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

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

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.

Study Overview

• Status: Completed
• Conditions: Infertility, Female, Associated With Anovulation
• Intervention / Treatment: Drug: clomiphene citrate; Drug: Saline cervical flushing; Biological: Intrauterine Autologous platelet-rich plasma

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Alkalubia
    • Banha, Alkalubia, Egypt, 13511
      • Banha Faculty Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Clomiphene citrate only; 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; 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.; Other Names: Clomiphene; Drug: Saline cervical flushing; Cervical irrigation with 1 ml of 0.9% normal saline will be done at cycle day 8 and 10 to convince patient-blinded procedure.; Other Names: Saline
Experimental: Platelet-rich plasma plus Clomiphene; 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; 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.; Other Names: Clomiphene; Biological: Intrauterine Autologous platelet-rich plasma; 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.; Other Names: Platelet-rich plasma

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Benha University
• Investigators: Principal Investigator: Ahmed Walid A Morad, Banha Faculty of Medicine, Banha Univerisity

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2018
• Primary Completion (Actual): January 1, 2019
• Study Completion (Actual): January 1, 2020

Study Registration Dates

• First Submitted: December 6, 2018
• First Submitted That Met QC Criteria: December 6, 2018
• First Posted (Actual): December 10, 2018

Study Record Updates

• Last Update Posted (Actual): April 29, 2020
• Last Update Submitted That Met QC Criteria: April 28, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Infertility; Infertility, Female; Anovulation; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Estrogen Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Clomiphene; Enclomiphene; Zuclomiphene
• Other Study ID Numbers: 181210

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No