What is the medical management of infertility?

Medical Management of Infertility

Initial Evaluation Algorithm

Both male and female partners must undergo concurrent assessment from the outset—delaying evaluation of either partner leads to unnecessary, costly, and invasive treatments for the other. 1, 2

Male Partner Evaluation

• Obtain semen analysis as the first-line test (one or more samples), which is a strong recommendation for all infertility evaluations 1, 2
• Collect a detailed reproductive history including: duration of infertility attempts, previous pregnancies with any partner, childhood illnesses (especially cryptorchidism or mumps orchitis), sexual function and frequency, medication use (especially anabolic steroids or testosterone), occupational exposures to heat or toxins, and lifestyle factors (smoking, alcohol, recreational drugs) 3, 4
• Perform physical examination focusing on: testicular size and consistency, presence and consistency of vas deferens bilaterally, varicocele detection (examined standing), epididymal abnormalities, and secondary sexual characteristics 3
• Men with any abnormal semen parameters require referral to a male reproductive specialist for complete evaluation and directed testing 1, 2
• Obtain hormonal evaluation including serum testosterone, FSH, and LH when semen analysis is abnormal 3

Female Partner Evaluation

• Document ovulation using home urinary LH kits or serum progesterone level at cycle day 21 5, 6
• Obtain reproductive history including: menstrual cycle regularity and characteristics, previous pregnancies and outcomes, pelvic inflammatory disease or STD history, previous pelvic surgeries, dyspareunia, galactorrhea, and hirsutism 1
• Perform physical examination including: BMI calculation, thyroid examination, breast examination for galactorrhea, and pelvic examination for anatomic abnormalities 1
• Evaluate uterus and fallopian tubes with hysterosalpingography in women without risk factors for tubal disease 4, 6
• For women with history of endometriosis, pelvic infections, or ectopic pregnancy, proceed directly to hysteroscopy or laparoscopy rather than hysterosalpingography 6
• In women ≥35 years, perform ovarian reserve testing with day 3 FSH and estradiol levels, clomiphene citrate challenge test, or pelvic ultrasound for antral follicle count 7

Treatment Based on Diagnosis

Ovulatory Dysfunction (25% of cases)

For anovulation or oligo-ovulation, initiate clomiphene citrate starting on cycle day 5 for up to 6 total cycles (including 3 ovulatory cycles). 5, 8

• Clomiphene citrate is FDA-approved specifically for ovulatory dysfunction in women desiring pregnancy 5
• 70% of anovulatory women have polycystic ovary syndrome, which responds well to ovulation induction 8
• Alternative agents include letrozole (aromatase inhibitor) or gonadotropins for clomiphene-resistant cases 8
• Critical warning: Ensure patient is not pregnant, has no ovarian cysts (except PCOS), has no abnormal vaginal bleeding, and has normal liver function before starting clomiphene 5
• Perform pelvic examination before each treatment course to exclude ovarian enlargement 5

Male Factor Infertility

Treatment depends on specific diagnosis identified by the reproductive specialist: 2, 3

• For clinical varicocele with abnormal semen parameters and unexplained infertility (when female partner has good ovarian reserve), perform varicocelectomy 2
• For hypogonadotropic hypogonadism, treat with gonadotropin therapy after determining etiology 2
• Absolutely avoid exogenous testosterone in men seeking fertility—it suppresses spermatogenesis 2, 3, 9
• For obstructive azoospermia, options include transurethral resection of ejaculatory ducts or surgical sperm extraction with similar success rates for epididymal versus testicular retrieval 2
• For elevated sperm DNA fragmentation, consider testicular sperm extraction for ICSI, which shows improved clinical pregnancy rates and reduced pregnancy loss 2, 9
• Treat male accessory gland infections to improve sperm quality, and refer sexual partners of patients with STD-related infections 2

Tubal Factor Infertility

• Tubal disease requires subspecialty referral for surgical repair or in vitro fertilization 7, 6
• Surgical repair may be attempted for localized disease, but IVF is often more successful 7

Endometriosis

• Treatment options include surgical intervention, ovulation induction with intrauterine insemination, or in vitro fertilization 7
• Choice depends on disease severity, age, and ovarian reserve 7

Unexplained Infertility (15% of cases)

Begin with 3-4 cycles of ovarian stimulation with intrauterine insemination before proceeding to IVF. 8

• This stepwise approach balances cost-effectiveness with success rates 8
• For women ≥38-40 years, consider proceeding directly to IVF due to declining ovarian reserve and time constraints 8
• IVF provides approximately 37% live delivery rate per initiated cycle, with results closely related to female age 2

Severe Male Factor (e.g., severe teratozoospermia)

Proceed directly to IVF with intracytoplasmic sperm injection (ICSI) rather than attempting IUI. 9

• IUI has reduced success with severe morphology defects (>90% abnormal forms) 9
• ICSI bypasses the natural selection barriers that severe teratozoospermia creates 9

Assisted Reproductive Technologies

• IUI and IVF with or without ICSI are options when natural conception fails 2
• For severe oligozoospermia or azoospermia, IVF with ICSI using ejaculated, epididymal, or testicular sperm 2
• Overall success rate approaches 50% with appropriate treatment selection 7

Fertility Preservation for Cancer Patients

All men with cancer must be offered sperm cryopreservation before gonadotoxic treatment or ablative surgery. 2

• Ejaculated semen preservation is the most cost-effective strategy 2
• For severe oligozoospermia or azoospermia, perform surgical sperm extraction (onco-TESE) 2
• Use contraception during and for at least 6 months after completion of gonadotoxic treatment 2

Genetic Considerations

• Perform karyotype testing for males with severe oligozoospermia or non-obstructive azoospermia 3
• Test for Y-chromosome microdeletions in severe oligozoospermia or azoospermia 3
• Perform CFTR mutation analysis if congenital bilateral absence of vas deferens is detected 3
• Genetic counseling is essential before proceeding with ART in these cases 3

Lifestyle Modifications (Implement Immediately)

• Smoking cessation—tobacco reduces fertility in both partners 1, 3, 4
• Weight optimization—obesity and extreme thinness reduce fertility rates 1, 4
• Limit alcohol intake and avoid recreational drugs 1, 4
• Reduce caffeine consumption to <5 cups daily 1
• Avoid excessive heat exposure to testes (hot tubs, saunas, tight underwear) 3
• Avoid commercially available vaginal lubricants which may reduce fertility 1

Critical Pitfalls to Avoid

• Do not delay specialist referral waiting for a third semen analysis—two abnormal results warrant full evaluation 3
• Do not prescribe testosterone to men desiring fertility—it causes azoospermia 2, 3, 9
• Do not assume "idiopathic infertility" without complete workup—over 50% have identifiable causes 3
• Do not recommend antioxidants or herbal therapies as primary treatment—insufficient evidence supports their use 3, 9
• Do not use clomiphene citrate for male infertility—it is not effective and may cause testicular tumors 5
• Do not evaluate only one partner—concurrent assessment prevents unnecessary treatments 1, 2, 3

Timing Considerations

• Begin evaluation after 12 months of regular unprotected intercourse 7, 4, 8
• Initiate evaluation earlier (after 6 months) if: female partner is ≥35 years, history of oligo-amenorrhea, known/suspected uterine or tubal disease, known/suspected endometriosis, or known male subfertility 1, 7
• Consider evaluation in couples with failed ART cycles or ≥2 recurrent pregnancy losses 1