Definition (ASRM 2023). Infertility is a disease or condition marked by inability to achieve a successful pregnancy based on history, age, examination, or testing, or the need for medical intervention (including donor gametes or embryos) to conceive. For clinical timing:

• Evaluate after 12 months of regular unprotected intercourse if the female partner is under 35
• Evaluate after 6 months if she is 35 or older
• Evaluate immediately if over 40 or with a known cause (e.g., amenorrhea, known tubal disease, endometriosis, prior chemotherapy, known male problem)

Primary infertility = never conceived; secondary = infertility after a previous pregnancy. Female age is the single strongest predictor of fertility because egg number and quality fall, especially after 35.

Conception requires: ovulation of a healthy egg, sperm of adequate number and function, open fallopian tubes, a receptive uterine cavity, and cervical mucus that allows sperm passage. A male factor contributes in roughly half of couples, so both partners are evaluated together.

Female causes

Male causes

• Impaired sperm production (spermatogenesis) — the most common male cause: low count, poor motility, abnormal shape; causes include varicocele, heat, smoking, obesity, infection (mumps orchitis), chemotherapy
• Hypothalamic–pituitary problems: Kallmann syndrome (congenital GnRH deficiency with anosmia) → hypogonadotropic hypogonadism
• Exogenous testosterone or anabolic steroids — suppress FSH and LH and therefore sperm production
• Genetic: Klinefelter syndrome (47,XXY), Y-chromosome microdeletions, cystic fibrosis gene mutations (absent vas deferens)
• Obstruction (prior vasectomy, infection), ejaculatory dysfunction

Immunologic factors — antisperm antibodies can impair sperm motility, passage through cervical mucus, and binding to the egg. Unexplained infertility is diagnosed when standard testing is normal.

History (both partners)

• Duration of infertility, frequency and timing of intercourse (the most basic first question), use of lubricants
• Menstrual history: cycle length and regularity (regular cycles usually mean ovulation), dysmenorrhea, dyspareunia (endometriosis)
• Prior pregnancies, STIs/PID, pelvic or abdominal surgery, cancer treatment
• Medications and substances: testosterone, anabolic steroids, tobacco, alcohol, cannabis
• Occupational exposures (heat, chemicals), weight changes, exercise, stress

Physical findings

• Signs of androgen excess (hirsutism, acne), acanthosis nigricans, obesity (PCOS)
• Galactorrhea (hyperprolactinemia), thyroid enlargement
• Male: testicular size, varicocele, absent vas deferens, virilization

Basic evaluation = ovulation + tubes/uterus + semen analysis

WHO 2021 semen reference limits (lower 5th percentile)

Values just below these limits do not prove infertility, and values above them do not guarantee fertility; results are interpreted together.

The postcoital test and routine endometrial biopsy for "luteal phase defect" are no longer recommended — they do not predict pregnancy.

Lifestyle: healthy weight (even 5–10% weight loss can restore ovulation in PCOS), stop smoking, limit alcohol, keep caffeine under about 200 mg/day, folic acid 0.4–0.8 mg daily, men avoid testosterone and heat exposure. Intercourse every 1–2 days in the fertile window (the 6 days ending on ovulation day).

Ovulation induction and related drugs

Procedures

• Intrauterine insemination (IUI) — washed sperm placed in the uterus near ovulation
• In vitro fertilization (IVF) with or without intracytoplasmic sperm injection (ICSI) for severe male factor; embryo transfer; preimplantation genetic testing in selected cases
• Surgery: hysteroscopic removal of septum, polyps, submucosal fibroids, or adhesions; laparoscopic treatment of endometriosis; varicocele repair; sperm retrieval
• Donor eggs, sperm, or embryos; gestational carrier; fertility preservation (egg or sperm freezing) before cancer treatment

Listed in priority order.

1. Recognize OHSS (after stimulation, especially after hCG trigger or early pregnancy)
   • Abdominal pain and distension, nausea, rapid weight gain (more than about 1 kg / 2 lb per day), decreased urine output, dyspnea
   • Severe: ascites, pleural effusion, hemoconcentration, thrombosis, kidney injury
   • Monitor daily weight, abdominal girth, intake and output, hematocrit and electrolytes; avoid pelvic exams and intercourse (enlarged, fragile ovaries); VTE prophylaxis per order
2. Procedure safety
   • HSG: ask about iodinated contrast allergy and possible pregnancy; an NSAID before the test reduces cramping; after the test expect mild cramping and spotting for 1–2 days; report fever, severe pain, or foul discharge (pelvic infection). Clients with prior PID or dilated tubes (hydrosalpinx) may receive prophylactic antibiotics (e.g., doxycycline) as ordered
   • Oocyte retrieval: bleeding, infection, anesthesia recovery
3. Medication teaching and safety — correct injection technique, timing, storage; report visual symptoms (clomiphene)
4. Psychosocial care
   • Infertility causes grief, guilt, anxiety, relationship strain, and financial stress
   • Use open-ended questions (e.g., "Can you tell me about the stress you are feeling during treatment?"), active listening; avoid false reassurance and blaming either partner
   • Refer to counseling and support groups; respect cultural and religious values about assisted reproduction

• Fertile window: intercourse every 1–2 days around ovulation; LH kits can help time it; avoid oil-based lubricants that may harm sperm
• Semen collection instructions (abstinence 2–7 days, no lubricant, deliver within 1 hour at body temperature)
• Timing of tests in the cycle (HSG after menses and before ovulation; progesterone in mid-luteal phase)
• Multiple pregnancy risk with ovulation induction and how it is reduced (monitoring, single-embryo transfer)
• OHSS warning signs — call promptly for weight gain, decreased urine, abdominal swelling, or shortness of breath
• Men: avoid testosterone and anabolic steroids, hot tubs, smoking; sperm production takes about 2–3 months, so lifestyle changes take time to show

• Evaluate after 12 months (under 35) or 6 months (35 and older); immediately if over 40 or a known cause
• Female age is the strongest predictor of fertility; evaluate both partners
• PCOS → chronic anovulation; hyperprolactinemia suppresses GnRH → anovulation
• Tubal factor — PID (chlamydia, gonorrhea), prior ectopic, surgery, endometriosis
• Asherman syndrome = intrauterine adhesions; POI causes include Turner syndrome
• Male: impaired spermatogenesis most common; Kallmann syndrome = GnRH deficiency; exogenous testosterone suppresses sperm production
• Antisperm antibodies impair motility and fertilization
• Ovulation: mid-luteal progesterone (about 7 days after ovulation); ovarian reserve: AMH, antral follicle count
• HSG after menses, before ovulation; report fever or foul discharge afterward
• Letrozole first-line for PCOS; clomiphene — report visual changes
• OHSS: rapid weight gain, oliguria, ascites — daily weight, girth, I&O