Comparison of Ovulation Induction Cycle Outcomes Between Early and Late Dose Increments for Low Dose Gonadotropin Step-up Protocol Among Infertile Women Diagnosed With Polycystic Ovary Syndrome: Prospective Randomised Trial

Low dose gonadotropin step-up ovulation induction treatment is the universally accepted and utilized teratment protocol for infertile women diagnosed with polycystic ovary syndrome (PCOS). First dose increment is advised on 14th day of ovarian stimulation with gonadotropins to decrease multiple follicle generation and cycle cancellation rates. However, clinicians impatiently increase gonadotropin dose on 7th day of stimulation without strong scientific evidence. This randomised controlled study will be the first study which will compare safety and ovulation induction cyle outcomes of early and late dose increments among infertile women diagnosed with PCOS.

Study Overview

• Status: Unknown
• Conditions: Polycystic Ovary Syndrome; Infertility, Female
• Intervention / Treatment: Drug: Gonadotropin dose increment timing

Detailed Description

Low dose gonadotropin step-up ovulation induction treatment is the universally accepted and utilized teratment protocol for infertile women diagnosed with polycystic ovary syndrome. First dose increment is advised on 14th day of ovarian stimulation with gonadotropins to decrease multiple follicle generation and cycle cancellation rates. However, clinicians impatiently increase gonadotropin dose on 7th day of stimulation without strong scientific evidence. This randomised controlled study will be the first study which will compare safety and ovulation induction cyle outcomes of early and late dose increments among infertile women diagnosed with polycystic ovary syndrome.

We will start low dose step-up ovulation induction treatment by using 50 IU recombinant FSH for 21-39 years old non- obese patients (BMI <30 kg/m2) diagnosed with PCOS and . We will perform folliculometry on 7th day of ovulation induction. In case of absence for at least one >10 mm dominant follicle, we will randomise these women by using blind envelope selection method for assignment of early or late dose incerement groups. Half of the patients will receive 25 IU dose increment on 7th day of ovulation induction, remaining half will receive dose increment on 14th day of ovulation induction. We will continue ovarian stimulation without any other dose increment until 35th day of stimulation as deadline time restriction. We will perform folliculometry and serum estradiol measurement intermittently during ovulation induction. We will record ovulation induction cycle outcomes and clinical pregnancy results of the study group following finalization for treatment cyle of each patient. We will compare ovulation induction cycle outcomes of these two dose increment groups.

• Study Type: Interventional
• Enrollment (Anticipated): 160
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Serkan Kahyaoglu, M.D; Phone Number: +905058868040; Email: serkan.kahyaoglu@sbu.edu.tr

Study Locations

• Turkey
  • Ankara, Turkey
    • Recruiting
    • University of Health Sciences, Ankara City Hospital, Department of Reproductive Endocrinology
    • Contact: Serkan Kahyaoglu, M.D; Phone Number: +905058868040; Email: serkan.kahyaoglu@sbu.edu.tr
    • Principal Investigator: Serkan Kahyaoglu, M.D
    • Sub-Investigator: Inci Kahyaoglu, M.D
    • Sub-Investigator: Omer H Yumusak, M.D
    • Sub-Investigator: Berna Seckin, M.D
    • Sub-Investigator: Hacer C Gulerman, M.D
    • Sub-Investigator: Muzeyyen G Ozaksit, M.D
    • Sub-Investigator: Ozlem Moraloglu Tekin, M.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 39 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:Infertile women who have been diagnosed with PCOS based on Rotterdam criteriae and who have not succeeded to get pregnant by using oral ovulation induction agents and whose BMI levels are <30 kg/m2 will be included to the study.

Exclusion Criteria:Infertile women with tubal diseases, male factor infertility, endometriosis, previous pelvic surgery history, chronic systemic disease, BMI levels>30 kg/m2 and who are not voluntary to attend to the study will be excluded from the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Early dose increment; Patients who have received 25 IU gonadotropin dose increment on 7th day of ovulation induction	Drug: Gonadotropin dose increment timing; Gonadotropin dose increments of 25 IU will be utilized on 7th and 14th day of ovulation induction for each study group.
Active Comparator: Late dose increment; Patients who have received 25 IU gonadotropin dose increment on 14th day of ovulation induction	Drug: Gonadotropin dose increment timing; Gonadotropin dose increments of 25 IU will be utilized on 7th and 14th day of ovulation induction for each study group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of preovulatory follicles	Number of >14 mm sized follicles at the end of the ovulation induction treatment	35 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biochemical pregnancy rate	Serum pregnancy test will be performed 2 weeks after ovulation triggering	2 weeks after ovulation triggering
Clinical pregnancy rate	Clinical pregnancy rate which will be evaluated 3 weeks after ovulation triggering	3 weeks after ovulation triggering
Cycle length in days	Total number of ovulation induction days until ovulation triggering	7-35 days
Cycle cancellation	Cycle cancellation due to >=3 preovulatory follicles (>14 mm in size) at the end of the ovulation induction treatment	35 days
Multiple pregnancy rate	Multiple pregnancy rate which will be evaluated 3 weeks after ovulation triggering	3 weeks after ovulation triggering

Collaborators and Investigators

• Sponsor: Saglik Bilimleri Universitesi
• Investigators: Principal Investigator: Serkan Kahyaoglu, M.D, Ankara City Hospital, Department of Reproductive Endocrinology

Publications and helpful links

Helpful Links

• Improved monofollicular ovulation in anovulatory or oligo-ovulatory women after a low-dose step-up protocol with weekly increments of 25 international units of follicle-stimulating hormone
• Pilot study of the optimal protocol of low dose step-up follicle stimulating hormone therapy for infertile women
• Ovulation induction with a starting dose of 50 IU of recombinant follicle stimulating hormone in WHO group II anovulatory women: the IO-50 study, a prospective, observational, multicentre, open trial

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2020
• Primary Completion (Actual): August 20, 2020
• Study Completion (Anticipated): August 20, 2022

Study Registration Dates

• First Submitted: August 24, 2020
• First Submitted That Met QC Criteria: August 24, 2020
• First Posted (Actual): August 27, 2020

Study Record Updates

• Last Update Posted (Actual): August 27, 2020
• Last Update Submitted That Met QC Criteria: August 24, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Infertility; Polycystic ovary syndrome; Ovulation induction; Gonadotropin; Low dose step-up
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Endocrine System Diseases; Disease; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Polycystic Ovary Syndrome; Syndrome; Infertility; Infertility, Female
• Other Study ID Numbers: E1-20-377

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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