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Meta-Analysis
. 2018 Nov 15;11(11):CD006606.
doi: 10.1002/14651858.CD006606.pub4.

In vitro maturation in subfertile women with polycystic ovarian syndrome undergoing assisted reproduction

Charalampos S Siristatidis  1 , Abha Maheshwari, Dennis Vaidakis, Siladitya Bhattacharya
Affiliations
Meta-Analysis

In vitro maturation in subfertile women with polycystic ovarian syndrome undergoing assisted reproduction

Charalampos S Siristatidis et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: Polycystic ovarian syndrome (PCOS) occurs in 4% to 7% of all women of reproductive age and 50% of women presenting with subfertility. Subfertility affects 15% to 20% of couples trying to conceive. A significant proportion of these women ultimately need assisted reproductive technology (ART). In vitro fertilisation (IVF) is one of the assisted reproduction techniques employed to raise the chances of achieving a pregnancy. For the standard IVF technique, stimulating follicle development and growth before oocyte retrieval is essential, for which a large number of different methods combining gonadotrophins with a gonadotrophin-releasing hormone (GnRH) agonist or antagonist are used. In women with PCOS, the supra-physiological doses of gonadotrophins used for controlled ovarian hyperstimulation (COH) often result in an exaggerated ovarian response, characterised by the development of a large cohort of follicles of uneven quality, retrieval of immature oocytes, and increased risk of ovarian hyperstimulation syndrome (OHSS). A potentially effective intervention for women with PCOS-related subfertility involves earlier retrieval of immature oocytes at the germinal-vesicle stage followed by in vitro maturation (IVM). So far, the only data available have derived from observational studies and non-randomised clinical trials.

Objectives: To assess the effectiveness and safety of IVM followed by IVF or ICSI versus conventional IVF or ICSI among women with PCOS undergoing assisted reproduction.

Search methods: This is the second update of this review. We performed the search on 17 April 2018.The search was designed with the help of the Cochrane Gynaecology and Fertility Group Information Specialist, for all published and unpublished randomised controlled trials (RCTs).We searched the the Cochrane Gynaecology and Fertility Group Specialised Register of controlled trials, CENTRAL via the Cochrane Central Register of Studies Online, MEDLINE, Embase, CINAHL, and the trial registers for ongoing and registered trials and the Open Grey database for grey literature from Europe. We made further searches in the National Institute for Health and Care Excellence (NICE) fertility assessment and treatment guidelines. We handsearched reference lists of relevant systematic reviews and RCTs, together with PubMed and Google for any recent trials that have not yet been indexed in the major databases.

Selection criteria: All RCTs on the intention to perform IVM before IVF or ICSI compared with conventional IVF or ICSI for subfertile women with PCOS, irrespective of language and country of origin.

Data collection and analysis: Two review authors independently selected studies, assessed risk of bias, extracted data from studies, and attempted to contact the authors of studies for which data were missing. Our primary outcomes were live birth per woman randomised and miscarriage. We performed statistical analysis using Review Manager 5. We assessed evidence quality using GRADE methods.

Main results: We found two RCTs suitable for inclusion in the review and six ongoing trials that have not yet reported results. Both included studies were published as abstracts in international conferences.Both studies were at unclear or high risk of bias for most of the seven domains assessed. Common problems were unclear reporting of study methods and lack of blinding. The main limitations in the overall quality of the evidence were high risk of bias and serious imprecision.There were no data on the primary outcomes of this review, namely live birth per woman randomised and miscarriage.Both studies reported clinical pregnancy rate: there was evidence of an effect between IVM and IVF, favouring the former (odds ratio 3.10, 95% confidence interval 1.06 to 9.00; 71 participants; 2 studies; I2 = 0%; very low-quality evidence). The incidence of OHSS was zero in both studies in both groups.There were no data for the other outcomes specified in this review.

Authors' conclusions: Though promising data on the in vitro maturation (IVM) technique have been published, unfortunately there is still no evidence from properly conducted randomised controlled trials upon which to base any practice recommendations regarding IVM before in vitro fertilisation (IVF) or intracytoplasmic sperm injection for women with polycystic ovarian syndrome. Regarding our secondary outcomes, very low-quality evidence showed that clinical pregnancy was higher with IVM when compared to IVF, whereas the incidence of ovarian hyperstimulation syndrome was zero in both studies in both groups. We are awaiting the results of six ongoing trials and eagerly anticipate further evidence from good-quality trials in the field.

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Conflict of interest statement

Charalampos S Siristatidis: no conflicts of interest to disclose.

Abha Maheshwari: no conflicts of interest to disclose.

Dennis Vaidakis: no conflicts of interest to disclose.

Siladitya Bhattacharya: no conflicts of interest to disclose.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Forest plot of comparison: 1 IVM versus IVF, outcome: 1.1 Clinical pregnancy.
See this image and copyright information in PMC

Update of

References

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References to ongoing studies

ISRCTN61229302 {published data only}
    1. ISRCTN61229302. A multicentre randomised controlled trial comparing in vitro maturation of oocytes with in vitro fertilisation in women with an increased risk of ovarian hyperstimulation syndrome [Comparing in vitro maturation of oocytes with in vitro fertilisation in women with an increased risk of ovarian hyperstimulation syndrome: A multicentre randomised controlled trial with non‐randomised pilot study]. http://www.isrctn.com/ISRCTN61229302 (first received 27 May 2010). [DOI: 10.1186/ISRCTN61229302] - DOI
NCT00867763 {published data only}
    1. NCT00867763. In vitro maturation with in vitro fertilization (IVF) compared to mild in vitro fertilization (IVM vs IVF) [Clinical Research Study on in Vitro Maturation With IVF Compared to Mild Stimulation IVF]. http://clinicaltrials.gov/show/NCT00867763 (first received March 24, 2009).
NCT01473459 {published data only}
    1. NCT01473459. Comparison between two fertility protocols in obese polycystic ovary syndrome patients [Comparison Between Two Fertility Protocols in Obese Polycystic Ovary Syndrome]. clinicaltrials.gov/show/NCT01473459 (first received November 17, 2011). [ClinicalTrials.gov Identifier:NCT01473459]
NCT03134482 {published data only}
    1. NCT03134482. Comparison of Clinical Outcomes Between IVM and Minimal Stimulation IVF in Patients With PCOS [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]. ClinicalTrials.gov/show/NCT03134482 (first received May 1, 2017). [https://www.clinicaltrials.gov/ct2https://clinicaltrials.gov/ct2/show/re...
NCT03405701 {published data only}
    1. NCT03405701. IVM Versus IVF in High Antral Follicle Count Patients [The Effectiveness and Safety of in Vitro Maturation of Oocytes Versus in Vitro Fertilization in Women With High Antral Follicle Count (AFC): a Randomised Controlled Trial]. clinicaltrials.gov/show/NCT03405701 (first received January 23, 2018). [https://www.clinicaltriClinicalTrials.gov Identifier: NCT03405701]
NCT03463772 {published data only}
    1. NCT03463772. IVM versus standard in vitro fertilization in infertile patients diagnosed with PCOS [In Vitro Maturation Versus Standard in Vitro Fertilization in Infertile Patients Diagnosed With Polycystic Ovaries Syndrome: a Study Protocol for a Single‐center Prospective, Randomized Controlled Clinical Trial]. ClinicalTrials.gov/show/NCT03463772 (first reveived March 13, 2018). [ClinicalTrials.gov Identifier: NCT03463772]

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References to other published versions of this review

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