Causes of Infertility in Women

What is Female Infertility?

Infertility is defined as the inability to conceive after one year of regular, unprotected sexual intercourse. If the woman is over the age of 35, this period is reduced to six months.

What Causes Female Infertility?

Female-related problems account for approximately 40–45% of infertility cases. Common causes include:

• Ovulation disorders
• Damaged or blocked fallopian tubes
• Endometriosis
• Cervical problems
• Congenital abnormalities of the uterus or absence of the uterus or vagina
• Uterine fibroids, uterine polyps, uterine anomalies, tumors outside the uterus
• Allergic causes
• Pelvic infections
• Hormonal imbalances – such as elevated prolactin levels or excess male hormones
• Thyroid disorders
• Certain genetic conditions
• Being overweight
• Polycystic ovary syndrome (PCOS)
• Previous cancer treatments such as radiotherapy or chemotherapy
• Diminished ovarian reserve
• Premature menopause

What Are the Symptoms of Female Infertility?

• Irregular menstrual cycles
• Absence of menstruation
• Excessive or scanty menstrual bleeding
• Bleeding between periods
• Back pain, pelvic pain, or cramping
• Painful menstruation

Sometimes female infertility is related to hormonal issues. In such cases, symptoms may include:

• Acne
• Changes in sexual desire
• Hair growth on the upper lip, chest, or chin
• Hair thinning or hair loss
• Weight gain

Other symptoms that may indicate conditions linked to infertility include:

• Milky discharge from the nipples unrelated to breastfeeding
• Pain during sexual intercourse

Many other factors can contribute to female infertility, and symptoms may vary widely.

How Is Female Infertility Diagnosed?

In couples seeking help due to difficulty conceiving, the evaluation of possible causes of female infertility involves:

• The woman's age
• Duration of attempting to conceive and results of any prior evaluations or treatments
• Menstrual cycle history (regular cycles, ovulation pain, breast tenderness, or mid-cycle spotting suggest ovulation; painful periods may indicate endometriosis)
• Medical, surgical, and gynecological history (history of sexually transmitted infections, pelvic inflammatory disease, treatment for abnormal Pap smears, or abdominal surgeries). During the review of systems, patients should be questioned about thyroid disorders, nipple discharge, excessive hair growth, pelvic or lower abdominal pain, menstrual cramps, and pain during intercourse
• Pregnancy history (previous pregnancies, births, outcomes, and any related complications)
• Sexual history (frequency of intercourse, sexual dysfunctions)
• Family history (infertility in the family, early menopause, birth defects, genetic disorders, intellectual disabilities)
• Lifestyle factors (occupation, exercise, stress, weight changes, smoking, and alcohol use)

Weight and Body Mass Index (BMI):

Increased BMI is associated with reduced fertility. Abdominal obesity is linked to insulin resistance.

Development of Secondary Sexual Characteristics and Body Type:

In hypogonadotropic hypogonadism, secondary sexual characteristics may be underdeveloped. In Turner syndrome, short stature and webbed neck may be observed.

Thyroid Disorders:

Thyroid nodules, tenderness, or abnormal size, along with symptoms such as nipple discharge, hirsutism, and acne, may indicate endocrine disorders. These symptoms require further evaluation for adrenal disorders, polycystic ovary syndrome (PCOS),elevated prolactin, and hyper- or hypothyroidism.

Pelvic Examination:

Pelvic tenderness may suggest chronic pelvic pain or endometriosis. Structural abnormalities of the vagina and cervix, abnormal discharge, and congenital anomalies of the uterus and tubes, as well as infections or cervical factors, should also be assessed.

An abnormally sized uterus, irregular uterine structure, or fixed position may point to uterine anomalies, endometriosis, or pelvic adhesions.

How to Detect Infertility in Single Women?

Single women may also exhibit symptoms suggestive of infertility similar to married women. If a single woman experiences any of these symptoms, she should consult a doctor and undergo ultrasound examinations and relevant tests.

What Tests Are Done to Investigate Female Infertility?

Evaluation of Ovulation

• Serum Progesterone Measurement: Serum progesterone levels reach their highest point 7-8 days after ovulation. In a 28-day menstrual cycle, a serum progesterone level greater than 3 ng/mL on day 21 supports ovulation, but it does not provide information about the quality of the luteal phase. Progesterone levels greater than 10 ng/mL on day 21 of a normal cycle indicate healthy and normal ovulation.
• Urinary Ovulation Tests: Home urine LH test kits can be used to track ovulation and provide information about the timing of ovulation. Usually, testing starts on day 10 of the menstrual cycle, and the urine is checked in the evening when it is not too diluted or concentrated. Ovulation is expected to occur 24-48 hours after a color change is detected. However, home tests have a 5-10% false positive and negative rate.
• Serial Ultrasound to Track Ovulation: Although it is highly reliable, this test is expensive and more labor-intensive compared to others.

Evaluation of Fallopian Tubes

Hysterosalpingography (HSG): This test, also known as an X-ray of the uterus and fallopian tubes, is commonly used to examine the structural and functional characteristics of the cervix, uterus, and fallopian tubes. A contrast material is introduced into the uterine cavity, and its passage through the tubes and subsequent distribution into the abdominal cavity provides information about the tubes. It also detects congenital anomalies and pathologies of the uterine lining (polyps, fibroids, intrauterine adhesions). HSG should be performed 1-2 days after the end of menstruation. It provides accurate information 65-85% of the time but does not reveal adhesions around the tubes or endometriosis. Older HSG images (over 2 years) should be repeated. HSG can also have a therapeutic role. Blocked tubes can sometimes be opened by the pressure of the contrast material during the procedure. Abnormal HSG findings may require further evaluation with hysteroscopy or laparoscopy.

Before performing HSG, a complete gynecological evaluation is conducted. If signs of pelvic infection are present, the procedure is postponed until the infection is treated. Performing HSG during infection can spread the disease. HSG is generally tolerable with minimal pain and is typically not performed under general anesthesia.

Chlamydia Ig G Antibodies: This painless, cost-effective, and easy test provides information about the presence of damage to the tubes. Many recent studies have shown that chlamydia infections can cause damage to the fallopian tubes, leading to infertility, even without pelvic inflammatory disease. Major infertility guidelines (such as those by the RCOG) recommend testing for chlamydia antibodies in all women before HSG or any invasive procedure in the uterus.

Evaluation of Uterine Lining

• Hysterosonography: This test involves injecting saline into the uterine lining under ultrasound guidance to diagnose polyps, fibroids, adhesions, and congenital abnormalities of the uterus.
• Hysteroscopy: This involves examining the uterus and the openings of the fallopian tubes inside the uterus using a special optical camera. It is both a diagnostic and a therapeutic procedure. The camera is inserted through the cervix, and images are displayed on a monitor. Surgical procedures can also be performed with specialized instruments at the tip of the hysteroscope. Hysteroscopy is usually done under general anesthesia in an operating room, and patients can typically go home on the same day after the procedure.
• Laparoscopy: The role of laparoscopy in infertility evaluation is debated. It is an expensive test that requires surgery. Laparoscopy may be indicated when endometriosis is suspected (painful periods, pelvic pain, deep pain during intercourse),in cases with a history of pelvic adhesions or tube-related diseases (pelvic pain, complicated appendicitis, pelvic infection, pelvic surgery, previous ectopic pregnancy),abnormal physical examination findings, or when HSG results are normal. In cases of unexplained or male-factor infertility, laparoscopy is generally not recommended as it does not alter treatment plans.
• Karyotype Analysis: Karyotype analysis (chromosome test) is recommended for women diagnosed with early menopause (under 40 years),men with severe sperm abnormalities, and couples with a history of recurrent pregnancy loss.

Less Common Tests

• Postcoital Test: This test examines how the mucus in the cervix changes during the menstrual cycle in relation to sperm. It should be done 2-12 hours after intercourse, just before expected ovulation. This test is not routinely recommended in infertility evaluations and has no proven diagnostic value.
• Endometrial Biopsy: This test provides information about ovulation and luteal phase defects. It is performed 2-3 days before the expected period. It is expensive, invasive, and does not provide information about the uterine lining's readiness for embryo implantation, making it unnecessary for evaluating ovulation.
• Basal Body Temperature: This simple test uses the body's temperature-raising effect of progesterone to assess ovulation. The body temperature is measured every morning, before any activity, throughout the menstrual cycle. A rise in body temperature occurs parallel to the LH surge and begins 2 days before it. Although it can guide ovulation detection, it is challenging and affected by many factors.

Medications or surgical methods may help achieve pregnancy, or more complex techniques may be required. These treatments are decided based on the issue of both the woman and the man. They may include ovulation treatment, insemination treatment, surgical treatments, IVF treatment, or preimplantation genetic testing (PGT).

Infertility Treatment Methods for Women

Ovulation Treatments In women who are infertile due to ovulation disorders, medications that regulate or stimulate ovulation are used. Ovulation medications work by stimulating natural hormones like Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH). These medications are also used in women with regular ovulation to produce a better egg or more eggs.

• Clomiphene Citrate: This oral medication stimulates ovulation by causing the pituitary gland to release FSH and LH. It is typically the first-line treatment for women under 39 who do not have PCOS.
• Gonadotropins: These injected medications stimulate the ovaries to produce multiple eggs. Gonadotropin medications include Human Menopausal Gonadotropin (hMG) and FSH.
• Human Chorionic Gonadotropin (hCG): This gonadotropin is used to mature eggs and trigger ovulation when the eggs are ready. The use of gonadotropins increases the risk of multiple pregnancies and preterm births.
• Metformin: Typically used for women with PCOS and insulin resistance, this drug helps reduce insulin resistance and increase the chances of ovulation.
• Letrozole: A drug in the aromatase inhibitor class, Letrozole works similarly to Clomiphene. It is usually used for women with PCOS under 39 years of age.
• Bromocriptine: This dopamine agonist is used in cases where ovulation problems are caused by excessive prolactin (hyperprolactinemia) production by the pituitary gland.

Surgical Treatments Several surgical procedures can correct problems or improve female fertility. However, due to the success of other treatments, surgical treatments are now rare. They include:

• Laparoscopic or Hysteroscopic Surgery: Performed to correct congenital anatomical abnormalities in the uterus, remove endometrial polyps, some myomas that deform the uterine cavity, or resolve pelvic or uterine adhesions.
• Tubal Surgery: If the fallopian tubes are blocked or filled with fluid (hydrosalpinx),laparoscopic surgery may be necessary. Although pregnancy rates are generally better with IVF, surgery to remove or tie off the fallopian tubes can increase the chances of pregnancy with IVF in the presence of hydrosalpinx.

Insemination Treatment Insemination treatment is a commonly used method for couples with infertility issues. On the day of ovulation, high-mobility sperm are placed into the uterus through a thin catheter. The sperm, prepared using the sperm-washing method in the lab, are delivered as close to the eggs as possible.

Insemination can be performed during natural ovulation or during ovulation stimulated with medication. It is a painless procedure that does not require hospitalization. Compared to IVF, it is easier, cheaper, more physiological, and less burdensome. It can be repeated 3-4 times until pregnancy is achieved.

In Vitro Fertilization (IVF) IVF is the process of retrieving mature eggs, fertilizing them with sperm in the lab, and then transferring the embryos to the uterus. IVF is the most effective assisted reproductive technology. IVF treatment lasts several weeks and requires daily hormone injections.

Can an Infertile Woman Get Pregnant?

Diagnosing the cause of infertility in women can be challenging. Many treatments can be applied depending on the cause of infertility. However, many infertile couples can conceive without treatment. About 95% of couples become pregnant successfully within the first two years of the treatment process.

If early menopause has occurred and there are no eggs left, if the uterus is absent by birth or surgically removed, it is not possible for the woman to get pregnant.