Infertility

Conditions for Normal Implantation and Conception

For a pregnancy to successfully occur, a very specific chain of events must be perfectly executed. The following conditions must be fulfilled:

• There should be two partners actively involved and willing.
• They must engage in regular, unprotected coitus without any form of contraception.
• They must use the right sexual route (vaginal penetration with ejaculation).
• The female should be within the active childbearing age (14 to 49 years).
• The male must release healthy semen containing a normal count of motile and morphologically normal spermatozoa.
• A normal, healthy ovum (egg) must be released from the female's ovary (ovulation).
• The ovum must unite with the sperms in the fallopian tube to be fertilized.
• The fertilized ovum (zygote) must successfully travel to and implant in the healthy endometrium of the uterus.

Causes of Infertility in Males

Male factor infertility accounts for a significant portion of infertility cases. The causes range from psychological to severe physiological and genetic abnormalities:

• Sperm Abnormalities: The release of immature sperms, structurally abnormal sperms, too few sperms (oligospermia), or sperms that are too slow in movement (asthenospermia).
• Ejaculatory Issues: Poor ejaculation, premature ejaculation, or complete failure to ejaculate. Retrograde ejaculation is a specific condition where semen is ejaculated backward into the bladder instead of out through the urethra (assessed by urinalysis after ejaculation).
• Extreme Heat: An increase in the temperature of the testes from a prolonged fever, tight clothing, or occupational exposure to excessive heat can greatly reduce sperm count, reduce the vigor of sperm movement, and increase the number of abnormal sperms in the semen.
• Hydrocele: Excessive collection of fluid in the scrotum. This extra fluid creates pressure and alters the environment, preventing the adequate production of sperms.
• Varicocele: Varicose (swollen and enlarged) veins of the scrotum. This abnormality prevents the proper supply and drainage of blood from the testes, thus raising the scrotal temperatures and drastically reducing the rate of sperm production. It also affects the quality of ejaculation.
• Medications & Drugs: Certain drugs cause failure in erection or spermatogenesis. Examples include amoebicides (for amoebiasis), anti-hypertensives like Aldomet (Methyldopa), and diabetic drugs. Nitrofurantoin (an antibiotic) can cause degenerative changes in sperms.
• Infections: Diseases like Mumps in adult males can cause Orchiditis (severe inflammation of the testes), leading to permanent testicular damage and sterility.
• Hormonal Imbalance: Inadequate production of testosterone from the Leydig cells can result in immature sperms and poor libido.
• Lifestyle Factors: Excessive smoking, chronic alcohol consumption, severe obesity, and extreme depression or stress heavily inhibit spermatogenesis and sexual performance.
• Toxic Exposure: Chronic exposure to toxic industrial chemicals, heavy metals, or radiations physically damages the germinal epithelium of the testes, halting spermatogenesis.

Genetic Factors in Males

• Klinefelter’s Syndrome: A chromosomal genetic syndrome where a male has 47 chromosomes with an extra X chromosome (47, XXY instead of the normal 46, XY). The loss of a dominant Y-chromosome effect leads to a feminine body build. It presents with gynaecomastia (enlarged breasts), testicular atrophy (shrinking testes), azoospermia (zero sperms), and complete infertility. The testicular atrophy is a result of peritubular fibrosis commencing in childhood and progressing until all seminiferous tubules are replaced by useless fibrous tissue.

Causes/Factors of Infertility in Females

Female infertility is deeply complex and is clinically best discussed under the following distinct headings:

1. Defective Implantation & Tubal Factors

Tubal blockage is the major cause of infertility, especially in Uganda, contributing to 60 – 70% of cases.

• Pelvic Inflammatory Disease (PID) & Salpingitis: Infection of the fallopian tubes caused by Gonorrhoea, Chlamydia, Tuberculosis, or pelvic peritonitis (e.g., from a burst appendix) after an abortion or delivery. This damages the delicate ciliated tubal epithelium. In severe cases, it causes total tubal blockage. This mostly occurs at the outer end of the tube where the fimbriae adhere together, but it is also seen in the very narrow, interstitial part of the tube.
• Ectopic Risks: When the tubes are not completely blocked, fertilization of the ovum may still take place. However, because of the damage to the ciliated epithelium, the fertilized ovum cannot be carried down the tube to the uterus, resulting in a dangerous Ectopic Pregnancy.
• Uterine Abnormalities: Congenital malformations such as having no uterus, a bicornuate uterus (heart-shaped), or a Didelphys uterus (two completely separate horns and cervixes).
• Uterine Fibroids: Gross fibroids create an irregular, bumpy implantation surface or physically block the fallopian tube ostia.
• Uterine Synechiae (Asherman's Syndrome): Severe inflammation of the endometrium (endometritis) or scarring caused by over-curetting of the uterus during a D&C, or from surgeries like myomectomy, leads to the walls of the uterus sticking together (intrauterine adhesions).
• Endometriosis: A painful condition where patches of endometrial-like tissue develop outside the uterine cavity in abnormal locations (ovaries, fallopian tubes, abdominal cavity). This tissue grows and bleeds with hormonal stimulation, causing massive inflammation, scar tissue, pelvic adhesions, and infertility.
• Cervical & Vaginal Issues: Stenosed (narrowed) cervix due to trauma/surgery. Acquired or congenital Gynaeatresia (a very small vaginal hole with a blind end), septate vagina, or a completely rigid hymen preventing penetration.
• Infections & Contraceptives: Severe Trichomonas vaginalis infections (evidence of cause noted in Zambia). Prolonged use of barrier contraceptives (condoms, IUDS, Spermicides) without recognizing underlying fertility delays.

2. Endocrine (Hormonal) Disorders

• Hypothalamic-Pituitary Inefficiency: Stress, extreme weight loss, or excessive weight gain causes an unstable cerebrum and hypothalamus. This alters dopamine or noradrenaline transmission. Certain drugs (Rawolfia, phenothiazines, Metoclopramide) also suppress hypothalamic function, leading to failure of ovulation.
• Hyperprolactinaemia: A pituitary tumor (micro or macroadenoma) leading to the production of excessive Prolactin hormone. Elevated prolactin is normal during lactation (causing lactational amenorrhea), but if a woman is not lactating, this hormone suppresses GnRH, causing total anovulation.
• Thyroid & Adrenal Function: Hyperthyroidism, Hypothyroidism, Cushing's syndrome, or Congenital Adrenal Hyperplasia all cause severe hormonal imbalances resulting in anovulation.
• Age & Menopause: Fertility steeply declines with advanced age. Postponement of childbearing for careers frequently leads to age-related ovulatory decline.

3. Ovarian Causes

• Resistant Ovary Syndrome: Absence of FSH receptors in the ovarian follicle leads to the complete failure of the ovary to respond to gonadotrophins.
• Polycystic Ovarian Syndrome (PCOS): Disturbance in the interaction between FSH and the follicle results in an abnormal enzyme reaction. The follicles fail to rupture (anovulation), and the ovary becomes enlarged and multicystic. Without ovulation, the endometrium lacks secretory changes, and cervical mucus remains thick and impenetrable by sperms.
• Ovarian Damage/Absence: Congenital lack of eggs/follicles, premature menopause, surgical removal of the ovary by mistake, or destruction of the ovarian substance by deep infections like Mumps.
• Radiation Exposure: Chronic or excessive exposure to radioactive substances or X-rays physically damages and mutates the delicate ova.

4. Defective Transport & Hostility

• Cervical Hostility: A condition in which the cervical mucus is totally unreceptive to spermatozoa. The mucus either blocks their progressive advance or actively kills them. This may be due to chronic cervical infection or the presence of specific Sperm Antibodies (an allergic immune response to the man's sperms).
• Vaginal pH: A highly acidic vaginal pH rapidly destroys the motility of the sperms before they can enter the protective cervix.

5. Physical, Psychological & Systemic Causes

• Psychological & Sexual Dysfunction: Dyspareunia (severe painful sexual intercourse due to psychological or physical factors) and Vaginismus (involuntary spasms of the pelvic floor muscles preventing penetration).
• Wrong Timing: Having sexual intercourse exclusively during infertile periods (miscalculating the ovulation window).
• Systemic Diseases: Chronic, uncontrolled diseases such as Diabetes Mellitus, severe Hypertension, and Renal Failure drastically lower fertility chances.
• Turner’s Syndrome (Genetic): Caused by the complete deletion or abnormality in one of the female's two X chromosomes (Karyotype 45, XO). These females present with complete ovarian failure (streak ovaries), widely spaced nipples, cardiovascular problems, squints, hypothyroidism, and diabetes mellitus. They face absolute infertility and require estrogen therapy in adult life.

General Investigations & Evaluation

All couples complaining of infertility must be investigated together. The length and depth of the investigations will vary depending on the initial findings.

Evaluation in Women

1. Comprehensive History & Physical Examination

• Menstrual History: Age of menarche, length, and regularity of the menstrual cycles.
• Gynaecological History: Previous contraceptive use, history of D&C, salpingectomy, abortions, or highly suggestive symptoms of PID.
• Obstetric History: Any previous pregnancies and the exact number of children fathered specifically by her current partner.
• General Health: Extremely thin women face amenorrhoea due to lack of body fat. Very obese women face anovulation because the ovary cannot secrete enough estradiol, converting androgens into excess estrone instead. Age is strictly noted (above 50 is generally menopause).
• Physical Inspection: Check for visual field deficits (suggestive of a large pituitary tumor pressing on the optic chiasm). Check pubic and body hair distribution (presence of male-pattern hair / virilism suggests excess androgens).
• Vaginal Examination: Check the normality of the vaginal canal, cervix, and uterus. Confirm pelvic anatomy with an ultrasound.

2. Hormonal & Special Tests

• Progesterone Levels: In a standard 28-day cycle, blood is drawn on Day 21 (or 1 week before the expected period). A progesterone level of more than 20 mmol/L firmly confirms that ovulation took place.
• FSH and LH Levels: Checked to identify premature menopause, ovarian failure, or polycystic ovaries.
• Basal Body Temperature (BBT): The woman takes her oral temperature every morning upon waking, before any physical activity. A sustained rise of about 0.5°C in the last 14 days of the cycle indicates ovulation has occurred. Monitored for 6 months.
• Cervical Mucus Examination: Mid-cycle ovulatory mucus is clear, copious, and stretches into a fine thread (called Spinnbarkeit). On a glass slide, it dries to form a characteristic fern pattern under the microscope.
• Post Coital Test (Huhner’s Test): Carried out exactly at ovulation. 2 to 8 hours after unprotected intercourse, cervical mucus is withdrawn using a wire loop/pipette, placed on a warm slide, and examined. Normally, a large number of progressively motile sperms are seen. Absence or dead sperms indicate cervical hostility or sperm antibodies.
• Prolactin Tests: If prolactin is higher than 800 mU/L, a CT scan of the pituitary fossa is mandatory to exclude a prolactin-producing adenoma.
• Endometrial Biopsy: Done 10-12 days after ovulation. Histology will prove if the glands have undergone necessary secretory changes to support an embryo.

3. Tubal Patency Tests

• Laparoscopy & Dye Test: The gold standard. A premenstrual procedure combining visual inspection of the pelvis with the injection of dilute methylene blue dye through the cervix. The uterus distends, and if the tubes are patent (open), the dye freely spills from the fimbrial ends. No spill indicates a block. (Pregnancy must be ruled out first).
• Hysterosalpingogram (HSG): An opaque radio-aqueous solution is injected through the cervix. An X-ray is taken to visualize the uterine cavity and tubal patency. This is done between day 5 and 10 of the cycle (after bleeding stops but before ovulation).
• Tubal Insufflation: An older, highly unreliable method where Carbon Dioxide (CO2) gas is passed into the uterus. Patency is assumed if the gas is heard via auscultation or confirmed on X-ray.
• Transvaginal Ultrasound (TVS): Gives clear images of the ovaries and uterus. Contraindications: Suspected pregnancy, severe cervical erosion, active pelvic infection, DUB, or serious heart/lung diseases. Risks: Embolism or ascending infection.

Evaluation in Men

• General Exam: Check for severe obesity, diabetes, and hypertension. Evaluate male hair distribution and genital development. Check for surgical scars (e.g., undescended testis operation before puberty).
• Breast Check: Enlargement (gynaecomastia) indicates abnormally high estrogen levels or Klinefelter's syndrome.
• Testicular Exam: Assess the exact size, consistency, and situation of the testes in the scrotum.
• Hormonal Blood Tests: Evaluate FSH, LH, and Testosterone levels to rule out endocrine failure.

Normal Seminal Fluid Analysis Findings

A fresh semen sample is analyzed. Normal parameters must meet or exceed the following:

• Volume: ≥ 2.0 to 2.5 ml.
• pH: 7.0 to 8.0 (Slightly alkaline to survive the acidic vagina).
• Total Sperm Count: More than 20 million per ml.
• Liquefaction: Must be completely liquefied within 1 hour.
• Motility: ≥ 50% must have strong, forward, progressive motility.
• Morphology: ≥ 30% or more must have a perfectly normal shape.

Treatment of Infertility

Treatment is strictly tailored according to the identified underlying cause.

General Preventive Measures & Counseling

• Stop all smoking and significantly reduce alcohol consumption.
• Adopt a proper, highly nutritious diet to manage weight (obesity or extreme thinness).
• Educate the couple on meeting at the exact right time (tracking the fertile ovulation window).
• Actively reduce psychological stress, marital tension, and provide deep psychological counseling to prevent depression, divorce, or polygamy.

Treatment in Women

1. Chemotherapy for Anovulatory Infertility

• Clomiphene Citrate (Clomid): Induces ovulation by stimulating the Hypothalamic-Pituitary system.
  • Dosage: 50mg daily for 5 days, starting on the 2nd day of menstruation. If ovulation fails, a second course of 100mg daily for 5 days is given (starting as early as 30 days later). Generally, 3 courses are adequate to assess efficacy.
  • Side Effects: Ovarian Hyperstimulation Syndrome (OHSS), multiple pregnancies (twins/triplets), visual disturbances, hot flushes, heavy abnormal bleeding (menorrhagia), hair loss, depression, dizziness, and nausea.
• Tamoxifen: 20mg daily on days 2, 3, 4, and 5 of the cycle. Dose may be increased to 40mg then 80mg to stimulate ovulation.
• Bromocriptine (Parlodel, Dopagon): For hyperprolactinaemic infertility. It inhibits the synthesis and release of prolactin from the pituitary.
  • Dosage: Initially 1.25mg at bedtime, gradually increased to 2.5mg three times a day with food. Max 30mg daily.
  • Side Effects: Severe nausea, hypotension, dizziness, nasal congestion, fatigue, and dry mouth.
  • Interactions: Erythromycin increases its toxicity. Antipsychotics and Metoclopramide antagonize its effect.
• Luteinizing Hormone (LH) / GnRH Pumps: Given via a subcutaneous/IV syringe pump releasing 10-25 micrograms every 90 minutes.
• HCG & HMG (Pregnyl / Metrodin): Synthetic Human Chorionic Gonadotrophin or Human Menopausal Gonadotrophin triggers ovulation when Clomiphene fails.

2. Surgical Measures in Women

• Salpingolysis: Dividing peritubal adhesions around the ampullary ends of the tubes to restore free movement.
• Salpingostomy: Surgically turning back the fimbriae to create a brand new opening for a blocked tube.
• Tubal Anastomosis & Repair: Coring out the blocked segment (e.g., at the isthmus) and intricately re-stitching (anastomosing) the healthy ends back together.
• Myomectomy: Surgical removal of uterine fibroids to clear the implantation space.

Treatment in Men

• Medical: Human Gonadotrophin Therapy or Clomiphene Citrate to forcibly stimulate sperm production. Testosterone therapy to stimulate sexual desire (libido) — Note: Do not give exogenous testosterone if the primary issue is impaired spermatogenesis, as it can suppress natural sperm production further.
• Surgical: Repair of inguinal hernias, correction of undescended testis, or Varicocelectomy (surgical ligaturing of the internal spermatic vein to reduce testicular heat and pooling). Relief of reproductive tract obstructions.

Assisted Reproductive Technologies (ART) & Other Options

In Vitro Fertilization (IVF)

Developed in 1978 (Robert Edwards won the Nobel Prize for this). IVF bypasses blocked fallopian tubes by fertilizing the egg outside the body.

• Process: The woman's ovaries are hyper-stimulated using GnRH agonists and FSH to produce multiple eggs. An HCG "trigger shot" is given. Eggs are retrieved via ultrasound-guided transvaginal aspiration exactly between 34 and 36 hours (just before follicle rupture at 38-40 hrs).
• Fertilization: The retrieved eggs are mixed with purified, washed sperms (to remove microbes/HIV) in a laboratory dish.
• Transfer: The healthiest resultant embryos are carefully transferred directly into the mother's uterus. (Caution: Often results in multiple pregnancies, and ovarian hyperstimulation must be monitored).

Intracytoplasmic Sperm Injection (ICSI)

Performed alongside IVF for severe male infertility. If sperms are very low in number, highly abnormal, or unable to penetrate the egg wall, a single healthy sperm is captured in a microscopic needle and injected directly into the cytoplasm of the egg.

Other Alternatives

• Surrogate Mothers: If a woman lacks a functional uterus, her own IVF embryo (using her egg and husband's sperm) is implanted into another woman's uterus. The surrogate carries the pregnancy and hands the baby over to the genetic parents after birth.
• Artificial Insemination by Donor (AID): If the male partner is completely sterile (azoospermia), semen from a healthy, anonymous fertile donor is introduced into the woman's reproductive tract during ovulation.
• Adoption: Couples can legally apply to an adoption center to adopt a child of their choice if medical treatments fail.

Nursing Diagnoses & Care for Infertility

The psychological toll of infertility is massive. The midwife/nurse plays a crucial role in providing holistic care:

• Anxiety and Fear: Related to unknown invasive diagnostic procedures, complex treatments, and unpredictable outcomes, evidenced by the patient’s constant verbalization of worry. (Intervention: Provide clear, empathetic explanations of all procedures).
• Low Self-Esteem & Grief: Related to the inability to conceive, evidenced by low mood, crying, feeling "inadequate," and social isolation. (Intervention: Offer therapeutic communication, refer to support groups).
• Knowledge Deficit (Reproductive Process): Related to the complex process of ovulation, fertile windows, and proper sexual relationship timing, evidenced by inadequate verbalization. (Intervention: Teach BBT charting, fertile period calculations, and sexual health).
• Knowledge Deficit (Anatomy/Causes): Related to the physical causes of infertility, evidenced by misconceptions. (Intervention: Use anatomical charts to explain tubal blockages, sperm counts, etc.).

References

• Myles, M. (Latest Edition). Textbook for Midwives. Churchill Livingstone Elsevier.
• Uganda Ministry of Health. (2001). Midwifery Handbook and Guide to Practice (11th ed.). Kampala, Uganda.
• Stanfield, P., Beladia, & Versluys. (2004). Child Health: A Manual for Medical and Health Workers in Health Centres and Rural Hospitals (2nd ed.). English Press Limited, Nairobi.
• Local Clinical Guidelines and Training Manuals for the Diploma in Midwifery Extension Program (UNMEB).