Secondary infertility: why pregnancy may not occur again

Secondary infertility is a condition that can affect any couple who already have children. It is not just a medical term but a reality that many face.

This condition means that previous pregnancies were successful, but now, despite regular unprotected sexual activity, the couple cannot conceive within a year. If the woman is over 35, this period shortens to six months, making the issue even more urgent. What has changed? Why, despite hopes and plans, has conceiving again become more difficult? Let’s explore this in more detail.

Statistics show that about 10–15% of couples who have already become parents face difficulties conceiving a child. While this number may seem small, it actually means that for every ten couples who have experienced the joy of parenthood, one may encounter unexpected obstacles on the path to conceiving again.

To better understand the nature of secondary infertility, let’s look at the main causes that can affect fertility.

Possible Causes of Secondary Infertility

1. Age-related changes

Age is one of the most important factors affecting the likelihood of conception. Research shows that female fertility begins to decline after age 30, and after 35, this process becomes more pronounced. Egg quality decreases, reducing the chances of conception. For example, women aged 35–39 may have only a 15–20% chance of conceiving per cycle. Men also experience a decline in sperm quality with age, which can negatively affect fertility.

2. Medical conditions that can cause secondary infertility

2.1 Endometriosis

Endometriosis is a chronic condition characterized by the growth of endometrial tissue outside the uterus. This condition can affect fertility in several ways:

1. Inflammation and adhesions: Endometriosis causes inflammation, leading to adhesions in the pelvic organs. This can hinder the passage of the egg through the fallopian tubes and reduce the likelihood of fertilization.
2. Hormonal changes: Hormonal imbalance associated with endometriosis can disrupt normal ovulatory cycles and egg quality.
3. Egg quality: Studies show that women with endometriosis have reduced egg quality due to inflammation and impaired ovarian blood supply.

2.2 Polycystic Ovary Syndrome (PCOS)

PCOS is an endocrine disorder characterized by abnormal ovarian function and elevated androgen levels. It can lead to:

• Anovulation: Women with PCOS often have irregular periods and no ovulation, directly reducing the chance of conception.
• Metabolic disturbances: PCOS is associated with insulin resistance, which can affect hormonal balance and reproductive function.
• Cellular changes: Elevated androgens can negatively affect follicle development in the ovaries, leading to cyst formation.

2.3 Uterine Fibroids

Uterine fibroids are benign tumors that develop in the uterine muscle. They can cause secondary infertility by:

• Deforming the uterine cavity, making embryo implantation more difficult.
• Reducing blood supply to the uterus and endometrium, affecting its ability to sustain a pregnancy.

2.4 Fallopian Tube Blockages

Tube patency is critical for conception as fertilization occurs in the tubes. Main causes of blockages include:

• Inflammatory diseases: Infections such as chlamydia or gonorrhea can cause inflammation and adhesions that block the tubes.
• Surgical procedures: Pelvic surgeries can lead to adhesions that impair tube function.
• Endometriosis: As mentioned, endometriosis can cause adhesions leading to blockages.

2.5 Infections

Reproductive tract infections can significantly reduce fertility. Inflammatory conditions include:

• Gonorrhea and chlamydia: These infections can cause inflammation of the uterus and its appendages, leading to adhesions and reduced fertility.
• Bacterial vaginosis: This condition can affect vaginal flora and trigger inflammation, complicating conception.

2.6 Hormonal imbalances causing secondary infertility

Hormonal disorders are a major cause of secondary infertility, as hormones play a crucial role in regulating the female reproductive system. Normal ovarian function, menstrual cycles, and the ability to conceive depend on complex interactions of various hormones regulated by the endocrine system. Let’s examine how specific hormonal disturbances can affect fertility.

Thyroid Dysfunction

The thyroid gland produces hormones that regulate metabolism and energy balance. Dysfunction can appear as hypothyroidism or hyperthyroidism:

• Hypothyroidism: Low thyroid hormone levels can reduce FSH and LH, essential for normal ovulation. Women may experience irregular cycles and anovulation, lowering conception chances. Even mild thyroid dysfunction may reduce fertility.
• Hyperthyroidism: Excess thyroid hormones, as in Graves’ disease, can cause anxiety, weight loss, and irregular cycles. Elevated prolactin may block ovulation. Treatment may involve medication or surgery, impacting reproductive function.

Hormones associated with secondary infertility

Prolactin

Prolactin, secreted by the pituitary gland, regulates lactation. Excessive prolactin (hyperprolactinemia) can cause:

• Anovulation: High prolactin disrupts gonadotropin balance (FSH and LH), preventing ovulation.
• Menstrual irregularities: Women may have irregular cycles or amenorrhea, complicating conception.

Androgens (male sex hormones)

Androgens like testosterone naturally exist in women at lower levels. Excessive androgens, as in PCOS, can:

• Disrupt ovulation: High androgen levels impair follicle development, leading to anovulation.
• Cause menstrual irregularities: Increased androgens may lead to irregular cycles, acne, and oily skin.

Gonadotropins

Gonadotropins regulate ovarian function:

• FSH: Stimulates follicle growth. Low FSH can cause insufficient ovarian stimulation and anovulation.
• LH: Regulates ovulation. Low LH can disrupt cycles, leading to absent or irregular ovulation.

Insulin

Insulin, produced by the pancreas, regulates glucose metabolism. Disorders affect reproduction via:

• Insulin resistance: Common in PCOS, leading to high insulin levels that stimulate excess androgen production, causing anovulation.
• Metabolic effects: Often associated with obesity, further complicating reproductive function.

How stress relates to secondary infertility

Stress is not just emotional; it’s a physiological process that can significantly affect reproduction. Stress activates the HPA axis, increasing cortisol, which can lead to insulin resistance, weight gain, and hormonal imbalance.

Key stress-related effects include:

Hormonal changes

• Impact on gonadotropins: Cortisol suppresses FSH and LH, impairing ovulation.
• Androgens: Chronic stress may increase androgen secretion, affecting ovulation, especially in women with PCOS.
• Estrogen and progesterone: Stress disrupts normal cycles, lowering progesterone and impairing implantation.

Menstrual cycle changes

• Irregular cycles or amenorrhea, complicating ovulation prediction.
• Anovulation, directly preventing conception.

Psychological impact

• Anxiety and depression may alter hormones and fertility.
• Emotional stress can reduce motivation and affect relationships, increasing overall stress.

Lifestyle changes

• Poor nutrition under stress can cause nutrient deficiencies affecting reproductive health.
• Reduced physical activity harms overall health and hormonal balance.
• Alcohol or smoking use under stress negatively affects fertility.

Recommended evaluations for couples struggling to conceive

A comprehensive assessment is necessary to identify causes of secondary infertility.

1. General medical examination

• Medical history: Previous pregnancies, complications, chronic illnesses affecting fertility (diabetes, hypertension, endocrine disorders).
• Family history: Reproductive history of both partners, including genetic conditions.

2. Hormonal tests

• FSH and LH: Measured days 2–5 of the menstrual cycle to evaluate ovarian function.
• Estradiol: Measured days 18–21 to assess ovarian activity and implantation readiness.
• Progesterone: Measured in the luteal phase (7–10 days before expected menstruation) to evaluate corpus luteum function.
• Prolactin: High levels can block ovulation and indicate endocrine issues.

For men:

• Testosterone: Low levels may reduce sperm quantity and quality.
• Gonadotropins (FSH and LH): Assess for endocrine dysfunction.

3. Reproductive system evaluation

• Ultrasound of pelvic organs, thyroid, and breasts to assess anatomy and detect abnormalities.
• Hysterosalpingography (HSG) to check fallopian tube patency.
• Laparoscopy if other tests suggest potential issues, allowing visualization and therapeutic intervention.

4. Semen analysis

• Assess volume, concentration, motility, and morphology.
• Additional tests if infection or hormonal issues are suspected.

5. Genetic testing

• Karyotyping to detect chromosomal abnormalities affecting fertility.
• Specific mutation testing for genetic causes of reproductive problems.

6. Psychological assessment

• Evaluate stress, anxiety, and depression, which may affect reproductive function. Counseling may help address these issues.

Secondary infertility can be an emotional shock, causing feelings of hopelessness, anxiety, and guilt. Having prior experience with parenthood highlights the challenge when conception does not occur again as expected.