Effect of Progestin-Induced Withdrawal Bleed on Ovulation Induction Cycles With Clomiphene Citrate

Study Overview
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Brief Summary
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Women with polycystic ovary syndrome (PCOS) can suffer from infertility because they do not produce an egg each month, resulting in irregular periods. As a result, these women often need a medication called clomiphene citrate (clomiphene) to induce ovulation. A traditional 'clomiphene protocol' begins with a short course of progestin treatment to bring on a period (termed a 'withdrawal bleed') before starting the clomiphene medication. Newer evidence, however, has suggested that this progestin-induced shedding of the uterine lining (i.e., withdrawal bleed) may decrease the chances of pregnancy. The purpose of our study is to determine whether withdrawal bleeding has an impact on pregnancy rates for patients with PCOS undergoing a clomiphene cycle. It is hypothesized that patients who undergo ovulation induction with clomiphene citrate without prior endometrial shedding will have higher clinical pregnancy rates than those who begin with a progestin-induced withdrawal bleed.

Official Title
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Effect of Progestin-Induced Endometrial Shedding on Ovulation Induction Cycles With Clomiphene Citrate: A Randomized Study

Conditions
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Polycystic Ovary Syndrome, Infertility

Intervention / Treatment
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* Drug: Progestin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Polycystic ovary syndrome (Rotterdam 2003 Consensus Criteria) and a diagnosis of anovulatory infertility Age 18-38 years At least 1 patent fallopian tube (as demonstrated by hysterosalpingogram, hydrotubation or hysterosonogram within the last year) Normal semen analysis (total motile sperm count >20million/ml) Normal uterine cavity (as demonstrated by hysterosalpingogram, hydrotubation or hysterosonogram within the last year) Undergoing ovulation-induction with clomiphene citrate without intra-uterine insemination (IUI) Exclusion Criteria: Body mass index (BMI) < 17 kg/m2 or > 40 kg/m2 Prior treatment with clomiphene citrate Presence of a hydrosalpinx (as seen on ultrasound, hysterosalpingogram, hydrotubation or hysterosonogram) Those with systemic disease such as diabetes mellitus, uncontrolled thyroid disease, systemic lupus erythematosus and antiphospholipid antibody syndrome Any other cause of infertility other than anovulation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 38 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: No withdrawal bleed<br>No progestin prior to ovulation induction with clomiphene citrate | Drug: Progestin<br>* The experimental group will have no progestin prior to ovulation induction with clomiphene citrate, while the comparison group will have progestin medication prior to ovulation induction with clomiphene citrate, as per usual care.<br>* Other names: medroxyprogesterone acetate (MPA), i.e. Provera;|
| No Intervention: Withdrawal Bleed<br>Progestin prior to beginning ovulation induction with clomiphene citrate (standard care) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical pregnancy rate per ovulation | clinical pregnancy rate (gestational sac seen on ultrasound approximately 6-7 weeks after starting clomiphene) per ovulation | 6 weeks after starting clomiphene | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cumulative pregnancy rate | cumulative pregnancy rate | assessed 9 months after the ovulation induction cycles | 
| ovulation rate | ovulation rate (progesterone >10nmol/L per clomiphene cycle) | assessed 1 month after each induced ovulation cycle | 
| ongoing pregnancy rate | ongoing pregnancy rate (pregnancy with a fetal heartbeat >12 weeks gestational age) | assessed 12 weeks after clinical pregnancy is acheived | 
| miscarriage rate | miscarriage rate | Assessed 4 months after clinical pregnancy acheived | 
| multiple pregnancy rate | multiple pregnancy rate (twins and higher order multiples) | Assessed 4 months after clinical pregnancy acheived | 
| endometrial thickness | endometrial thickness (assessed via transvaginal ultrasound) | Assessed at 1 month after conception | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Polycystic ovary syndrome, Progestin, Endometrial shedding, Ovulation induction cycles, Clomiphene citrate, Clinical pregnancy rate