Vaginal Progesterone Supplementation in Women With PCOS Undergoing Ovulation Induction With Letrozole

• Status: Completed
• Trial end date: 2017-12-30
• Target enrollment: 0
• Participant gender: Female

Summary

Aromatase inhibitors such as letrozole are hypothesized to maintain normal hypothalamic/ pituitary feedback mechanisms and in the case of OI (ovulation induction) in women with PCOS, may act to increase follicular sensitivity to FSH by increasing intrafollicular androgen levels. Letrozole also may act to increase midluteal P levels presumably by induction of follicles and corpora lutea. The investigators are asking the question whether P supplementation with Crinone (8%) may have an additive beneficial effect on endometrial development in those women taking letrozole. Progesterone levels in the endometrium (tissue levels) have been documented to be significantly higher than serum levels after vaginal administration which may lead to higher pregnancy rates. In addition P has been shown to decrease LH pulse frequency which is elevated in PCOS and has been shown to down regulate endometrial androgen receptors. There have been retrospective studies showing progesterone supplementation seems to benefit both CC and letrozole treatment groups. In fact, this study showed the only pregnancies in the letrozole group were those in women who took P supplementation. However the number of cycles studied was small. There is a place for a randomized controlled trial (RCT) to determine if luteal phase P supplementation with Crinone should be used in all women using letrozole for Ovulation Induction (OI) in combination with Intrauterine Insemination (IUI) or Timed Intercourse (TI). This is currently not done in all clinical practices.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Eastern Virginia Medical School
• Collaborator: Watson Pharmaceuticals
• Treatments: Chorionic Gonadotropin; Letrozole; Progesterone

Criteria

Inclusion Criteria:

• Women who have anovulatory or oligoovulatory infertility who are undergoing ovulation induction for infertility with TI or IUI , with or without regular cycles defined as cycle length > 35 days, < 26 days or amenorrhea (no cycles in the past six months), and who meet 2 out of 3 of the Rotterdam Criteria (1. Chronic anovulation or irregular cycles, 2. Clinical or biochemical hyperandrogenism, 3. Polycystic appearing ovaries on ultrasound.)

• Day 3 FSH(Follicle stimulating hormone)< 10 (obtained within 2 years prior to screening

• Documented infertility for at least 1 year or documented anovulation

• Willing to participate in up to 3 cycles of OI with letrozole and IUI or TI

• Partner's or donor's SA> 5 million motile sperm within 2 years of screening

• Patients may have received clomiphene citrate or letrozole treatment in the past.

Exclusion Criteria:

• Untreated thyroid or prolactin abnormalities

• Pregnancy in the last 3 months

• BMI< 18 or >40kg/m2

• Abnormal uterine bleeding of undetermined origin

• Contraindications to pregnancy

• Progesterone sensitivity

• Uterine anomalies seen on ultrasound (performed within 6 months prior to screening) that can affect pregnancy chances such as submucosal uterine fibroids or polyps

• Three or more previous consecutive pregnancy losses

• Blocked fallopian tubes X2 (documented by HSG, laparoscopy, or hydrosonogram completed within past 3 years)

• More than 3 failed monitored letrozole cycles prior to enrolling