P-661 Therapeutic management in women with a diminished ovarian reserve (DOR): a systematic review and meta-analysis of randomized control trials
Authors: Castaldo E , Alviggi C , Campitiello M R , Ubaldi F M , Rienzi L , Vaiarelli A , Cimadomo D , Strina I , Buonfantino C , Vigilante L , Cariati F , Ilardi B , D’Hooghe T , Esteves S C , Conforti A 
Published: June 2023

Abstract

Study question
Unlike previous reviews, our meta-analysis investigated protocols involving only women with diminished ovarian reserve (DOR) identified by antral follicle count and/or AMH (POSEIDON criteria).

Summary answer
Testosterone, GH and delayed antagonist starting protocol are associated with better IVF outcomes comparing with respective control groups.

What is known already
The clinical management of women with diminished ovarian reserve (DOR) is a challenge in the field of medically assisted reproduction. Several therapeutic strategies have been proposed, however, with mixed results. This issue is probably linked to the fact that the definition of diminished ovarian reserve used was inconsistent among trials. The POSEIDON criteria define women with DOR, based on antral follicle count and levels of antimullerian hormone (AFC &lt;5 or AMH &lt;1.2 ng/ml).

Study design, size, duration
We conducted a systematic search using the MEDLINE, EMBASE, and ISI WEB OF KNOWLEDGE, to identify relevant studies published up to July 2022. The reference lists were also hand-searched to implement the systematic search. We selected only RCTs in which the study population was affected by DOR with basal levels of AMH and AFC consistent with Poseidon criteria. The primary outcome was live birth rate or ongoing pregnancy when data on live birth was unavailable.

Participants/materials, setting, methods
A total of 14,386 articles were identified through the search, and duplications were removed using the EndNote library and manually (n = 6,945). The titles and abstracts of 7,441 articles were scrutinized, and 117 full-text articles were assessed for eligibility. In total, forty-seven RCTs were included. The following interventions were evaluated: DHEA, testosterone; GH high versus low gonadotropin dose regimen, delayed started protocol, letrozole, clomiphene citrate, luteal phase stimulation, dual triggering, LH supplementation, corifollitropin alfa.

Main results and the role of chance
Testosterone, high-dose gonadotropin regimen, and delayed antagonist starting protocol significantly improved the total number of eggs collected. In addition, GH and delayed starting protocol significantly increased the number of metaphase II oocytes. Testosterone, GH, and delayed antagonist starting protocol were associated with improved clinical pregnancy rates among all interventions evaluated. Testosterone and GH were also associated with higher live birth rates comparing with no supplemented women.

Limitations, reasons for caution
The main limitation of the present review relates to the minimal number of studies reporting live birth rates. Another relevant issue is the heterogeneity in women involved and the IVF protocols' diversity. More trials are demanding to corroborate our findings.

Wider implications of the findings
Our study's results might help clinicians to identify the most appropriate approach to managing women with DOR. Furthermore, our findings may stimulate researchers to develop more specific trials centred on specific categories of low-prognosis women, for example, those with a standardized diagnosis of DOR.

Trial registration number
The review protocol was registered at http://www.crd.york.ac.uk/PROSPERO/ (registration number CRD42022346117O).