Comparison of Clinical Outcomes Between IVM and Minimal Stimulation IVF in Patients With PCOS

March 23, 2020 updated by: You Shin Kim, CHA University

Comparison of Clinical Outcomes Between in Vitro Maturation and Minimal Stimulation in Vitro Fertilization in Patients With Polycystic Ovarian Syndrome; Prospective, Randomized Controlled, Parallel, Open-label, Clinical Trial

Polycystic ovarian syndrome (PCOS) is most common endocrinologic disease in women of reproductive age with incidence of 6.6 ~ 8%. About fifty percent of the patients with PCOS manifest subfertility and significant proportion of these woman need assisted reproductive technology (ART). These patients are very sensitive to gonadotropins during conventional in vitro fertilization (IVF) and the risk of ovarian hyperstimulation syndrome (OHSS) is high. In vitro maturation (IVM) is an emerging alternative option to conventional IVF for minimizing the risk of OHSS in patients with PCOS. Until now, several studies has been reported the favorable outcomes of oocyte maturation rate, fertilization rate, clinical pregnancy rate, and live birth rate during IVM procedure. However, these results were from retrospective or observational study and there was no suitable randomized controlled trial (RCT).

Therefore, this prospective RCT is aimed to compare and analyze the clinical outcomes between IVM and minimal stimulation IVF in women with PCOS, assessing if IVM is recommendable clinical practice or not.

Study Overview

Status

Recruiting

Conditions

Detailed Description

Polycystic ovarian syndrome (PCOS) is most common endocrinologic disease in women of reproductive age with incidence of 6.6 ~ 8%. About fifty percent of the patients with PCOS manifest subfertility and significant proportion of these women need assisted reproductive technology (ART). These patients are very sensitive to gonadotropins during conventional in vitro fertilization (IVF) and the risk of ovarian hyperstimulation syndrome (OHSS), an iatrogenic complication, is very high.

In vitro maturation (IVM) is has been suggested as an alternative option to conventional IVF for eliminating the risk of OHSS in patients with PCOS. In 1994, Trounson et al succeeded in fertilization of in vitro matured oocytes and transferring embryo during unstimulated IVF procedure in women with PCOS. Since then IVM was developed as one method of ART field.

Previously it had been reported that maturation rate of oocytes retrieved from patients with PCOS were lower than oocytes from women without PCOS. However, in several observational studies, maturation rate of oocytes was up to 80.3%, fertilization was up to 21.9%~50% per cycle, and live birth rated was 15.9% per retrieval and 33% per cycle. And in several retrospective case-control studies of comparing IVM and conventional IVF, the miscarriage rate and ectopic pregnancy rate were similar, whereas the maturation rate of oocyte was up to 84%, fertilization rate was 43~70% and pregnancy rate was 22~56%. Because ovarian stimulation is not utilized, OHSS risk is preventable and cost is effective in IVM procedure.

Generally there are three types of IVM techniques; firstly, gonadotropin priming, in which technique small amount of gonadotropin is used for 3 to 5 days. Secondly, human chorionic gonadotropin (hCG) priming, in which hCG is used before oocyte retrieval. Thirdly, no gonadotropin and hCG priming is used. In gonadotropin-priming IVM technique, it had been reported that the number of retrieved oocytes were increased and pregnancy rate was improved from 0 to 29%, but there was no clear evidence of the efficacy. hCG priming technique, most commonly used technique, is for promoting meiotic resumption before full maturation of oocyte. The maturation rate of oocytes was 69~84%, fertilization rate 45 ~ 80%, pregnancy rate 31 ~ 38.5% and live birth rate was 33% in the studies of investigating hCG priming IVM technique in women with PCOS.

Summarizing these observational and retrospective studies, it is expectable that IVM is promising ART method in patients with PCOS, minimizing the risk of OHSS with improved clinical pregnancy rate. However, there was no suitable randomized controlled trial (RCT) to confirm whether IVM is recommendable primary clinical ART practice to women with PCOS.

Therefore, this prospective RCT is aimed to compare and analyze the clinical outcomes between hCG-primed IVM protocol and minimal stimulation IVF with Gonadotropin-releasing hormone (GnRH) antagonist protocol in women with PCOS in fresh cycles.

Study Type

Interventional

Enrollment (Anticipated)

240

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

      • Seoul, Korea, Republic of, 04367
        • Recruiting
        • CHA Fertility Center, Seoul station
        • Contact:
      • Seoul, Korea, Republic of, 06135
        • Recruiting
        • CHA Gangnam Medical Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 39 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Women diagnosed with PCOS under age of 40 years (PCOS diagnosis is based on Revised 2003 Rotterdam criteria of PCOS)

Exclusion Criteria:

  • severe male factor subfertility requiring testicular sperm extraction (TESE) or oligoasthenoteratozoospermia
  • couples requiring preimplantation genetic screening or diagnosis
  • women had undergone ovarian stimulation 30 days before assisted reproductive technology (ART)
  • women with severe endometriosis or dysfunctional uterine bleeding
  • women with severe uterine factor subfertility (ex. submucosal myoma, intramural myoma protruding endometrium, severe intrauterine adhesion, etc)
  • women with ovarian malignancy
  • women with severe tubal factor subfertility (ex. persistent hydrosalpinx even after surgery)
  • women had undergone treatment of malignancy 5 years before screening of this trial
  • women with history of thromboembolism
  • women with age of 40 years or more
  • women with stimulation dose over 150 IU of exogenous FSH

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: In vitro maturation (IVM)

hCG primed in vitro maturation (IVM) procedure Gonadotropin is not used in this patient group If the endometrial thickness in 6mm or more and the mean diameter of largest follicle is 11 mm or less on menstrual cycle day 9 to 12 on ultrasonography, oocyte retrieval is planned two days later.

Recombinant hCG injection (priming) is given 36 hour before oocyte retrieval, followed by intracytoplasmic sperm injection (ICSI) for oocyte fertilization.

The biochemical pregnancy is confirmed by serum beta hCG 15 days later oocyte retrieval.

The clinical pregnancy is confirmed when gestational sac is detected by transvaginal ultrasonography 3 weeks later oocyte retrieval.

No gonadotropin is used, but hCG priming is utilized 36 hour before oocyte maturation.
Active Comparator: Minimal stimulation IVF

minimal stimulation IVF procedure These patients are stimulated with 150 or less IU of recombinant Follicle-stimulating hormone (FSH) from menstrual cycle day 3 in GnRH antagonist protocol.

If the mean diameters of two or more follicles are 17mm or more, oocyte retrieval is planned two days later.

Recombinant hCG is triggered 36 hour before oocyte retrieval, followed by intracytoplasmic sperm injection (ICSI) for oocyte fertilization if needed.

The biochemical pregnancy is confirmed by serum beta hCG 14 days later oocyte retrieval.

The clinical pregnancy is confirmed when gestational sac is detected by transvaginal ultrasonography 3 weeks later oocyte retrieval.

IVF with minimal use of gonadotropin, i.e. 150 or less IU of recombinant FSH, followed by hCG triggering in GnRH antagonist protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical pregnancy rate
Time Frame: At 6 weeks of pregnancy
Clinical pregnancy was determined by observation of a gestational sac with fetal heart beat by transvaginal ultrasound scan.
At 6 weeks of pregnancy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence rate of Ovarian hyperstimulation syndrome (OHSS)
Time Frame: Until three weeks later after hCG injection
OHSS rate in each arm. Patients' symptoms (abdominal distension, bloating and pain, nausea, vomiting, palpitation) and ultrasonographic findings (fluid collection in pelvic and abdominal cavity, enlarged ovarian size) are investigated for OHSS detection.
Until three weeks later after hCG injection

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Principal Investigator: You Shin Kim, MD, PhD, Fertility center of CHA Gangnam medical center, CHA university

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2017

Primary Completion (Anticipated)

December 31, 2022

Study Completion (Anticipated)

December 31, 2023

Study Registration Dates

First Submitted

April 11, 2017

First Submitted That Met QC Criteria

April 28, 2017

First Posted (Actual)

May 1, 2017

Study Record Updates

Last Update Posted (Actual)

March 24, 2020

Last Update Submitted That Met QC Criteria

March 23, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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