Infertility is called a failure to conceive (regardless of cause) after one year of unprotected intercourse. This condition affects approximately 10 to 15% of reproductive-aged couples. Both males and females contribute to the problem but we will focus on issues faced by women.
Factors that affect female fertility
Female factors that affect fertility include the following categories:
- Cervical: Narrowing of the openings or abnormalities of the mucus-sperm interaction.
- Uterine: Congenital or acquired defects; may affect endometrium or myometrium; scarring from infections or dilation and curettage (D&C), may lead to pregnancy wastage and premature delivery.
- Ovarian: Alteration in the frequency and duration of the menstrual cycle primarily due to lack of ovulation; seen commonly in polycystic ovarian syndrome (PCOS).
- Tubal: Abnormalities or damage to the fallopian tube; pelvic inflammatory disease from sexually transmitted infections or scar tissue from endometriosis.
- Peritoneal (lining of the pelvis): Anatomic defects or infection, adhesions, adnexal masses.
Cervical factor infertility
Cervical factor infertility can be caused by narrowing or abnormalities of the mucus-sperm interaction. The uterine cervix allows for the transport and activation of the sperm after intercourse. Cervical factors account for 5 to 10% of infertility. Cervical mucus production and characteristics change according to the estrogen and progesterone concentration during the period right before menses.
Characteristics of mucus:
- Early in the cycle, right after menses, the cervical mucus is scanty, and thick that does not allow the passage of sperm. Mucus secretion increases right before ovulation.
- The mucus becomes thin, watery, alkaline, acellular, and elastic because if the increased concentration of sodium chloride.
- Mucus acts as a filter for abnormal sperm and cellular debris present in the semen.
- Mucus secretion may be altered by hormonal changes and medications, especially drugs like clomiphene citrate, which decrease the production.
- Hypoestrogenism may cause thickened cervical mucus, which impairs the passage of sperm.
- Cervical stenosis can cause infertility by blocking the sperm so it cannot access the uterine cavity and fallopian tube. Cervical stenosis can be due to surgical procedures, infections, hypoestrogenism, and radiation therapy.
Uterine factor infertility
The uterus is the final destination for the embryo after it is fertilized in the fallopian tube and the place where the fetus develops until delivery. They can cause pregnancy wastage and premature delivery. Uterine factors can be congenital or acquired and are responsible for 2 to 5% of infertility cases.
The full spectrum of congenital uterine abnormalities varies from total absence of the uterus and vagina (Rokitansky-Küster-Hauser syndrome) to minor defects such as misshaped uterus and vaginal septa (transverse or longitudinal).
The most common uterine malformations observed in the past 40 years were drug induced as a result of diethylstilbestrol (DES) use that was used to treat patients with a history of recurrent miscarriages. Years later, DES was found to be responsible for inducing malformations of the uterine cervix, irregularities of the endometrial cavity, malfunction of the fallopian tubes, menstrual irregularities, and the development of clear cell carcinoma of the vagina.
Premature delivery has been associated with cervical incompetence, unicornuate uterus (incomplete and formation and smaller cavity), and septate uterus. Septate uterus can cause implantation problems and first-trimester miscarriages.
Endometritis is an infection of the lining of the uterus and is associated with a traumatic delivery, Cesarean section, dilation and curettage, intrauterine device, or any surgery or procedure of the endometrial cavity. This may create intrauterine adhesions with partial or total blockage of the endometrial cavity.
Placental polyps may develop and block implantation sometimes due to placental remains.
Intrauterine and submucosal fibroids are very common, affecting 25 to 50% of women and can cause distortion of the cavity and limit the blood supply. They may also be implicated in implantation failure, early miscarriages, premature delivery, and placental abruption (which occurs when the placental pulls away from the uterine wall).
Ovarian factor infertility
At birth, the number of eggs in the ovaries is reduced to approximately two million. By menarche, approximately 500,000 eggs or oocytes are present.
The ovulatory process is initiated by the hypothalamus-pituitary-ovarian axis. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH), under the regulation of gonadotropin-releasing hormone (GnRH), cause an egg to be released and the estrogen and progesterone are released from the ovaries to prime the lining for implantation of the embryo. Estrogen generates the LH surge that triggers the ovulatory process and stimulates the formation of the corpus luteum and subsequent progesterone secretion.
Ovulatory dysfunction or failure to ovulate is the most common infertility problem. Absence of ovulation can be associated with primary amenorrhea, secondary amenorrhea, or oligomenorrhea. Amenorrhea means the absence of menses.
Primary amenorrhea is the absence of a spontaneous menstrual period by age 16 years or after three years of pubarche and the larch.
- Hypergonadotropic hypogonadism is often related to ovarian development failure, as in Turner syndrome, where the karyotype 45,X indicates an absence of an X chromosome. Drugs for chemotherapy and radiation can cause hypergonadotropic hypogonadism.
- Hypogonadotropic hypogonadism is due to hypothalamic failure due to inadequate GnRH synthesis, neurotransmitter defects, or isolated gonadotropin insufficiency. Chronic disease conditions, high levels of stress, and starvation or malnutrition are other possible causes.
Anatomic or structural problems associated with primary amenorrhea include congenital absence of the uterus, vagina, or hymen (cryptomenorrhea).
Secondary amenorrhea is the absence of menses for more than six months in a woman who has previously menstruated. Pregnancy should always be ruled out first.
In the absence of pregnancy, this condition is likely due to abnormalities of the thyroid, adrenal, and pituitary, including tumors.
One common cause of secondary amenorrhea is premature ovarian failure, which is the loss of ovarian function by the age of 40.
Oligomenorrhea causes irregular menstrual cycles that can be separated by 35 days to five months, and sometimes is associated with a history of dysfunctional uterine bleeding or prolonged periods of breakthrough bleeding.
Patients may have symptoms of excess androgen like testosterone, which causes acne, hirsutism, and baldness. Obesity is frequently seen and usually the condition is called Polycystic Ovarian Syndrome (PCOS). Their fertility is decreased.
Advanced age. The prevalence of infertility rises dramatically as age increases. Ovulatory problems and poor egg quality are the biggest factors.
The fallopian tubes pick up the egg from the ovary where the sperm fertilizes it. The fertilized egg travels to the uterus where it implants approximately 96 to 120 hours after ovulation.
Abnormalities or damage to the fallopian tube interferes with fertility and is responsible for abnormal implantation such as an ectopic pregnancy.
Other tubal factors associated with infertility are either congenital or acquired. Elective tubal ligation (sterilization) and removal of the tubes are acquired causes.
The uterus, ovaries, and fallopian tubes share the same space within the peritoneal cavity. Anatomical defects or dysfunctions of the peritoneal cavity, including infection, adhesions, and adnexal masses, may cause infertility.
Pelvic inflammatory disease, scar tissue or adhesions from previous pelvic surgery, endometriosis, and ovarian cyst rupture all compromise the motility of the fallopian tubes or cause blockage. Large myomas (fibroids) and pelvic masses can block the tubes.
Pelvic inflammatory disease
Pelvic inflammatory disease (PID) has been associated with gonorrhea and chlamydia infection. It causes scarring and blockage. One study reported a 21% incidence of infertility in a group of Swedish women who were diagnosed with PID.
The rate of damage to the fallopian tubes increases with repeated infections, from 34% after the first episode to 54% in women with second and third episodes.
Endometriosis remains a complicated and poorly understood disease that affects women during their reproductive years. The disease progression is unpredictable. Pelvic pain and infertility are the two major complaints of patients with endometriosis.
There is a genetic link based on the finding of chromosomal defects in endometriotic tissue and a seven-fold increased risk of endometriosis in patients with a family history of it.
Endometriotic lesions vary and the classic finding is a nodule that appears as bluish-black pigments, (ie. "powder-burn lesions") that affect the peritoneal surfaces of the bladder, ovary, fallopian tubes, cul-de-sac, and bowel. Non-classic endometriosis may appear as red, tan, or white lesions and vesicles.
Minimal and mild endometriosis may reduce fertility by the following mechanisms:
- Increased peritoneal macrophages (white blood cells) that increase the sperm.
- Decreased sperm binding to the egg.
- Immune dysfunction.
- Increase in inflammatory mediators.
- Serum that is toxic to the embryo.
Endometriosis has been associated with ovulatory disorders such as luteal phase deficiency (LPD), reduced ovulation, and persistent ovarian cysts.
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