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

NCT ID: NCT03134482

Last Updated: 2020-03-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

240 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-05-01

Study Completion Date

2023-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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No Condition

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

IVM

Intervention Type PROCEDURE

No gonadotropin is used, but hCG priming is utilized 36 hour before oocyte maturation.

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.

Group Type ACTIVE_COMPARATOR

Minimal stimulation IVF

Intervention Type PROCEDURE

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

Interventions

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IVM

No gonadotropin is used, but hCG priming is utilized 36 hour before oocyte maturation.

Intervention Type PROCEDURE

Minimal stimulation IVF

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

Intervention Type PROCEDURE

Eligibility Criteria

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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
Minimum Eligible Age

20 Years

Maximum Eligible Age

39 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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CHA University

OTHER

Sponsor Role lead

Responsible Party

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You Shin Kim

Associate professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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You Shin Kim, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Fertility center of CHA Gangnam medical center, CHA university

Locations

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CHA Fertility Center, Seoul station

Seoul, , South Korea

Site Status RECRUITING

CHA Gangnam medical center

Seoul, , South Korea

Site Status RECRUITING

Countries

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South Korea

Central Contacts

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You Shin Kim, MD, PhD

Role: CONTACT

82-2-2002-0303

Facility Contacts

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You Shin Kim, MD, PhD

Role: primary

2-2-2002-0303

You Shin Kim, MD, PhD

Role: primary

82-2-2002-0303

References

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Siristatidis CS, Vrachnis N, Creatsa M, Maheshwari A, Bhattacharya S. In vitro maturation in subfertile women with polycystic ovarian syndrome undergoing assisted reproduction. Cochrane Database Syst Rev. 2013 Oct 8;(10):CD006606. doi: 10.1002/14651858.CD006606.pub3.

Reference Type BACKGROUND
PMID: 24101529 (View on PubMed)

Cha KY, Chung HM, Lee DR, Kwon H, Chung MK, Park LS, Choi DH, Yoon TK. Obstetric outcome of patients with polycystic ovary syndrome treated by in vitro maturation and in vitro fertilization-embryo transfer. Fertil Steril. 2005 May;83(5):1461-5. doi: 10.1016/j.fertnstert.2004.11.044.

Reference Type BACKGROUND
PMID: 15866585 (View on PubMed)

Choi MH, Lee SH, Kim HO, Cha SH, Kim JY, Yang KM, Song IO, Koong MK, Kang IS, Park CW. Comparison of assisted reproductive technology outcomes in infertile women with polycystic ovary syndrome: In vitro maturation, GnRH agonist, and GnRH antagonist cycles. Clin Exp Reprod Med. 2012 Dec;39(4):166-71. doi: 10.5653/cerm.2012.39.4.166. Epub 2012 Dec 31.

Reference Type BACKGROUND
PMID: 23346527 (View on PubMed)

Child TJ, Phillips SJ, Abdul-Jalil AK, Gulekli B, Tan SL. A comparison of in vitro maturation and in vitro fertilization for women with polycystic ovaries. Obstet Gynecol. 2002 Oct;100(4):665-70. doi: 10.1016/s0029-7844(02)02193-2.

Reference Type BACKGROUND
PMID: 12383531 (View on PubMed)

Chian RC, Buckett WM, Tulandi T, Tan SL. Prospective randomized study of human chorionic gonadotrophin priming before immature oocyte retrieval from unstimulated women with polycystic ovarian syndrome. Hum Reprod. 2000 Jan;15(1):165-70. doi: 10.1093/humrep/15.1.165.

Reference Type BACKGROUND
PMID: 10611207 (View on PubMed)

Soderstrom-Anttila V, Makinen S, Tuuri T, Suikkari AM. Favourable pregnancy results with insemination of in vitro matured oocytes from unstimulated patients. Hum Reprod. 2005 Jun;20(6):1534-40. doi: 10.1093/humrep/deh768. Epub 2005 Feb 3.

Reference Type BACKGROUND
PMID: 15695312 (View on PubMed)

Reavey J, Vincent K, Child T, Granne IE. Human chorionic gonadotrophin priming for fertility treatment with in vitro maturation. Cochrane Database Syst Rev. 2016 Nov 16;11(11):CD008720. doi: 10.1002/14651858.CD008720.pub2.

Reference Type BACKGROUND
PMID: 27852101 (View on PubMed)

Aboulghar MA, Mansour RT. Ovarian hyperstimulation syndrome: classifications and critical analysis of preventive measures. Hum Reprod Update. 2003 May-Jun;9(3):275-89. doi: 10.1093/humupd/dmg018.

Reference Type BACKGROUND
PMID: 12859048 (View on PubMed)

Siristatidis CS, Papapanou M, Maheshwari A, Vaidakis D. In vitro maturation in subfertile women with polycystic ovarian syndrome undergoing assisted reproduction. Cochrane Database Syst Rev. 2025 Feb 6;2(2):CD006606. doi: 10.1002/14651858.CD006606.pub5.

Reference Type DERIVED
PMID: 39912435 (View on PubMed)

Other Identifiers

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Chau

Identifier Type: -

Identifier Source: org_study_id

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