Infertility and Hormonal Assessment 34

Pituitary Gland Revisit

The pituitary gland plays a central role in fertility as it's the hormone control center. The brain communicates with the body through neurons and hormones. Neurons provide immediate, targeted actions to specific areas. Hormones are slow, but allow for broad influence over the entire body.

Example: Adrenaline affects the vascular system, muscles and liver. Blood flow is prioritized differently among organs depending on the situation. For example, during running, muscles receive significantly increased blood supply compared to when sitting.

Hormones heavily influence fertility; the pituitary gland and hypothalamus work as a unit.

Hormonal Assessment of Fertility

Clinical biochemistry assesses hormone levels to evaluate fertility. Specific hormone samples are taken at specific times. Other specialisms, such as hematology, may rule out contributing factors to infertility such as anemia.

Anterior and Posterior Pituitary

The pituitary divides into anterior and posterior sections. The posterior pituitary primarily releases oxytocin and antidiuretic hormone (ADH, vasopressin).

  • ADH (Antidiuretic Hormone, Vasopressin): It regulates water retention in the kidneys by controlling aquaporins. It works directly on the water levels of the body.

  • Oxytocin: Known as the trust or pair-bonding hormone, oxytocin reinforces maternal bonds. It operates through a feedforward mechanism. During childbirth, uterine wall pressure triggers oxytocin release, leading to contractions, further pressure, and continued oxytocin release until the baby is born. This mechanism is also used to induce birth medically.

Intermediate Lobe

The intermediate lobe produces melanocyte-stimulating hormone, influencing melanin production, with unclear functions in humans, potentially related to sleep.

Anterior Pituitary

The anterior pituitary produces key fertility hormones: LH (luteinizing hormone) and FSH (follicle-stimulating hormone) in both men and women. These hormones were named based on their effects in women because female cycles are more variable. The variability in hormone levels was much more noticeable in women.

  • Prolactin: While associated with fertility, prolactin primarily inhibits it. It stimulates breast development and milk production (pro-lactation). Breastfeeding raises prolactin, suppressing LH and FSH, which reduces fertility. This is observed in nature where dominant male lions kill cubs to stop lactation and restore the female's fertility.

  • Growth Hormone: It's a variable product, so levels of insulin-like growth factors produced by the liver are measured instead.

  • TSH (Thyroid Stimulating Hormone): This controls metabolism by influencing T3 and T4 release from the thyroid, affecting energy levels and weight. This hormone is important for regulation of the body's metabolism.

    • Hyperthyroidism symptoms include extreme energy and insomnia, eventually leading to exhaustion.

  • ACTH (Adrenocorticotropic Hormone): It stimulates adrenal glands to produce cortisol, the stress hormone, which is beneficial for memory formation during stressful situations but can impair memory during exams.

    • Stress response aids memory of stressors. However, prolonged stress disrupts memory consolidation, hindering exam performance.

The key hormones for assessing fertility are LH, FSH, prolactin, estrogen, progesterone (in women), and testosterone (in men).

Female vs. Male Hormone Cycles

Female cycles show significant hormone variability, unlike the relatively stable hormone levels in males. In females, LH normally stays above FSH, and can be reversed in conditions like PCOS. A key feature is the LH spike mid-cycle, triggering ovulation. The follicle becomes the corpus luteum, secreting hormones that signal pregnancy.

Estrogen peaks before the LH surge, causing it, while progesterone rises post-ovulation to prepare the endometrium for implantation, which remains elevated if pregnancy occurs.

Hormone Sampling Specifics

Due to hormone variability in females, sample timing is crucial. Samples are taken on day 3 and day 21 of the cycle to avoid LH/FSH spikes and extreme estrogen/progesterone levels.

  • Day 3: To measure baseline levels the LH, FSH, estrogen and progesterone are lowest during this phase.

  • Day 21: To measure levels when progesterone is typically at its peak.

Testosterone levels in men are about ten times higher than in women. Elevated testosterone in women can also interfere. It is important that the dates of the cycle are provided, otherwise results are useless.

Ovarian Hormone Function

  • Estrogen: Secreted by follicles, estrogen affects the uterus, vagina, and breasts, influencing secondary sexual characteristics and mediating the menstrual cycle.

  • Progesterone: Produced by the corpus luteum, progesterone maintains the uterus lining during pregnancy.

The Pill

The pill, containing progesterone and/or estrogen, mimics pregnancy. The pill maintains high levels of progesterone to prevent the release of additional oocytes. It has revolutionized society through contraception.

Male Fertility Assessment

Male fertility is assessed before female fertility due to its relative simplicity. Men produce new spermatozoa continuously, while women are born with all the oocytes they will ever have, and those oocytes are suspended in a state of paused division. Spermatozoa are constantly replaced and renewed.

Genetic disorders (e.g., Down's syndrome) are linked to a woman's age, due to the oocytes being kept in a paused division state. Oocytes are susceptible to permanent genetic damage from factors like smoking.

A semen analysis is performed to assess spermatozoa characteristics. If initial results are normal (sperm count > 5 million cells/mL with normal morphology and motility), hormone testing may not be necessary. Otherwise, LH, FSH, and testosterone levels will be measured. Prolactin is rarely tested but can inhibit male fertility at high levels. Very high levels of prolactin and normal levels of LH, FSH, and testosterone can be used to diagnose a prolactinoma.

  • Elevated LH/FSH indicates gonadal issues because the pituitary is demanding more testosterone/spermatozoa.

  • Low LH/FSH suggests hypothalamic-pituitary disorders like prolactinoma, which inhibits LH and FSH production.

  • Normal hormone levels indicate idiopathic infertility (unknown pathology), which is the most common cause.

Types of Hypogonadism

  • Hypergonadotropic Hypogonadism: High LH/FSH but low testosterone.

  • Hypogonadotropic Hypogonadism: Low LH/FSH and low testosterone.

Azoospermia is the abnormal morphology of sperm. Sexually transmitted infections (STIs) can cause scarring to tracks and can damage spermatozoa, leading to an infection.

Female Infertility Assessment

Evaluating female infertility can often be more complex than evaluating male infertility. First, day 21 progesterone is assessed.

If progesterone is normal, ovulation is occurring (unless the patient is on the pill). Further investigation then requires anatomical or post-coital factors.

  • Post-coital issues can come from spermicidal creams.

  • Anatomical issues may be related to fallopian tubes or STI-related scar tissue. Oocytes are the largest human cells and require proper transport down the fallopian tubes.

Ectopic pregnancies can also occur when the oocyte has not properly left the fallopian tube.

Endometriosis can also contribute to anatomical problems.

If progesterone is low on day 21, poor or absent ovulation is likely. Next, LH, FSH, prolactin, estradiol, and testosterone values are measured.

  • If FSH and LH are high but estradiol is low, this indicates primary ovarian failure where the ovaries are not producing enough estrogen.

  • If prolactin is high, FSH/LH are low, this suggests prolactin is inhibiting LH/FSH production. This might be caused by antidepressants that can inhibit production of prolactin.

Creatinine and liver function tests are performed to determine hormone removal since prolactin builds up with liver and kidney disease.

If testosterone is high with normal/high FSH and LH, then this is common in polycystic ovarian syndrome (PCOS). Pelvic ultrasound can look for cysts.

If FSH/LH are normal or low, possible causes include drugs, weight loss, stress, female athletes pushing their body too far, or pituitary disease. Anorexia and stress also impede female ovulation.

Ovulatory Dysfunction

Ovulatory dysfunction includes PCOS. Metformin is used to help with weight loss.
Fat tissue can aromatize the hormones and turn them into testosterone, which can encourage cysts.

Diagnosis is performed by analysis of progesterone LH, FSH and testosterone, but this may not reflect the whole story. Ultrasound analysis identifying more than ten cysts is recommended. Patients may present with irregular menstrual cycles (either oligo- or amenorrhea).

The etiology of cysts is still undertain. Multiple factors can increase the likelihood of a cyst, such as obesity. High testosterone can cause more cysts, and more cysts in turn result in a higher testosterone level. Treatments include weight loss and stress reduction.

Tubal Occlusion

Tubal occlusion, where blocked fallopian tubes, affects less than 5% of women. Scar tissue, STIs or endometriosis can cause tubal occlusions. Endometrial tissue can grow in the fallopian tubes that are difficult for oocytes to move around.

Diagnosis is normally performed with laparoscopic biopsy, ultrasound or MRI. Patients often have pelvic pain, painful menstrual cramps, abdominal/back pain, painful sex, or pain when urinating.

Treatments consist of reducing inflammation and pain and/or contraceptive pills to control fertility. In severe cases, hysterectomy can get rid of the pain at the cost of future fertility.

Iatrogenic Infertility

Iatrogenic infertility arises from medical interventions. Chemotherapy destroys rapidly dividing cells (including oocytes/spermatozoa), which can remove fertility so eggs or sperm will be removed beforehand. SSRIs inhibit dopamine release, raising prolactin and inhibiting LH/FSH.

Treatments consist of removing the relevant medication.

Summary

The pituitary gland, controlled by the hypothalamus, links the CNS to the body.

Hormonal assessment of fertility depends on males vs. females. In males it is LH, FSH and testosterone, while in females it is LH, FSH, testosterone, estrogen, progesterone and prolactin. In females, it is important to have a day 3 and day 21 sample. Random LH samples are useless.

Common causes of infertility include polycystic ovary syndrome, thyroid issues and endometriosis. Large amounts of iatrogenic causes can also lead to subfertility and infertility, such as chemotherapy and antidepressants. There are also traumatic causes for males who receive damage to the testicles.