Female Infertility: Definition, Prevalence, Causes, Factors, Diagnosis, Treatment and Prevention

Refers to sterility in human women or inability to get pregnant.

It affects approximately 48 million women. The highest prevalence of infertility afflicts people in South Asia, Sub-Saharan Africa, North Africa / Middle East, Central / Eastern Europe, and Central Asia.

Infertility is caused by many sources, including nutrition, disease, and other malformations of the uterus. Infertility affects women around the world, and the cultural and social stigma surrounding it varies.

Definition

There is no unanimous definition of female infertility, because the definition depends on social and physical characteristics that can vary by culture and situation. The guidelines of the National Institute for Excellence in Health and Care state that:

“A woman of reproductive age who has not conceived after one year of unprotected vaginal intercourse, in the absence of a known cause of infertility, should be offered additional clinical evaluation and investigation with her partner.”

Consultation with a fertility specialist sooner is recommended if the woman is 36 years of age or older, or if there is a known clinical cause of infertility or a history of predisposing factors for infertility.

According to the World Health Organization (WHO), infertility can be described as the inability to become pregnant, maintain a pregnancy, or carry a pregnancy to a live birth.

A clinical definition of infertility by the World Health Organization and the International Assisted Reproductive Technologies Monitoring Committee is:

“A disease of the reproductive system defined by the inability to achieve a clinical pregnancy after 12 months or more of regular unprotected intercourse.”

Infertility can be divided into primary and secondary infertility. Primary infertility refers to the inability to give birth either because you cannot get pregnant, or because of carrying a child to a live birth, which can include a miscarriage or stillbirth.

Secondary infertility refers to the inability to conceive or give birth when there was a previous pregnancy or live birth.

Predominance

Female infertility varies widely based on geographic location around the world. In 2010, there were approximately 48.5 million infertile couples worldwide, and from 1990 to 2010 there was little change in infertility levels in most parts of the world.

In 2010, the countries with the lowest rates of female infertility were the South American countries of Peru, Ecuador, and Bolivia, as well as Poland, Kenya, and the Republic of Korea. The regions with the highest rates include Eastern Europe, North Africa, the Middle East, Oceania, and Sub-Saharan Africa.

The prevalence of primary infertility has increased since 1990, but secondary infertility has generally decreased. Rates (though not prevalence) of female infertility decreased in high-income regions, Central and Eastern Europe, and Central Asia.

Africa

Sub-Saharan Africa has had declining levels of primary infertility from 1990 to 2010.

Within the sub-Saharan region, rates were lowest in Kenya, Zimbabwe, and Rwanda, while rates were highest in Guinea, Mozambique, Angola, Gabon, and Cameroon, along with North Africa near the Middle East.

According to a 2004 Department of Homeland Security report, rates in Africa were highest in Central and Sub-Saharan Africa, with rates in East Africa very close.

Asia

In Asia, the highest rates of combined secondary and primary infertility were recorded in the South Central region, and then in the Southeast region, with the lowest rates in the western areas.

Latin america and the caribbean

The prevalence of female infertility in the Latin America / Caribbean region is typically lower than the global prevalence. However, the highest rates were recorded in Jamaica, Suriname, Haiti, and Trinidad and Tobago.

Central and Western America have some of the lowest prevalence rates. The highest regions of Latin America and the Caribbean were found in the Caribbean islands and in the least developed countries.

Causes and factors

The causes or factors of female infertility can be basically classified with respect to whether they are acquired or genetic, or strictly by location.

Although female infertility factors can be classified as acquired or genetic, female infertility is generally more or less a combination of nature and nutrition.

Also, the presence of any individual risk factors for female infertility (such as smoking, mentioned below) does not necessarily cause infertility, and even if a woman is definitely infertile.

Infertility definitely cannot be attributed to any 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 affect fertility.

In a broad sense, acquired factors include virtually any factor that is not based on a genetic mutation, including any intrauterine exposure to toxins during fetal development, which can present as infertility many years later as an adult.

Ages

A woman’s fertility is affected by her age. The average age of a girl’s first period is 12-13 years (12.5 years in the United States, 12.72 in Canada, 12.9 in the United Kingdom).

But, in post-menarchal girls, about 80% of 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 to mid-20s, after which it begins to decline, and this decline accelerates after age 35.

However, the exact estimates of the chances that a woman will conceive after a certain age are not clear giving different results.

A couple’s chances of successfully conceiving later in life depend on many factors, including the overall health of a woman and the fertility of the male partner.

Smoking

Smoking tobacco is harmful to the ovaries, and the degree of damage depends on the amount and how long a woman smokes or is exposed to a smoky environment.

Nicotine and other harmful chemicals in cigarettes interfere with the body’s ability to create estrogen, a hormone that regulates folliculogenesis and ovulation.

Additionally, cigarette smoking interferes with folliculogenesis, embryo transport, endometrial receptivity, endometrial angiogenesis, uterine blood flow, and uterine myometrium.

Some damage is irreversible, but quitting smoking can prevent further damage. Smoking reduces the chances that IVF will produce a live birth by 34% and increases the risk of IVF during pregnancy by 30%.

Also, smokers have an earlier onset of menopause in about 1-4 years.

Sexually transmitted infections

Sexually transmitted infections are the leading cause of infertility. They often show few if any visible symptoms, at the risk of not seeking appropriate treatment in time to avoid decreased fertility.

Body weight and eating disorders

Twelve percent of all infertility cases are the result of an underweight or overweight woman. Fat cells produce estrogen in addition to the primary sex organs.

Too much body fat causes the production of too much estrogen and the body begins to react as if it were on birth control, limiting the chances of getting pregnant. Too little body fat causes insufficient estrogen production and the disruption of the menstrual cycle.

Overweight and non-overweight women have irregular cycles in which ovulation does not occur or is inadequate. Proper nutrition in the first years of life is also an important factor for later fertility.

A study in the USA indicated that approximately 20% of infertile women had a past or present eating disorder, which is five times the overall lifetime prevalence rate.

A 2010 review concluded that overweight and obese subfertile women have a reduced chance 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 birth in overweight and obese anovulatory women was, respectively, 54 and 100% higher than their normal weight counterparts, for ovulatory women they were 44 and 70% higher, respectively.

Chemotherapy

Chemotherapy poses a high risk of infertility. The antral follicle count declines after three rounds of chemotherapy, while follicle-stimulating hormone (FSH) reaches menopausal levels after four rounds.

Other hormonal changes in chemotherapy include decreased inhibin B and anti-Müllerian hormone levels.

Immune infertility

Antisperm antibodies (ASA) have been considered causes of infertility in about 10-30% of infertile couples.

The production of antisperm antibodies is directed against surface antigens on sperm, which can interfere with the motility and transport of sperm through the female reproductive tract.

Inhibiting acrosomal training and reaction, impaired fertilization, influence on the implantation process and the growth and development of the embryo.

Factors that contribute to the formation of antisperm antibodies in women are disruption of normal immunoregulatory mechanisms, infection, violation of the integrity of the mucous membranes, accidental rape, and unprotected oral or anal sex.

Other acquired factors

Adhesions secondary to surgery in the peritoneal cavity are the main cause of acquired infertility.

A meta-analysis conducted in 2012 concluded that there is very little evidence for the surgical principle that using less invasive techniques, introducing fewer foreign bodies, or reducing ischemia reduces the extent and severity of adhesions.

Diabetes mellitus : A review of type 1 diabetes found that, despite modern treatment, women with diabetes are at increased risk of female infertility.

As reflected by delayed puberty and menarche, menstrual irregularities (especially oligomenorrhea), mild hyperandrogenism, polycystic ovary syndrome, fewer live-born children, and possibly earlier menopause.

Animal models indicate that abnormalities at the molecular level caused by diabetes include defective leptin, insulin, and kisspeptin signaling.

Celiac disease : Non-gastrointestinal symptoms of celiac disease can include fertility disorders, such as delayed menarche, amenorrhea, infertility, or early menopause.

And pregnancy complications, such as intrauterine growth restriction (IUGR), small-for-gestational age (SGA) babies, recurrent miscarriages, premature delivery, or low-birth-weight babies ( LBW).

However, the gluten-free diet reduces the risk. Some authors suggest that clinicians should investigate the presence of undiagnosed celiac disease in women with unexplained infertility, recurrent miscarriage, or intrauterine growth restriction.

Cannabis use, like marijuana, causes disturbances in the endocannabinoid system, which can cause infertility.

Radiation, 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 age 30.

After total body irradiation, recovery of gonadal function occurs in 10-14% of cases, and the number of pregnancies seen after hematopoietic stem cell transplantation involving such a procedure is less than 2% .

Genetic factors: There are many genes in which the mutation causes female infertility, as shown in the table below.

Additionally, there are additional conditions involving female infertility that are believed to be genetic, but where no responsible gene has been found, especially 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 can manifest as frank infertility.

Chromosomal abnormalities that cause female infertility include Turner syndrome. Some of these gene or chromosomal abnormalities cause intersex conditions, such as androgen insensitivity syndrome .

Diagnosis

The healthcare provider may order tests, including the following:

Lab tests

  • Hormone tests, to measure female hormone levels at certain times during a menstrual cycle.
  • Day 2 or 3 measurement of follicular stimulating hormone and estrogen, to evaluate the ovarian reserve.
  • Anti-Müllerian hormone to estimate ovarian reserve.

Imaging exams

  • An endometrial biopsy to check ovulation and inspect the lining of the uterus.
  • Laparoscopy , which allows the doctor to inspect the pelvic organs.
  • Pap smear, to look for signs of infection.
  • Hysterosalpingography or sonosalpingography, to verify the patency of the tube.
  • Sonohisterography to detect uterine abnormalities.

Genetic testing techniques are under development to detect any mutation in the genes associated with female infertility.

Treatment

Initial diagnosis and treatment of infertility is usually done by OB / GYNs or nurses. If initial treatments are unsuccessful, referral is generally made to physicians who have fellowship training as reproductive endocrinologists.

Reproductive endocrinologists are generally OB / GYNs with advanced training in reproductive endocrinology and infertility (in North America).

These doctors treat reproductive disorders that affect not only women but also men, children, and adolescents.

In general, reproductive endocrinology and infertility medical practices do not consider women for general maternity care.

Prevention

Acquired female infertility can be prevented through identified interventions:

Maintain a healthy lifestyle : Excessive exercise, caffeine, alcohol, and smoking have been associated with decreased fertility.

Eating a balanced and nutritious diet, with plenty of fresh fruits and vegetables, and maintaining a normal weight, on the other hand, have been associated with better fertility prospects.

Freezing Eggs: A woman can freeze her eggs and preserve her fertility.

By using egg freezing during peak reproductive years, a woman’s oocytes are cryogenically frozen and ready for use later in life, reducing her chances of female infertility.

Society and culture

Social stigma

The social stigma due to infertility is seen in many cultures around the world in various forms. Often times when women are unable to conceive, they are blamed, even when about 50% of infertility problems come from men.

Furthermore, many societies only tend to value a woman if she is capable of producing at least one child, and a marriage can be considered a failure when the couple cannot conceive.

The act of conceiving a child can be linked to the consummation of the couple’s marriage and reflect their social role in society.

This is seen in the ‘African infertility belt’, where infertility is prevalent in Africa, including countries ranging from Tanzania in the east to Gabon in the west. In this region, infertility is highly stigmatized and can be considered a failure of the couple in their societies.

This is demonstrated in Uganda and Nigeria, where there is great pressure on pregnancy and its social implications. This is also seen in some Muslim societies, including Egypt and Pakistan.

Wealth is sometimes measured by the number of children a woman has, as well as the inheritance of property. Children can influence financial security in many ways. In Nigeria and Cameroon, land claims are decided by the number of children.

Furthermore, in some sub-Saharan countries, women may be denied inheritance if they did not have children. In some African and Asian countries, a husband may deprive his infertile wife of food, shelter, and other basic necessities such as clothing.

In Cameroon, a woman can lose access to land at the hands of her husband and be left alone in old age. In many cases, a woman who cannot have children is excluded from social and cultural events, including traditional ceremonies.

This stigmatization is seen in Mozambique and Nigeria, where infertile women have been treated as outcasts to society. This is a humiliating practice that devalues ​​infertile women in society.

In the Macua tradition, pregnancy and birth are considered important events in a woman’s life, with the ceremonies of nthaa’ra and ntha’ara no mwana, which can only be attended by women who have been pregnant and have had a baby.

The effect of infertility can lead to social shame of the internal and social norms surrounding pregnancy, which affects women around the world.

When pregnancy is seen as such an important life event and considered a “socially unacceptable condition,” it can lead to a search for treatment in the form of traditional healers and expensive Western treatments.

Limited access to treatment in many areas can lead to extreme and sometimes illegal acts to produce a child.

Marital role

Men in some countries can find another wife when the first cannot have a child, hoping that by sleeping with more women she can have her own child.

This can be prevalent in some societies, such as Cameroon, Nigeria, Mozambique, Egypt, Botswana, and Bangladesh, among many more, where polygamy is more common and more socially acceptable.

In some cultures, including Botswana and Nigeria, women can choose a woman with whom they allow their husband to sleep in hopes of conceiving a child.

Women who are desperate for children can commit to their husband to select a woman and accept the duties of caring for children so that they feel accepted and useful in society.

Women can also sleep with other men in hopes of getting pregnant. This can be done for many reasons, including advice from a traditional healer, or finding out if another man was “more compatible.”

In many cases, the husband was unaware of the additional sexual intercourse and would not be informed if a woman became pregnant by another man.

However, this is not culturally acceptable and can contribute to the gender suffering of women who have fewer options to become pregnant on their own than men.

Men and women can also resort to divorce to try to find a new partner with whom to have a child.

Infertility in many cultures is a reason for divorce, and a way for a man or woman to increase their chances of producing an heir.

When a woman is divorced, she can lose her security that often comes with land, wealth, and a family. This can ruin marriages and can lead to mistrust in the marriage.

Increased sexual partners can potentially result in the spread of disease, including HIV / AIDS , and may actually contribute to future generations of infertility.