What medications help with female fertility?

Medications for Female Fertility

For anovulatory women with polycystic ovary syndrome (PCOS), clomiphene citrate 50-150 mg/day for 5 days is the first-line medication, inducing ovulation in approximately 70% of patients and achieving pregnancy rates of 44% within three treatment cycles. 1, 2, 3

First-Line Ovulation Induction Agents

Clomiphene Citrate (Preferred Initial Treatment)

• Start with 50 mg daily for 5 days in women with PCOS-related anovulation, as this dose avoids side effects while maintaining efficacy comparable to higher doses 2
• Increase to 100-150 mg daily if ovulation does not occur, with maximum doses up to 200 mg/day inducing ovulation in ~70% of treated patients 2, 3
• Continue for up to 6 treatment cycles before considering alternative therapies, as the largest series demonstrate effectiveness for at least this duration 4
• Achieves ovulation rates with odds ratio of 6.82 (95% CI 3.92-11.85) compared to placebo at standard doses 3
• Results in pregnancy rates of 44% per woman within three cycles 5

Important caveat: Clomiphene may paradoxically impair fertility through adverse effects on cervical mucus and endometrial development despite inducing ovulation 2. If pregnancy does not occur after 3-6 ovulatory cycles, consider switching to gonadotropins rather than continuing clomiphene indefinitely.

Low-Dose FSH (Gonadotropins)

• Consider as first-line treatment in older PCOS patients (approaching age 40) or after clomiphene failure 5
• Start with 50 IU daily and titrate carefully to avoid ovarian hyperstimulation 1, 5
• Achieves superior outcomes compared to clomiphene: pregnancy rate per first cycle 30% vs 14.6% (P=0.003), cumulative pregnancy rate 52.1% vs 41.2% (P=0.021), and live birth rate 52% vs 39% (P=0.04) 5
• Pregnancies occur faster with FSH - 30% conceive in the first cycle versus only 14.6% with clomiphene 5
• More expensive than clomiphene but more effective, particularly for time-sensitive patients 5

Metformin (Alternative for PCOS)

• Administer 1700 mg/day in insulin-resistant PCOS patients 6
• Comparable efficacy to clomiphene with ovulation rates of 55.4% and pregnancy rates of 10.8% per cycle 6
• Cumulative pregnancy rate of 62.9% over 6 months, not significantly different from clomiphene (48.6%, P=0.225) 6
• Particularly useful in PCOS patients with insulin resistance, as metformin improves this metabolic dysfunction 2

Combination Therapies

Clomiphene Plus Gonadotropins

• Combining clomiphene with human menopausal gonadotropin (HMG) has been a standard protocol in assisted reproduction and appears more effective than clomiphene alone 2, 4
• Consider this combination for clomiphene-resistant patients before proceeding to full gonadotropin protocols 2

Adjunctive Medications

• Human chorionic gonadotropin (hCG) may be needed to trigger ovulation in clomiphene cycles when follicles develop but spontaneous ovulation does not occur 2
• Corticosteroids can be combined with clomiphene in specific cases 2

Intrauterine Insemination (IUI) Considerations

• IUI with ovarian stimulation improves pregnancy rates in couples with unexplained infertility or mild male factor 1
• Ovarian stimulation for IUI typically uses clomiphene citrate or gonadotropins 1
• IUI success is limited when total motile sperm count is <5 million after processing; consider proceeding directly to IVF/ICSI in these cases 1

Fertility Preservation Context

Oocyte/Embryo Cryopreservation

• Controlled ovarian stimulation with gonadotropins is the standard approach for fertility preservation before gonadotoxic treatments 1
• Adding tamoxifen or letrozole to stimulation protocols in breast cancer patients reduces estradiol exposure, though benefits remain unclear 1
• Letrozole or tamoxifen combined with gonadotropins achieves adequate oocyte yield with lower estradiol levels compared to standard protocols 1

Critical Warnings

Medications to AVOID

• GnRH agonists during chemotherapy do NOT reliably preserve fertility - conflicting trial results show some studies with higher menstrual recovery rates but no consistent increase in pregnancy rates 1
• Testosterone therapy is absolutely contraindicated in women seeking fertility, as it suppresses ovulation 1

Safety Considerations

• Multiple pregnancy risk increases with all ovulation induction agents, particularly at higher doses 2, 3
• Ovarian hyperstimulation syndrome can occur, especially with gonadotropins 2
• Unsubstantiated concerns about ovarian cancer risk with clomiphene exist but remain controversial 2, 3

Treatment Algorithm

1. Confirm anovulation as the cause of infertility
2. Start clomiphene citrate 50 mg daily for 5 days in women with PCOS or oligo-ovulation 2, 3
3. Increase to 100-150 mg if no ovulation occurs in first cycle 2
4. Continue for 3-6 ovulatory cycles before changing strategy 5, 4
5. Switch to low-dose FSH (50 IU starting dose) if pregnancy does not occur after 3-6 clomiphene cycles, or consider FSH first-line in older patients 5
6. Consider metformin 1700 mg/day as alternative first-line in insulin-resistant PCOS patients 6
7. Proceed to IVF/ICSI if simpler treatments fail after appropriate trials 1