Clinical trial · Interventional
Vaginal Progesterone Supplementation in Women With PCOS Undergoing Ovulation Induction With Letrozole
"Supplementation of the Luteal Phase With Vaginal Progesterone (Crinone 8%) in Women With Polycystic Ovary Syndrome Undergoing Ovulation Induction With Letrozole: A Prospective and Randomized Controlled Trial
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Polycystic Ovary Syndrome | — | UNRESOLVED | — |
Interventions
Interventions (5)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Intrauterine insemination or timed intercourse | Other | — | UNRESOLVED |
| Letrozole Oral Tablet | Drug | Letrozole | ALIAS |
| Ovidrel 250 MCG Per 0.5 ML Prefilled Syringe | Drug | — | UNRESOLVED |
| pelvic ultrasound | Diagnostic Test | — | UNRESOLVED |
| Progesterone Vaginal Gel 8% | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (2)
- type
- OTHER
- label
- # 1- no progesterone therapy
- description
- Letrrozole 2.5 to 5 mg oral tablet cycle day 3-7.Pelvic ultrasound at cycle day 11 or 12 and repeat if needed until leading follicle is \>17 mm. Ovidrel 250 mcg injected sq. Timed intercourse or intrauterine insemination. No supplemental progesterone therapy in luteal phase
- interventionNames
- Drug: Letrozole Oral Tablet
- Diagnostic Test: pelvic ultrasound
- Drug: Ovidrel 250 MCG Per 0.5 ML Prefilled Syringe
- Other: Intrauterine insemination or timed intercourse
- type
- ACTIVE_COMPARATOR
- label
- # 2 - Progesterone Vaginal Gel 8%
- description
- Letrrozole 2.5 to 5 mg oral tablet cycle day 3-7. Pelvic ultrasound at cycle day 11 or 12 and repeat if needed until leading follicle is \>17 mm. Ovidrel 250 mcg injected sq. Timed intercourse or intrauterine insemination.Crinone 8% (progesterone) vaginal therapy was provided in luteal phase for 14 days .Administration was started the second day after intrauterine insemination or timed intercourse.
- interventionNames
Eligibility
Eligibility (as posted)
- Sex
- Female
- Minimum age
- 20 Years
- Maximum age
- 40 Years
Show eligibility criteria text
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
References
Publications (12)
- BACKGROUNDFranks S. Assessment and management of anovulatory infertility in polycystic ovary syndrome. Endocrinol Metab Clin North Am. 2003 Sep;32(3):639-51. doi: 10.1016/s0889-8529(03)00044-6. PMID 14560891
- BACKGROUNDGOLDZIEHER JW, GREEN JA. The polycystic ovary. I. Clinical and histologic features. J Clin Endocrinol Metab. 1962 Mar;22:325-38. doi: 10.1210/jcem-22-3-325. No abstract available. PMID 13899931
- BACKGROUNDRichardson MR. Current perspectives in polycystic ovary syndrome. Am Fam Physician. 2003 Aug 15;68(4):697-704. PMID 12952386
- BACKGROUNDHamilton-Fairley D, Taylor A. Anovulation. BMJ. 2003 Sep 6;327(7414):546-9. doi: 10.1136/bmj.327.7414.546. No abstract available. PMID 12958117
- BACKGROUNDVendola KA, Zhou J, Adesanya OO, Weil SJ, Bondy CA. Androgens stimulate early stages of follicular growth in the primate ovary. J Clin Invest. 1998 Jun 15;101(12):2622-9. doi: 10.1172/JCI2081. PMID 9637695
- BACKGROUNDRotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004 Jan;81(1):19-25. doi: 10.1016/j.fertnstert.2003.10.004. PMID 14711538
- BACKGROUNDGanesh A, Goswami SK, Chattopadhyay R, Chaudhury K, Chakravarty B. Comparison of letrozole with continuous gonadotropins and clomiphene-gonadotropin combination for ovulation induction in 1387 PCOS women after clomiphene citrate failure: a randomized prospective clinical trial. J Assist Reprod Genet. 2009 Jan;26(1):19-24. doi: 10.1007/s10815-008-9284-4. Epub 2009 Jan 7. PMID 19127427
- BACKGROUNDCasper RF. Aromatase inhibitors in ovarian stimulation. J Steroid Biochem Mol Biol. 2007 Aug-Sep;106(1-5):71-5. doi: 10.1016/j.jsbmb.2007.05.025. Epub 2007 May 24.