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

No Condition Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03134482
• Other study ID #: Chau
• Status: Recruiting
• Phase: N/A
• Start date: May 1, 2017
• Est. completion date: December 31, 2023

Study information

• Verified date: March 2020
• Source: CHA University
• Contact: You Shin Kim, MD, PhD
• Phone: 82-2-2002-0303
• Email: medikys[@]cha.ac.kr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 20 Years to 39 Years

Eligibility

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

Related Conditions & MeSH terms

• No Condition
• Polycystic Ovary Syndrome

Intervention

Procedure:
• IVM
No gonadotropin is used, but hCG priming is utilized 36 hour before oocyte maturation.
• 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.

Locations

Country	Name	City	State
Korea, Republic of	CHA Fertility Center, Seoul station	Seoul
Korea, Republic of	CHA Gangnam medical center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
CHA University

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (8)

Aboulghar MA, Mansour RT. Ovarian hyperstimulation syndrome: classifications and critical analysis of preventive measures. Hum Reprod Update. 2003 May-Jun;9(3):275-89. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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:CD008720. Review. — View Citation

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. Review. Update in: Cochrane Database Syst Rev. 2018 Nov 15;11:CD006606. — View Citation

Söderström-Anttila V, Mäkinen 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. Epub 2005 Feb 3. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical pregnancy rate	Clinical pregnancy was determined by observation of a gestational sac with fetal heart beat by transvaginal ultrasound scan.	At 6 weeks of pregnancy
Secondary	Incidence rate of Ovarian hyperstimulation syndrome (OHSS)	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