Female infertility


Female infertility refers to infertility in women, which is the inability to conceive after sexual intercourse. It affects an estimated 48 million women, globally.
Female infertility varies widely by region, The highest rates of female infertility are found in Eastern Europe and South Central Asia, followed by South Asia, Sub-Saharan Africa, and Middle East and North Africa. Female infertility rates are lowest in East Asia and Latin America.
Fertility is affected by a variety of factors, including hormones, nutritional status, disease, and malformations of the uterus. Infertility affects women from around the world, and the social stigmas affecting infertile women may vary from region to region.

Cause

Causes or factors of female infertility can basically be classified regarding whether they are acquired or genetic disorder, or strictly by location.
Although factors of female infertility can be classified as either acquired or genetic, female infertility is usually more or less a combination of nature and nurture. Also, the presence of any single risk factor of female infertility does not necessarily cause infertility, and even if a woman is definitely infertile, the infertility cannot definitely be blamed on any single risk factor even if the risk factor is present.

Hormonal dysfunction

Ovulatory hormonal disorders are the greatest single contributing factor to female infertility. Anovulation, or the failure to ovulate, is primarily caused by insufficient hormone levels, including low estrogen levels, insufficient GnRH secretion, as well as insufficient levels of other hormones secreted by the hypothalamus and pituitary glands. However, women with normal estrogen levels can also suffer from low fertility, such as in the case of women with PCOS.
It is not understood why women with PCOS and normal estrogen levels can still be infertile. However, it is believed that imbalanced secretion of GnRH can explain why such women fail to conceive, highlighting the need for hormonal balance in women with PCOS.

Acquired

According to the American Society for Reproductive Medicine, 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, which may present as infertility many years later as an adult.

Age

A woman's fertility is affected by her age. The average age of a girl's first period is 12–13, but, in postmenarchal girls, about 80% of the cycles are anovulatory in the first year after menarche, 50% in the third and 10% in the sixth year. A woman's fertility peaks in the early and mid 20s, after which it starts to decline, with this decline being accelerated after age 35. However, the exact estimates of a woman's chances 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, including the general health of a woman and the fertility of the male partner.
Menopause typically occurs between 44 and 58 years of age. DNA testing is rarely carried out to confirm claims of maternity at advanced ages, but in one large study, among 12,549 African and Middle Eastern immigrant mothers, confirmed by DNA testing, only two mothers were found to be older than fifty, the oldest mother being 52.1 years at conception.

Tobacco smoking

is harmful to the ovaries, and the degree of damage is dependent upon the amount and length of time a woman smokes or is exposed to a smoke-filled environment. Nicotine and other harmful chemicals in cigarettes interfere with the body's ability to create estrogen, a hormone that regulates folliculogenesis and ovulation. 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 by approximately 1–4 years.

Sexually transmitted infections

s 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 or overweight. Fat cells produce estrogen, in addition to the primary sex organs. 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. 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 1,000 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.

Radiation

Exposure to radiation poses a high risk of infertility, depending on the frequency, power, and exposure duration. Radiotherapy is reported to cause infertility.

Chemotherapy

poses a high risk of infertility. 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 bleomycin and dactinomycin and antimetabolites such as methotrexate, mercaptopurine and 5-fluorouracil.
Female infertility by chemotherapy appears to be secondary to premature ovarian failure by loss of primordial follicles. This loss is not necessarily a direct effect of the chemotherapeutic agents, but could be due to an increased rate of growth initiation to replace damaged developing follicles. Antral follicle count decreases after three series of chemotherapy, whereas follicle stimulating hormone reaches menopausal levels after four series. Other hormonal changes in chemotherapy include decrease in inhibin B and anti-Müllerian hormone levels.
Women may choose between several methods of fertility preservation prior to chemotherapy, including cryopreservation of ovarian tissue, oocytes or embryos.

Immune infertility

have been considered as infertility cause in around 10–30% of infertile couples. ASA production are directed against surface antigens on sperm, which can interfere with sperm motility and transport through the female reproductive tract, inhibiting capacitation and acrosome reaction, impaired fertilization, influence on the implantation process, and impaired growth and development of the embryo. Factors contributing to the formation of antisperm antibodies in women are disturbance of normal immunoregulatory mechanisms, infection, violation of the integrity of the mucous membranes, rape and unprotected oral or anal sex.

Other acquired factors

  • Adhesions secondary to surgery in the peritoneal cavity is the leading cause of acquired infertility. A meta-analysis in 2012 came to the conclusion that there is only little evidence for the surgical principle that using less invasive techniques, introducing less foreign bodies or causing less ischemia reduces the extent and severity of adhesions.
  • Diabetes mellitus. A review of type 1 diabetes came to the result that, despite modern treatment, women with diabetes are at increased risk of female infertility, such as reflected by delayed puberty and menarche, menstrual irregularities, mild hyperandrogenism, polycystic ovarian syndrome, fewer live born children and possibly earlier menopause. Animal models indicate that abnormalities on the molecular level caused by diabetes include defective leptin, insulin and kisspeptin signalling.
  • Coeliac disease. Non-gastrointestinal symptoms of coeliac disease may include disorders of fertility, such as delayed menarche, amenorrea, infertility or early menopause; and pregnancy complications, such as intrauterine growth restriction, small for gestational age babies, recurrent abortions, preterm deliveries or low birth weight babies. Nevertheless, gluten-free diet reduces the risk. Some authors suggest that physicians should investigate the presence of undiagnosed coeliac disease in women with unexplained infertility, recurrent miscarriage or IUGR.
  • Significant liver or kidney disease
  • Thrombophilia
  • Cannabis smoking, such as of marijuana causes disturbances in the endocannabinoid system, potentially causing infertility
  • Radiation, such as in radiation therapy. The radiation dose to the ovaries that generally causes permanent female infertility is 20.3 Gy at birth, 18.4 Gy at 10 years, 16.5 Gy at 20 years and 14.3 Gy at 30 years. After total body irradiation, recovery of gonadal function occurs in 10−14% of cases, and the number of pregnancies observed after hematopoietic stem cell transplantation involving such as procedure is lower than 2%.