Autologous Platelet-rich Plasma for Clomiphene Citrate-induced Thin Endometrium

Study Overview
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Brief Summary
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This is a prospective self-controlled clinical study. Women with clomiphene Citrate failure with thin endometrium less than 7 millimeters for at least 3 cycles will be selected (N = 30). Patients will receive 2 ovarian stimulation cycles with Clomiphene citrate (CC) 100 mg/ day for 5 days from cycle day 3. A control cycle (CC only cycle) woman will continue on CC alone plus cervical irrigation of cervix with 1 ml of 0.9% normal saline at cycle day 8 and 10 to assure patient-blinded method. The study group, the same will be done plus the intrauterine infusion of Autologous platelet-rich plasma (PRP) in 8th and 10th days of the cycle. In both groups, the endometrial thickness and Power Doppler evaluation of their endometrial and sub-endometrial blood flow will be measured on the day of Human Chorionic Gonadotropin (HCG) administration.

Detailed Description
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This is a pilot prospective self-controlled clinical trial. Women with Clomiphene Citrate failure with documented thin endometrium less than 7 millimeters for at least 3 stimulation cycles will be chosen (N = 30). Patients will experience 2 ovarian stimulation cycles with Clomiphene citrate (CC) in a dose of 100 mg/ day for 5 days starting from cycle day 3. A control cycle (CC only cycle) woman will continue on Clomiphene Citrate alone plus cervical irrigation of cervix with 1 ml of 0.9% normal saline at cycle day 8 and 10 to confirm patient-blinded process. The study group, the same will be done in addition to the intrauterine infusion of with Autologous platelet-rich plasma (PRP) in 8th and 10th days of the cycle. In both groups, the endometrial thickness and Power Doppler evaluation of their endometrial and sub-endometrial blood flow will be measured on the day of HCG administration.

Official Title
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Intrauterine Infusion of Autologous Platelet-rich Plasma to Prevent a Thin Endometrium in Infertile Women Undergoing Clomiphene Citrate Therapy: a Pilot Prospective Self-controlled Trial

Conditions
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Infertility, Female, Associated With Anovulation

Intervention / Treatment
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* Drug: clomiphene citrate
* Drug: Saline cervical flushing
* Biological: Intrauterine Autologous platelet-rich plasma


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women with clomiphene citrate failure (defined as at least previous 3 ovulatory cycles with clomiphene citrate, with no pregnancy), persistently thin endometrium (less than 7 millimeters in at least 3 cycles). normal baseline Follicle Stimulating Hormone, Luteinizing Hormone, and free testosterone levels, patent tubes by hysterosalpingography, and satisfactory male semen analysis Exclusion Criteria: previous ovarian surgery; endocrine disorders ; pelvic pathologies; chronic hepatic, cardiovascular, or renal disease; other factors of infertility and use of gonadotropins or hormonal contraception through the latest 6 months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 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: Non-Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Clomiphene citrate only<br>Infertile women (30 women) with prior clomiphene citrate failure (ovulation was documented without conception), with thin endometrium (<7mm) in at least 3 cycles. Saline cervical flushing will be done at cycle day 8 and 10 to convince patient-blinded procedure. | Drug: clomiphene citrate<br>* Clomiphene citrate-only arm: Patients will receive Clomiphene citrate induction (in a dose of 100 mg/day starting from day 3 of the cycle for 5 days). Sonographic assessment of endometrial thickness together with Power Doppler evaluation endometrial and sub-endometrial blood flow a will be done in the Day of HCG injection.<br>* Other names: Clomiphene;Drug: Saline cervical flushing<br>* Cervical irrigation with 1 ml of 0.9% normal saline will be done at cycle day 8 and 10 to convince patient-blinded procedure.<br>* Other names: Saline;|
| Experimental: Platelet-rich plasma plus Clomiphene<br>Women who did not conceive on the Clomiphene citrate-only cycle will receive Clomiphene citrate 100 mg/ day starting from the third day of the cycle. Intrauterine Autologous platelet-rich plasma will be done on the cycle days 8 and 10. | Drug: clomiphene citrate<br>* Clomiphene citrate-only arm: Patients will receive Clomiphene citrate induction (in a dose of 100 mg/day starting from day 3 of the cycle for 5 days). Sonographic assessment of endometrial thickness together with Power Doppler evaluation endometrial and sub-endometrial blood flow a will be done in the Day of HCG injection.<br>* Other names: Clomiphene;Biological: Intrauterine Autologous platelet-rich plasma<br>* Under complete aseptic cares and ultrasound supervision, Autologous platelet-rich plasma (0.5 - 1 ml) was immediately injected into the uterine cavity using an intrauterine insemination catheter in the cycle days 8 and 10. The Autologous platelet-rich plasma is prepared in collaboration with the Department of Clinical Pathology, Faculty of Medicine, Benha University.<br>* Other names: Platelet-rich plasma;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endometrial thickness | Transvaginal sonographic estimation of maximal distance traversing endometrial- myometrial interphase on each endometrial stripe in a -midsagittal plane in the uterine fundus. | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Power Doppler estimation of endometrial and sub-endometrial vascularity | Endometrial and sub-endometrial vascularity signals will be evaluated using the power Doppler. | 1 day | 
| Clinical pregnancy rate | Recognizing pregnancy through positive urinary HCG test plus sonographic detection of cardiac pulsations | At the end of a 28-day menstrual cycle. |