A Phase 2/3 interventional study of Progesterone Vaginal Gel 8% and Letrozole Oral Tablet in Polycystic Ovary Syndrome, sponsored by Eastern Virginia Medical School. Completed at 1 site in United States. Open to female participants aged 20 Years to 40 Years. Per ClinicalTrials.gov, last updated 2018-02-26.
Sponsored by Eastern Virginia Medical School · Phase 2/3, Interventional, and Other
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.
Approval of the study was obtained from the local IRB. Prospective volunteers had had an infertility workup including blood hormone levels (FSH, LH, E2, Progesterone, Prolactin, and Thyroid), partner's semen analysis, HSG, laparoscopy or hydrosonogram, plus a baseline evaluation including ultrasound of ovaries and uterus performed as standard of care. If the results of these tests and the remaining Inclusion/Exclusion criteria were met, the study consent was reviewed with participants and signatures were obtained. Participants contacted the clinic at the start of their menses (spontaneous or progesterone-induced) to start the treatment cycle. Eligibility criteria was reviewed, and Letrozole 2.5-7.5 mg day 3-7 was initiated based on BMI and prior response. An ultrasound was performed on cycle day 11 or 12 and repeated if needed to determine response until at least 1 follicle with mean diameter > 17mm in size was observed. When the appropriate follicle size was reached, participants were randomized into one of the two treatment groups as determined by a randomization table, and Ovidrel (250mcg) was administered. If there was no response identified by follicle growth on day 21, the participant was considered a letrozole failure, the cycle was stopped, and the participant was dropped from the study and was not included in subsequent cycles.
IUI/TI was performed at 24-48 hours after the Ovidrel (hCG) injection. If the participant was randomized to progesterone (Crinone), the luteal phase was supplemented once daily with vaginal progesterone (Crinone 8%) starting the second day after the IUI or TI and continued for 14 days. A urine or serum pregnancy test was performed as standard of care 16 days after the IUI/TI. If the test was positive, a confirmatory blood level (βhCG) was performed as standard of care X2 (1 week apart) and an ultrasound on post-hCG day 35-42 was done. Any pregnancies occurring in either treatment group were followed for delivery outcomes. Information regarding the delivery (induced, vaginal, cesarean section), date of birth, infant measurements (weight and length) and other important information regarding the infant's condition was obtained. Participants were allowed to undergo up to 3 cycles of letrozole as the pregnancy rates for the first 3 cycles have been shown to be similar. The participants were re-randomized each cycle. If the participant was pregnant, Crinone (8%) was continued until 10 weeks gestation in both groups.
Each participant was able to proceed with up to 3 cycles (consecutively, if desired) of OI over the next 6 months and was re-randomized each cycle.
956 studies on the registry are indexed under Polycystic Ovary Syndrome; 176 are open to participants now.
This study's enrollment of 52 is below the median of 70 across 697 interventional studies indexed under Polycystic Ovary Syndrome.
Browse Polycystic Ovary Syndrome studies →Eastern Virginia Medical School is the lead sponsor of 56 studies on the registry; 8 are open to participants now.
Of its 9 completed or terminated interventional studies of FDA-regulated products, 1 (11%) have results posted.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
Drug: Letrozole Oral Tablet · Diagnostic Test: pelvic ultrasound · Drug: Ovidrel 250 MCG Per 0.5 ML Prefilled Syringe · Other: Intrauterine insemination or timed intercourse
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.
Drug: Progesterone Vaginal Gel 8% · Drug: Letrozole Oral Tablet · Diagnostic Test: pelvic ultrasound · Drug: Ovidrel 250 MCG Per 0.5 ML Prefilled Syringe · Other: Intrauterine insemination or timed intercourse
progesterone supplementation for luteal phase support administered with vaginal applicators and used instead of progesterone intramuscular injections or progesterone vaginal suppositories.
Also known as: Crinone 8% vaginal gel
letrozole oral tablet 2.5 mg or 5 mg administered cycle day 3-7 for ovulation induction
pelvic ultrasound performed at cycle day 11 or 12 and repeated as necessary until leading follicle size is \>17 mm in diameter
ovidrel 250 mcg given when leading follicle size is \> 17 mm in diameter
Also known as: recombinant hCG 250 mcg
Intrauterine insemination or timed intercourse (depending on semen parameters) performed 36-40 hours after Ovidrel
Clinical pregnancy rates
The primary endpoint of the trial is the Clinical Pregnancy Rate per cycle initiated
Time frame: Per initiated cycle of treatment. At the end of Cycle 1, 2, and 3 (each cycle is 28 days) and if pregnant up to 8 weeks after completion of cycle
Live birth rates
The secondary endpoint is the Live Birth Rate per cycle initiated (each cycle is 28 days)
Time frame: Up to 1 year or until delivery
Plan to share: No
Ran from Jul 2012 to primary completion in Nov 2016, 51 months.
Of 13 phase 2/3 interventional studies under Polycystic Ovary Syndrome, half reached primary completion within 12 months of starting (the median); a quarter within 8 and three quarters within 26. This study's 51 months is above that.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Feb 2018. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Progesterone
Eastern Virginia Medical School