Clinical trial NCT03134482: Comparison of Clinical Outcomes Between IVM and Minimal Stimulation IVF in Patients With PCOS
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: No Condition
Keywords: in vitro maturation (IVM)
polycystic ovarian syndrome (PCOS)
ovarian hyperstimulation syndrome (OHSS)
assisted reproductive technology (ART)
Lead sponsor: CHA University
Sponsor class: OTHER
First posted: 2017-05-01
Enrollment: 240
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 39
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Clinical pregnancy rate
timeFrame: At 6 weeks of pregnancy
Secondary outcomes:
measure: Incidence rate of Ovarian hyperstimulation syndrome (OHSS)
timeFrame: Until three weeks later after hCG injection
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: CHA Fertility Center, Seoul station
city: Seoul
country: Korea, Republic of
facility: CHA Gangnam medical center
Study officials:
affiliation: Fertility center of CHA Gangnam medical center, CHA university
name: You Shin Kim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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. doi: 10.1016/j.fertnstert.2004.11.044.
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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. doi: 10.1093/humrep/15.1.165.
citation: 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.
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(11):CD008720. doi: 10.1002/14651858.CD008720.pub2.
citation: 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.