overweight and 530 live births for obese women. The increase in cost per live birth in anovulatory overweight and obese women were, respectively, 54 and 100% higher than their normal weight counterparts, for ovulatory women they were 44 and 70% higher, respectively.
Chemotherapy
Chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
poses a high risk of infertility. Antral follicle count decreases after three series of chemotherapy, whereas follicle stimulating hormone (FSH) reaches menopausal levels after four series. Other hormonal changes in chemotherapy include decrease in inhibin B and anti-Müllerian hormone
Anti-müllerian hormone
Anti-Müllerian hormone also known as AMH is a protein that, in humans, is encoded by the AMH gene. It inhibits the development of the Müllerian ducts in the male embryo. It has also been called Müllerian inhibiting factor , Müllerian-inhibiting hormone , and Müllerian-inhibiting substance...
levels. Chemotherapies with high risk of infertility include procarbazine and other alkylating drugs such as cyclophosphamide, ifosfamide, busulfan, melphalan, chlorambucil and chlormethine. Drugs with medium risk include doxorubicin and platinum analogs such as cisplatin and carboplatin. On the other hand, therapies with low risk of gonadotoxicity include plant derivatives such as vincristine and vinblastine, antibiotics such as bleomycinand dactinomycin and antimetabolites such as methotrexate, mercaptopurine and 5-fluoruracil.
Patients may choose between several methods of fertility preservation
Fertility preservation
Fertility preservation is the effort to help cancer patients retain their fertility, or ability to procreate. Research into how cancer affects reproductive health and preservation options are growing, sparked in part by the increase in the survival rate of cancer patients.-Indications:Fertility...
prior to chemotherapy, including cryopreservation
Cryopreservation
Cryopreservation is a process where cells or whole tissues are preserved by cooling to low sub-zero temperatures, such as 77 K or −196 °C . At these low temperatures, any biological activity, including the biochemical reactions that would lead to cell death, is effectively stopped...
of ovarian tissue, oocytes or embryos.
Other factors that can cause acquired infertility
- Significant liverLiverThe liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
or kidneyKidneyThe kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
disease - ThrombophiliaThrombophiliaThrombophilia is an abnormality of blood coagulation that increases the risk of thrombosis . Such abnormalities can be identified in 50% of people who have an episode of thrombosis that was not provoked by other causes...
- Cannabis smokingCannabis smokingCannabis smoking involves inhaling vapors released by heating the flowers and subtending leaves of the Cannabis plants, known as marijuana. Alternatively, the cannabis plant flowers may be finely sifted producing kief, a powder especially rich in the oil-glands or trichomes which contain the...
, such as of marijuana causes disturbances in the endocannabinoid systemEndocannabinoid systemThe endocannabinoid system refers to a group of neuromodulatory lipids and their receptors that are involved in a variety of physiological processes including appetite, pain-sensation, mood, and memory; it mediates the psychoactive effects of cannabis and, broadly speaking, includes:* The...
, potentially causing infertility
Genetic factors
There are many geneGene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s wherein mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
causes female infertility, as shown in table below. Also, there are additional conditions involving female infertility which are believed to be genetic but where no single gene has been found to be responsible, notably Mayer-Rokitansky-Küstner-Hauser Syndrome (MRKH). Finally, an unknown number of genetic mutations cause a state of subfertility, which in addition to other factors such as environmental ones may manifest as frank infertility.
Chromosomal abnormalities causing female infertility include Turner syndrome
Turner syndrome
Turner syndrome or Ullrich-Turner syndrome encompasses several conditions in human females, of which monosomy X is most common. It is a chromosomal abnormality in which all or part of one of the sex chromosomes is absent...
.
Some of these gene or chromosome abnormalities cause intersexed conditions, such as androgen insensitivity syndrome
Androgen insensitivity syndrome
Androgen insensitivity syndrome is a condition that results in the partial or complete inability of the cell to respond to androgens. The unresponsiveness of the cell to the presence of androgenic hormones can impair or prevent the masculinization of male genitalia in the developing fetus, as...
| Gene | Encoded protein | Effect |
|---|---|---|
| BMP15 | Bone morphogenetic protein 15 Bone morphogenetic protein 15 Bone morphogenetic protein 15 is a protein that in humans is encoded by the BMP15 gene.The protein encoded by this gene is a member of the TGF-β superfamily. It is a paracrine signaling molecule involved in oocyte and follicular development. Using Northern blot analysis, BMP15 has been shown to be... |
Hypergonadotrophic ovarian failure (POF4) |
| BMPR1B BMPR1B Bone morphogenetic protein receptor type-1B also known as CDw293 is a protein that in humans is encoded by the BMPR1B gene.- Function :... |
Bone morphogenetic protein receptor 1B | Ovarian dysfunction, hypergonadotrophic hypogonadism and acromesomelic chondrodysplasia |
| CBX2 CBX2 (gene) Chromobox protein homolog 2 is a protein that in humans is encoded by the CBX2 gene. According to a New Scientist CBX2 controls human gender even more so than X/Y chromosomes.-Interactions:CBX2 has been shown to interact with RYBP.... ; M33 M33 (gene) M33 is a gene. It is a mammalian homologue of Drosophila Polycomb. It localises to euchromatin within interphase nuclei but is enriched within the centromeric heterochromatin of metaphase chromosomes.... |
Chromobox protein homolog 2 ; Drosophila polycomb class | Autosomal 46,XY, male-to-female sex reversal (phenotypically perfect females) |
| CHD7 CHD7 Chromodomain-helicase-DNA-binding protein 7 also known as ATP-dependent helicase CHD7 is an enzyme that in humans is encoded by the CHD7 gene.... |
Chromodomain-helicase-DNA-binding protein 7 | CHARGE syndrome CHARGE syndrome CHARGE syndrome , is a syndrome caused by a genetic disorder. It was first described in 1979.In 1981, the term "CHARGE" came into use as an acronym for the set of unusual congenital features seen in a number of newborn children... and Kallmann syndrome Kallmann syndrome Kallmann syndrome is a genetic disorder marked by anosmia and hypogonadism - the decreased functioning of the glands that produce sex hormones. Abnormalities in various genes may cause a defect in the hypothalamus, causing a deficiency of gonadotropin-releasing hormone ; this in turn causes... (KAL5) |
| DIAPH2 DIAPH2 Protein diaphanous homolog 2 is a protein that in humans is encoded by the DIAPH2 gene.-Further reading:... |
Diaphanous homolog 2 | Hypergonadotrophic, premature ovarian failure (POF2A) |
| FGF8 FGF8 Fibroblast growth factor 8 is a protein that in humans is encoded by the FGF8 gene.-External links:*... |
Fibroblast growth factor 8 | Normosmic hypogonadotrophic hypogonadism and Kallmann syndrome (KAL6) |
| FGFR1 | Fibroblast growth factor receptor 1 Fibroblast growth factor receptor 1 Fibroblast growth factor receptor 1 , also known as basic fibroblast growth factor receptor 1, fms-related tyrosine kinase-2 / Pfeiffer syndrome, and CD331, is a receptor tyrosine kinase whose ligands are specific members of the fibroblast growth factor family... |
Kallmann syndrome (KAL2) |
| FSHR | FSH receptor | Hypergonadotrophic hypogonadism and ovarian hyperstimulation syndrome |
| FSHB FSHB Follitropin subunit beta is a protein that in humans is encoded by the FSHB gene.-Further reading:... |
Follitropin subunit beta | Deficiency of follicle-stimulating hormone, primary amenorrhoea and infertility |
| FOXL2 | Forkhead box L2 Forkhead box L2 Forkhead box protein L2 is a protein that in humans is encoded by the FOXL2 gene.- Function :FOXL2 is a forkhead transcription factor. The protein contains a fork-head DNA-binding domain and may play a role in ovarian development and function.... |
Isolated premature ovarian failure (POF3) associated with BPES type I; FOXL2 402C --> G mutations associated with human granulosa cell tumours |
| FMR1 FMR1 FMR1 is a human gene that codes for a protein called fragile X mental retardation protein, or FMRP. This protein, most commonly found in the brain, is essential for normal cognitive development and female reproductive function... |
Fragile X mental retardation | Premature ovarian failure (POF1) associated with premutations |
| GNRH1 | Gonadotropin releasing hormone | Normosmic hypogonadotrophic hypogonadism |
| GNRHR GNRHR Gonadotropin-releasing hormone receptor is a protein that in humans is encoded by the GNRHR gene.-Further reading:... |
GnRH receptor | Hypogonadotrophic hypogonadism |
| KAL1 | Kallmann syndrome | Hypogonadotrophic hypogonadism and insomnia, X-linked Kallmann syndrome (KAL1) |
| KISS1R ; GPR54 | KISS1 receptor | Hypogonadotrophic hypogonadism |
| LHB Luteinizing hormone beta polypeptide Lutropin subunit beta is a protein that in humans is encoded by the LHB gene.-Further reading:... |
Luteinizing hormone beta polypeptide Luteinizing hormone beta polypeptide Lutropin subunit beta is a protein that in humans is encoded by the LHB gene.-Further reading:... |
|
| LHCGR | LH/choriogonadotrophin receptor | Hypergonadotrophic hypogonadism (luteinizing hormone resistance) |
| DAX1 DAX1 DAX1 is a nuclear receptor protein that in humans is encoded by the NR0B1 gene... |
Dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1 | X-linked congenital adrenal hypoplasia with hypogonadotrophic hypogonadism; dosage-sensitive male-to-female sex reversal |
| NR5A1; SF1 SF1 (gene) Splicing factor 1 also known as zinc finger protein 162 is a protein that in humans is encoded by the SF1 gene.Splicing factor SF1 is involved in the ATP-dependent formation of the spliceosome complex.-Interactions:... |
Steroidogenic factor 1 Steroidogenic factor 1 The steroidogenic factor 1 protein controls sexual development in the embryo and at puberty.SF1 is a member of the nuclear receptor family of intracellular transcription factors and is encoded by the NR5A1 gene .- Function :SF-1 is a critical regulator of reproduction, regulating the transcription... |
46,XY male-to-female sex reversal and streak gonads and congenital lipoid adrenal hyperplasia; 46,XX gonadal dysgenesis and 46,XX primary ovarian insufficiency |
| POF1B POF1B Protein POF1B is a protein that in humans is encoded by the POF1B gene.-Further reading:... |
Premature ovarian failure 1B | Hypergonadotrophic, primary amenorrhea (POF2B) |
| PROK2 | Prokineticin Prokineticin Prokineticin is a secreted protein that potently contracts gastrointestinal smooth muscle. Recently, Prokineticins have been recognized in humans and other vertebrates. They are thought to be involved in several important physiological processes like neurogenesis, tissue development, angiogenesis,... |
Normosmic hypogonadotrophic hypogonadism and Kallmann syndrome (KAL4) |
| PROKR2 | Prokineticin receptor 2 Prokineticin receptor 2 Prokineticin receptor 2 , in a G-protein coupled receptor encoded by the PROKR2 gene in humans.-External links:* -Further reading:... |
Kallmann syndrome (KAL3) |
| RSPO1 RSPO1 R-spondin-1 is a protein that in humans is encoded by the RSPO1 gene.-Further reading:... |
R-spondin family, member 1 | 46,XX, female-to-male sex reversal (individuals contain testes) |
| SRY SRY SRY is a sex-determining gene on the Y chromosome in the therians .This intronless gene encodes a transcription factor that is a member of the SOX gene family of DNA-binding proteins... |
Sex-determining region Y | Mutations lead to 46,XY females; translocations lead to 46,XX males |
| SOX9 SOX9 Transcription factor SOX-9 is a protein that in humans is encoded by the SOX9 gene.- Function :SOX-9 recognizes the sequence CCTTGAG along with other members of the HMG-box class DNA-binding proteins... |
SRY-related HMB-box gene 9 | Autosomal 46,XY male-to-female sex reversal (campomelic dysplasia) |
| TAC3 TAC3 Tachykinin-3 is a protein that in humans is encoded by the TAC3 gene.-Further reading:... |
Tachykinin 3 | Normosmic hypogonadotrophic hypogonadism |
| TACR3 | Tachykinin receptor 3 Tachykinin receptor 3 Tachykinin receptor 3, also known as TACR3, is a protein which in humans is encoded by the TACR3 gene.- Function :This gene belongs to a family of genes that function as receptors for tachykinins. Receptor affinities are specified by variations in the 5'-end of the sequence... |
Normosmic hypogonadotrophic hypogonadism |
Ovarian factors
- Polycystic ovary syndromePolycystic ovary syndromePolycystic ovary syndrome is one of the most common female endocrine disorders. PCOS is a complex, heterogeneous disorder of uncertain aetiology, but there is strong evidence that it can to a large degree be classified as a genetic disease....
,
- AnovulationAnovulationAn anovulatory cycle is a menstrual cycle during which the ovaries do not release an oocyte. Therefore, ovulation does not take place. However, a woman who does not ovulate at each menstrual cycle is not necessarily going through menopause...
. Female infertility caused by anovulation is called "anovulatory infertility", as opposed to "ovulatory infertility" in which ovulation is present.
- Diminished ovarian reserveOvarian reserveOvarian reserve is a term that is used to determine the capacity of the ovary to provide eggs that are capable of fertilization resulting in a healthy and successful pregnancy...
, also see Poor Ovarian ReservePoor ovarian reservePoor ovarian reserve is a condition of low fertility characterized by 1): low numbers of remaining oocytes in the ovaries or 2) possibly impaired preantral oocyte development or recruitment...
- Premature menopause
- MenopauseMenopauseMenopause is a term used to describe the permanent cessation of the primary functions of the human ovaries: the ripening and release of ova and the release of hormones that cause both the creation of the uterine lining and the subsequent shedding of the uterine lining...
- Luteal dysfunction
- Gonadal dysgenesis (Turner syndromeTurner syndromeTurner syndrome or Ullrich-Turner syndrome encompasses several conditions in human females, of which monosomy X is most common. It is a chromosomal abnormality in which all or part of one of the sex chromosomes is absent...
)
- Ovarian cancerOvarian cancerOvarian cancer is a cancerous growth arising from the ovary. Symptoms are frequently very subtle early on and may include: bloating, pelvic pain, difficulty eating and frequent urination, and are easily confused with other illnesses....
Tubal (ectopic)/peritoneal factors
- EndometriosisEndometriosisEndometriosis is a gynecological medical condition in which cells from the lining of the uterus appear and flourish outside the uterine cavity, most commonly on the ovaries. The uterine cavity is lined by endometrial cells, which are under the influence of female hormones...
Endometriosis can lead to anatomical distortions and adhesionsAdhesion (medicine)Adhesions are fibrous bands that form between tissues and organs, often as a result of injury during surgery. They may be thought of as internal scar tissue that connect tissues not normally connected.-Pathophysiology:...
(the fibrous bands that form between tissues and organs following recovery from an injury). However, the link between infertility and endometriosis remains enigmatic when the extent of endometriosis is limited. It has been suggested that endometriotic lesions release factors which are detrimental to gametes or embryos, or, alternatively, endometriosis may more likely develop in women who fail to conceive for other reasons and thus be a secondary phenomenon; for this reason it is preferable to speak of endometriosis-associated infertility in such cases.
- Pelvic adhesionsAdhesion (medicine)Adhesions are fibrous bands that form between tissues and organs, often as a result of injury during surgery. They may be thought of as internal scar tissue that connect tissues not normally connected.-Pathophysiology:...
- Pelvic inflammatory diseasePelvic inflammatory diseasePelvic inflammatory disease is a generic term for inflammation of the uterus, fallopian tubes, and/or ovaries as it progresses to scar formation with adhesions to nearby tissues and organs. This may lead to infections. PID is a vague term and can refer to viral, fungal, parasitic, though most...
(PID, usually due to chlamydia)
- Tubal occlusion
- Tubal dysfunction
Uterine factors
- Uterine malformationUterine malformationA uterine malformation is a type of female genital malformation resulting from an abnormal development of the Müllerian duct during embryogenesis...
s
- Uterine fibroids (leiomyomaLeiomyomaA leiomyoma is a benign smooth muscle neoplasm that is not premalignant. They can occur in any organ, but the most common forms occur in the uterus, small bowel and the esophagus.- Etymology:* Greek:** λεῖος leios "smooth"...
)
- Asherman's SyndromeAsherman's syndromeAsherman's syndrome , also called "uterine synechiae" or intrauterine adhesions , presents a condition characterized by the presence of adhesions and/or fibrosis within the uterine cavity due to scars...
Cervical factors
- Cervical stenosisStenosis of uterine cervixThe word stenosis refers to any passage in the body that is more narrow than it should typically be, for example a narrowed blood vessel or a narrowed spinal canal . Cervical stenosis means that the opening in the cervix is more narrow than is typical...
- Antisperm antibodies
- Non-receptive cervical mucusMucusIn vertebrates, mucus is a slippery secretion produced by, and covering, mucous membranes. Mucous fluid is typically produced from mucous cells found in mucous glands. Mucous cells secrete products that are rich in glycoproteins and water. Mucous fluid may also originate from mixed glands, which...
Diagnosis
Diagnosis of infertility begins with a medical historyMedical history
The medical history or anamnesis of a patient is information gained by a physician by asking specific questions, either of the patient or of other people who know the person and can give suitable information , with the aim of obtaining information useful in formulating a diagnosis and providing...
and physical exam. The healthcare provider may order tests, including the following:
- Lab tests
- hormone testing, to measure levels of female hormones at certain times during a menstrual cycleMenstrual cycleThe menstrual cycle is the scientific term for the physiological changes that can occur in fertile women for the purpose of sexual reproduction. This article focuses on the human menstrual cycle....
- day 2 or 3 measure of FSHFollicle-stimulating hormoneFollicle-stimulating hormone is a hormone found in humans and other animals. It is synthesized and secreted by gonadotrophs of the anterior pituitary gland. FSH regulates the development, growth, pubertal maturation, and reproductive processes of the body. FSH and Luteinizing hormone act...
and estrogenEstrogenEstrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
, to assess ovarian reserveOvarian reserveOvarian reserve is a term that is used to determine the capacity of the ovary to provide eggs that are capable of fertilization resulting in a healthy and successful pregnancy... - measurements of thyroid function (a thyroid stimulating hormone (TSH) level of between 1 and 2 is considered optimal for conception)
- measurement of progesteroneProgesteroneProgesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
in the second half of the cycle to help confirm ovulation
- hormone testing, to measure levels of female hormones at certain times during a menstrual cycle
- Examination and imaging
- an endometrial biopsyBiopsyA biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
, to verify ovulation and inspect the lining of the uterus - laparoscopyLaparoscopyLaparoscopy is an operation performed in the abdomen or pelvis through small incisions with the aid of a camera...
, which allows the provider to inspect the pelvic organs - fertiloscopy, a relatively new surgical technique used for early diagnosis (and immediate treatment)
- Pap smearPap smearThe Papanicolaou test is a screening test used in to detect pre-cancerous and cancerous processes in the endocervical canal of the female reproductive system. Changes can be treated, thus preventing cervical cancer...
, to check for signs of infection - pelvic exam, to look for abnormalities or infectionInfectionAn infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
- a postcoital test, which is done soon after intercourseSexual intercourseSexual intercourse, also known as copulation or coitus, commonly refers to the act in which a male's penis enters a female's vagina for the purposes of sexual pleasure or reproduction. The entities may be of opposite sexes, or they may be hermaphroditic, as is the case with snails...
to check for problems with sperm surviving in cervical mucous (not commonly used now because of test unreliability) - special X-rayX-rayX-radiation is a form of electromagnetic radiation. X-rays have a wavelength in the range of 0.01 to 10 nanometers, corresponding to frequencies in the range 30 petahertz to 30 exahertz and energies in the range 120 eV to 120 keV. They are shorter in wavelength than UV rays and longer than gamma...
tests
- an endometrial biopsy
There are genetic testing
Genetic testing
Genetic testing is among the newest and most sophisticated of techniques used to test for genetic disorders which involves direct examination of the DNA molecule itself. Other genetic tests include biochemical tests for such gene products as enzymes and other proteins and for microscopic...
techniques under development to detect any mutation in genes associated with female infertility.
Diagnosis and treatment of infertility should be made by physicians who are fellowship
Fellowship (medicine)
A fellowship is the period of medical training in the United States and Canada that a physician may undertake after completing a specialty training program . During this time , the physician is known as a fellow...
trained as reproductive endocrinologists. Reproductive Endocrinologists are usually Obstetrician-Gynecologists with advanced training in Reproductive Endocrinology & Infertility (in North America). These highly educated professionals and qualified physicians treat Reproductive Disorders affecting not only women but also men, children, and teens.
Prospective patients should note that reproductive endocrinology & infertility medical practices do not see women for general maternity care. The practice is primarily focused on helping their patients to conceive and to correct any issues related to recurring pregnancy loss.
Prevention
Some cases of female infertility may be prevented through identified interventions:- Maintaining a healthy lifestyle. Excessive exercise, consumption of caffeineCaffeineCaffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...
and alcoholAlcoholIn chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
, and smokingSmokingSmoking is a practice in which a substance, most commonly tobacco or cannabis, is burned and the smoke is tasted or inhaled. This is primarily practised as a route of administration for recreational drug use, as combustion releases the active substances in drugs such as nicotine and makes them...
are all associated with decreased fertility. Eating a well-balanced, nutritious diet, with plenty of fresh fruitFruitIn broad terms, a fruit is a structure of a plant that contains its seeds.The term has different meanings dependent on context. In non-technical usage, such as food preparation, fruit normally means the fleshy seed-associated structures of certain plants that are sweet and edible in the raw state,...
s and vegetableVegetableThe noun vegetable usually means an edible plant or part of a plant other than a sweet fruit or seed. This typically means the leaf, stem, or root of a plant....
s (plenty of folates), and maintaining a normal weight are associated with better fertility prospects. - Treating or preventing existing diseases. Identifying and controlling chronic diseases such as diabetes and hypothyroidismHypothyroidismHypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...
increases fertility prospects. Lifelong practice of safer sex reduces the likelihood that sexually transmitted diseaseSexually transmitted diseaseSexually transmitted disease , also known as a sexually transmitted infection or venereal disease , is an illness that has a significant probability of transmission between humans by means of human sexual behavior, including vaginal intercourse, oral sex, and anal sex...
s will impair fertility; obtaining prompt treatment for sexually transmitted diseases reduces the likelihood that such infections will do significant damage. Regular physical examinationPhysical examinationPhysical examination or clinical examination is the process by which a doctor investigates the body of a patient for signs of disease. It generally follows the taking of the medical history — an account of the symptoms as experienced by the patient...
s (including pap smearPap smearThe Papanicolaou test is a screening test used in to detect pre-cancerous and cancerous processes in the endocervical canal of the female reproductive system. Changes can be treated, thus preventing cervical cancer...
s) help detect early signs of infections or abnormalities. - Not delaying parenthood. Fertility does not ultimately cease before menopause, but it starts declining after age 27 and drops at a somewhat greater rate after age 35. Women whose biological mothers had unusual or abnormal issues related to conceiving may be at particular risk for some conditions, such as premature menopause, that can be mitigated by not delaying parenthood.