Infertility is defined as the absence of pregnancy after 1 year of regular intercourse without contraception1. Approximately 17% of couples in industrialized countries seek medical help for this reason. According to the World Health Organization, female factors lead to 37% of infertility cases and are associated with a number of diseases and conditions2,3. Let’s examine the most common of them.
Ovarian dysfunction is accounting for 25% of female infertility cases2. It can be related to various factors.
Ovulation disorders include irregular ovulation (oligoovulation) or anovulation. The WHO classification of anovulation3 is used for the detection and treatment of anovulatory disorders:
Oocyte aging is another factor of female infertility. The number and quality of oocytes decrease with age. Girls have between 1 and 2 million follicles at birth and about 300,000 follicles at the onset of puberty4. After age 35, the rate of follicle loss increases dramatically. It is accelerated by smoking, radiation, and autoimmune diseases. Women with a depleted follicle pool may ovulate regularly, but due to the poor quality of the oocytes, they cannot conceive.
The tubal factor is accounting for 11% of female infertility cases and pelvic adhesions for 12% of cases2. Both conditions inhibit normal movement of oocytes and spermatozoa through the fallopian tubes. The main causes of tubal factor infertility:
In women with obstruction of the distal Fallopian tubes, hydrosalpinx may develop – the accumulation of fluid in the lumen of the tube. It reduces the success rate of in vitro fertilization. Hydrosalpinx prevents the migration of spermatozoa, and also leads to the reverse reflux of the contents of the fallopian tubes into the endometrial cavity, which creates a hostile environment for embryo implantation5.
The main cause of uterus infertility is a disruption of the embryo implantation. Uterine fibroids (leiomyoma) are common benign tumors of smooth muscles. Fibroids with submucosal and intracavitary components may reduce pregnancy rates and implantation. Doctors consider hormonal changes in hypothalamus-pituitary-ovaries-uterus system to be the main factor in reproductive dysfunction in uterine fibroids. Many patients with fibroids have anovulatory cycles with varying levels of estrogen saturation or biphasic cycles with luteal phase deficiency. Mechanical factors also play a certain role. For example, if the tumor is located in the region of the tubal angle, it compresses the interstitial part of the tube and interferes with its patency. Surgical removal of the tumor increases likelihood of the implantation6.
Congenital uterine anomalies are important causes of infertility and miscarriage. A unicornuate uterus is formed when the growth of one Müllerian duct stops or slows down and the other develops normally. With such an anomaly pregnancy is possible, but its outcome depends on uterus size. The bicornuate uterus is formed by incomplete fusion of the middle part of the Müllerian ducts. It has two cavities and one cervix, less often two, which are connected to a normal vagina or a vagina separated by a partial septum. Two halves in the uterus, separated by a rebirth, are associated with the worst reproductive outcome7.
Endometrial polyps and synechiae also lead to female infertility. The causes of synechia are:
Endometriosis is one of the most common pathologies of the reproductive age. While healthy women have a 15–20% chance of becoming pregnant in any single menstrual cycle, untreated women with genital endometriosis have a 2–10% chance8,9. Endometriosis is responsible for 15% of female infertility2. This is a multifactorial disease in which a benign growth of endometrium tissue occurs above its normal location.
Current theories do not fully reveal the true etiology of infertility associated with endometriosis. But there are insights about tubal factor, ovarian dysfunction, changes in endometrial receptivity, and others. A special place is given to resistance to progesterone, which is associated with a decrease in the total number of progesterone receptors. This pathology impairs the expression of progesterone-inducible proteins important for endometrial implantation and receptivity8,9.
Cervical factors. Normal cervical mucus facilitates the transport of sperm in the middle of the cycle. With congenital malformations and cervix injuries, including surgical ones, stenosis and inability of the cervix to produce normal mucus may occur. This will reduce fertility.
Immune factors. Women with certain autoimmune diseases have an increased risk of infertility unrelated to the direct effects of antibodies on fertilization and implantation. For example, premature ovarian failure has been described in women with systemic lupus erythematosus and myasthenia gravis. Autoimmune oophoritis can occur as a part of the polyglandular autoimmune deficiency syndrome type I and type II. Patients with untreated celiac disease may also have an increased incidence of reproductive disorders, including infertility, miscarriage, and intrauterine growth restriction10.
Genetic causes. It has been shown that infertile couples have a higher prevalence of karyotype anomalies (trisomy, mosaic, translocation) than the general population11. Frequency varies depending on the cause of infertility and medical history. The scientists also identified individual genes that affect fertility, including KAL1, the FSH receptor, TUBB8. Mutations of the latter are unique in that they affect only oocytes, disrupting the function of microtubules during oocyte division and stopping their maturation12.
Unexplained infertility is a diagnosis of exclusion. Many cases of unexplained infertility can be associated with a slight influence of several factors at once.
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