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

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.

Conditions

• Polycystic Ovary Syndrome

Interventions

DRUG

Progesterone Vaginal Gel 8%

progesterone supplementation for luteal phase support administered with vaginal applicators and used instead of progesterone intramuscular injections or progesterone vaginal suppositories.

DRUG

Letrozole Oral Tablet

letrozole oral tablet 2.5 mg or 5 mg administered cycle day 3-7 for ovulation induction

DIAGNOSTIC_TEST

pelvic ultrasound

pelvic ultrasound performed at cycle day 11 or 12 and repeated as necessary until leading follicle size is \>17 mm in diameter

DRUG

Ovidrel 250 MCG Per 0.5 ML Prefilled Syringe

ovidrel 250 mcg given when leading follicle size is \> 17 mm in diameter

OTHER

Intrauterine insemination or timed intercourse

Intrauterine insemination or timed intercourse (depending on semen parameters) performed 36-40 hours after Ovidrel

Sponsors & Collaborators

• Watson Pharmaceuticals

  collaborator INDUSTRY

• Eastern Virginia Medical School

  lead OTHER

Principal Investigators

• Laurel A Stadtmauer, MD, PhD · Eastern Virginia Medical School

Study Design

Allocation

RANDOMIZED

Purpose

OTHER

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

20 Years

Max Age

40 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2012-07-06

Primary Completion

2016-11-02

Completion

2017-12-30

FDA Drug

Yes

Countries

• United States

Study Locations