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Mild Stimulation Protocol Using Clomiphene Citrate for Women With PCOS Undergoing in Vitro Fertilization

A

American University of Beirut Medical Center

Status and phase

Active, not recruiting
Phase 4

Conditions

PCO - Polycystic Ovaries
Infertility

Treatments

Drug: mild stimulation protocol: oral Clomiphene Citrate
Drug: Conventional Stimulation Protocol: will receive FSH/HMG

Study type

Interventional

Funder types

Other

Identifiers

NCT04157725
AmericanUBMC-MS

Details and patient eligibility

About

Infertility is of increasing significance affecting almost 48.5 million couples around the world. Anovulation is a major cause of infertility in women with polycystic ovary syndrome (PCOS) accounting for about 80% of women with anovulatory infertility. Ultrasound morphological features of PCOS include the presence of 16 or more follicles measuring 2-9 mm in diameter, and/or an overall large ovarian volume of >10mm3. Women with PCOS ultrasound features exhibit an exaggerated response to controlled ovarian stimulation.

Controlled ovarian hyperstimulation is an established prerequisite to assisted reproductive techniques with the aim of obtaining a higher yield of oocytes and ultimately increasing success rates. According to the ESHRE/ASRM consensus on infertility treatment related to polycystic ovary syndrome, IVF seems to represent a reasonable treatment option as the risks of multiple pregnancies and ovarian hyper-stimulation syndrome may be kept to a minimum. The optimal stimulation protocol however is still debatable. Recently, patient-friendly stimulation protocols for assisted reproductive technology were introduced aiming at minimizing overall treatment costs and health hazards to the patient. Mild stimulation protocols are considered relatively novel protocols. They consist of combining oral stimulation agents (clomiphene citrate or letrozole) with low-dose gonadotropins as effective alternatives to conventional gonadotropin-only stimulation protocols. Mild stimulation protocol has been associated with better tolerance, ease of use, and comparable livebirth outcomes. The investigators aim to test the hypothesis that mild stimulation protocols could produce a similar proportion of term livebirths to conventional treatment, while reducing treatment costs and health hazards.

This is a prospective non-randomized controlled trial comparing a mild ovarian stimulation protocol to conventional treatment for assisted reproductive technology at the Division of Reproductive Endocrinology and Infertility - Haifa Idriss Fertility Center - American University of Beirut Medical Center.

Full description

Infertility is a medical condition of increasing significance with an estimated 48.5 million affected couples around the world . Anovulation is a major cause of infertility in women with polycystic ovary syndrome (PCOS) accounting for about 80% of women with anovulatory infertility. The prevalence of PCOS varies widely among different ethnic populations and is highest in the Middle East. One way to diagnose PCOS is on the basis of the Rotterdam criteria, according to which women should satisfy 2 of 3 criteria including anovulation, polycystic ovarian morphology on ultrasound and hyperandrogenism (either clinical or biochemical). Trans-vaginal ultrasound evaluation is an important tool to assess ovarian features and determine the risk for ovarian hyper-response to follicle stimulation.

Ultrasound morphological features of polycystic ovary syndrome (PCOS) include the presence of 16 or more follicles measuring 2-9mm in diameter, and/or an overall large ovarian volume of >10mm3. Women with PCOS ultrasound features exhibit an exaggerated response to controlled ovarian stimulation . It was demonstrated that the number of baseline follicles seen on ultrasound strongly correlates with the number of recovered oocytes, and that was especially documented in women with a baseline number of pre-antral follicles exceeding 15 who were found to be at increased risk for ovarian hyper-stimulation syndrome .

Controlled ovarian hyperstimulation is an established prerequisite to assisted reproductive techniques with the aim of obtaining a higher yield of oocytes and ultimately increasing success rates. According to the ESHRE/ASRM consensus on infertility treatment related to polycystic ovary syndrome (2008), IVF seems to represent a reasonable treatment option as the risks of multiple pregnancies and ovarian hyper-stimulation syndrome may be kept to a minimum. The optimal stimulation protocol however is still debatable.

The investigators plan to conduct a prospective non-randomized controlled trial comparing a mild ovarian stimulation protocol to conventional treatment for assisted reproductive technology at the Division of Reproductive Endocrinology and Infertility - Haifa Idriss Fertility Center - American University of Beirut Medical Center.

Interest in embryo cryopreservation will be discussed with candidates before the start of IVF treatment. Women meeting the inclusion criteria who show no interest in embryo cryopreservation and in obtaining supernumerary embryos will be allocated to the mild stimulation (group A) protocol. Alternatively, women interested in obtaining a high number of embryos for the purpose of cryopreservation will be allocated to the conventional stimulation (group B) protocol.

Enrollment

154 estimated patients

Sex

Female

Ages

18 to 40 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

  • Female patients between 18-40 years of age
  • Antral follicle count exceeding 16 and/or AMH exceeding 3.5 ng/dl
  • PCOS features as per Rotterdam criteria: 2 of 3 criteria: a. Ultrasound morphology; b. Oligo/amenorrhea; c. Hyperandrogenism (clinical or chemical).

Exclusion criteria

  • Recurrent implantation failure
  • Recurrent pregnancy loss
  • Congenital uterine anomalies
  • Untreated maternal medical conditions (Diabetes, thyroid disease...)

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

154 participants in 2 patient groups

Group A (mild stimulation protocol)
Experimental group
Treatment:
Drug: mild stimulation protocol: oral Clomiphene Citrate
Group B (conventional stimulation protocol)
Active Comparator group
Treatment:
Drug: Conventional Stimulation Protocol: will receive FSH/HMG

Trial contacts and locations

1

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Central trial contact

Johnny T Awwad, M.D

Data sourced from clinicaltrials.gov

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