Table 4.
Medications to Treat Infertilitya
| Example | Dose | Adverse effects (rate) | Efficacy |
|---|---|---|---|
| Selective estrogen receptor modifiers, used for ovulation induction | |||
| Clomiphene citrate | 50 mg/daily orally × 5 d (starting between cycle days 2 and 5 after an induced or spontaneous bleed); may increase up to 150 mg/daily if ovulation does not occurb; identification of an ovulatory LH surge for timing of intercourse or IUI can be done using urinary LH kits or office estradiol/ultrasound | Hot flashes (33%), headache (34%), fatigue (14%), dizziness (7%), irritability (21%); thin endometrium (15%−50%49); visual disturbances (2%); multiple pregnancy (up to 12.5%)45 | 24%−31% Cumulative LBR over 3 cycles when combined with IUI for unexplained infertility8; 19.1% LBR over 5 cycles in women with PCOS46 |
| Aromatase inhibitors, used for ovulation induction (off-label indication) | |||
| Letrozole | 2.5 mg/daily orally × 5d (starting between cycle days 2 and 5 after an induced or spontaneous bleed); may increase up to 7.5 mg/daily if ovulation does not occur; monitoring for ovulation as with clomiphene citrate | Hot flashes (20.3%), headache (41%), fatigue (21.7%), dizziness (12.3%), irritability (18%); multiple pregnancy (up to 14.3%)50 In contrast to clomiphene, letrozole does not appear to adversely affect endometrial thickness and cervical mucus50 |
27.5% Cumulative LBR over 5 cycles in women with PCOS46 |
| Gonadotropins, used for ovarian stimulation in combination with timed intercourse/IUI or IVF | |||
| Follicle-stimulating hormone: urinary FSH (Bravelle) recombinant follitropin beta (Follistim); recombinant follitropin alpha (Gonal-F) | For ovarian hyperstimulation with timed intercourse or IUI: typical starting dose is 37.5–75 IU/d; for IVF, typical starting dose is 150–200 IU/d | Injection site reaction (10%), abdominal bloating/discomfort (27%−34%); ovarian hyperstimulation syndrome (1%−5% of cycles)51; multiple pregnancy (up to 36%)52 | 32%−33% Cumulative LBR over 4 cycles when used in combination with IUI for ovarian stimulation; depending on age, LBR may be >65% per cycle when used for IVF with autologous oocytes8 |
| LH: recombinant luteotropin alpha (Luveris) | |||
| Human menopausal gonadotropin: Menopur, Repronex | |||
| Human chorionic gonadotropin (hCG), used as an ovulatory trigger in ovulation induction and ovarian hyperstimulation cycles | |||
| Recombinant hCG (Ovidrel) | 250-μg Recombinant hCG | Injection site swelling, pain, erythema (10%−20%) | Based on OI or OS regimen used |
| Urinary hCG (Pregnyl, Novarel) | 5000–10 000 Units of urinary hCG | ||
| GnRH agonists, used for pituitary downregulation and as an ovulatory trigger during ovarian hyperstimulation cycles | |||
| Leuprolide acetate (Lupron) | Injection: 0.5–1 mg subcutaneous daily | Short-term menopausal symptoms (eg, hot flashes, mood swings, vaginal dryness, headache) (70%−80%) | Based on OI or OS regimen used |
| Nafarelin acetate (Synarel) | Nasalspray: 400 μg twice daily | ||
| GnRH antagonists, used for pituitary downregulation during ovarian hyperstimulation cycles | |||
| Ganirelix; Cetrorelix acetate (Cetrotide) | Injection: 0.25 mg daily | Similar to GnRH agonists | Based on OI or OS regimen used |
| Pulsatile GnRH therapy, used for ovulation induction in patients with hypothalamic amenorrhea | |||
| GnRH therapy | 75 ng/kg (Discontinued after ovulation) | Injection site adverse effects; multiple gestation (4%−8%53); ovarian hyperstimulation (<1%54) | Pregnancy rates 70%−100% after up to 6 mo48 |
| Dopamine agonists, for treatment of hyperprolactinemic anovulation (titrated to normalize serum prolactin levels) c | |||
| Bromocriptine (Parlodel) | Starting at 1.25mg orally daily | Dizziness (25%), headache (25%−30%), nausea/vomiting (30%−50%) | 52%−72% Resumption of ovulatory cycles55 |
| Cabergoline (Dostinex) | Starting at 0.25 mg orally twice weekly; may be given vaginally to minimize adverse effects | ||
| Progesterone | |||
| Crinone 8% vaginal gel | Gel: 90 mg intravaginal daily | Abdominal discomfort (15%), headache (13%), vaginal discharge (7%), nausea (22%) | |
| Endometrin, 100-mg vaginal tablet | Tablet: 100 mg intravaginal 2–3 times daily | ||
| Intramuscular progesterone in oil | Injection: 50 mg daily | ||
Abbreviations: GnRH, gonadotropin-releasing hormone; IUI, intrauterine insemination; IVF, in vitro fertilization; LBR, live birth rate; LH, luteinizing hormone; OI, ovulation induction; OS, ovarian stimulation; PCOS, polycystic ovary syndrome.
a
The medications may be used alone or in combination in a fertility treatment cycle.
b
Higher doses (200–250 mg daily have been used in women refractory to these doses, but these doses exceed US Food and Drug Administration recommendation.
c
Not available in the US.