Paraskevi Vogiatzi

In Vitro Maturation in Women with vs. without Polycystic Ovarian Syndrome: A Systematic Review and Meta-Analysis.

Objective To evaluate in vitro maturation (IVM) in sub-fertile women with polycystic ovarian syndrome (PCOS) undergoing in vitro fertilisation (IVF), by comparing outcomes with a control group of non-PCOS. Study design A search strategy was developed for PubMed and studies reporting rates of the following outcomes (live birth; clinical pregnancy; implantation; cycle cancellation; oocyte maturation; oocyte fertilization; miscarriage) between patients with PCOS, PCO and controls undergoing IVM were deemed eligible. The review was conducted in accordance to the PRISMA guidelines and included studies quality was assessed through the Newcastle-Ottawa Quality scale. ORs with their corresponding 95% CIs were calculated for the main analysis and subgroup analyses were performed for PCOS cases vs. controls and PCOS vs. PCO cases. Alternative analyses were performed for live birth and clinical pregnancy, based on cycles and on women. Subgroup analyses for FSH stimulation, hCG priming and type of procedure (IVF/ICSI) were undertaken for all meta-analyses encompassing at least four study arms. Random effects models were used to calculate pooled effect estimates. Results Eleven studies were identified. A total of 268 PCOS patients (328 cycles), 100 PCO patients (110 cycles) and 440 controls (480 cycles) were included in the meta-analysis. A borderline trend towards higher birth rates among PCOS patients emerged (pooled OR = 1.74, 95%CI: 0.99–3.04) mainly reflected at the subgroup analysis vs. controls. Clinical pregnancy (pooled OR = 2.37, 95%CI: 1.53–3.68) and implantation rates (pooled OR = 1.73, 95%CI: 1.06–2.81) were higher, while cancellation rates lower (pooled OR = 0.18, 95%CI: 0.06-0.47) among PCOS vs. non-PCOS subjects; maturation and miscarriage rates did not differ between groups, while a borderline trend towards lower fertilization rates among PCOS patients was observed. Conclusion The present meta-analysis provides preliminary evidence on the effectiveness of IVM as a treatment option when offered in sub-fertile PCOS women, as the latter present at least as high outcome rates as those in non-PCOS.

Potential Pathophysiological Mechanisms of the Beneficial Role of Endometrial Injury in In Vitro Fertilization Outcome.

Successful embryo implantation is a complex process that involves multiple biological mechanisms and reciprocal interactions between the embryo and the proliferated endometrium. In this review, we provide an informative contribution on the pathways underlying the beneficial nature of endometrial injury toward improving implantation rates of embryos conceived and through in vitro fertilization. The evidence published to date are in favor of inducing local endometrial injury in the preceding cycle of ovarian stimulation to improve pregnancy outcomes in women with unexplained and recurrent implantation failure. Endometrial injury triggers a series of biological responses but the findings suggest that no particular pathway is solely adequate to explain the association between trauma and improved pregnancy rates rather than a cluster of events in response to trauma which benefits embryo implantation in ways both known and unknown to the scientific community.

Reactive oxygen species in the follicular fluid of subfertile women undergoing In Vitro Fertilization: A short narrative review

Reactive Oxygen Species (ROS) are produced as a normal product of aerobic metabolism. Naturally, there is an array of protective mechanisms that neutralize ROS, while any potential imbalance between ROS and antioxidants results in oxidative stress. In an In Vitro Fertilization (IVF) setting, existing literature suggests a favorable outcome in terms of oocyte quality/maturation and fertilization rate with increased ROS levels, while other study groups have presented significant data on the detrimental effect of increased ROS concentration in the quality of embryos exposed and their potential to advance. In this study, we examine the conflicting views of the role of ROS in fertilization and embryo quality, especially through their concentration in the follicular fluid of subfertile women undergoing IVF. The current debate could possibly be attributed to the different assay methods and end-point outcomes employed by each research group, along with the noted limited number of the relevant studies published on the subject. Properly conducted studies can further validate and elicit the exact role of ROS as well as their association to female reproduction, and especially to women undergoing IVF.

Granulocyte macrophage colony stimulating factor supplementation in culture media for subfertile women undergoing assisted reproduction technologies: a systematic review.

Granulocyte macrophage colony stimulating factor (GM-CSF) is a cytokine/growth factor produced by epithelial cells that exerts embryotrophic effects during the early stages of embryo development. We performed a systematic review, and six studies that were performed in humans undergoing assisted reproduction technologies (ART) were located. We wanted to evaluate if embryo culture media supplementation with GM-CSF could improve success rates. As the type of studies and the outcome parameters investigated were heterogeneous, we decided not to perform a meta-analysis. Most of them had a trend favoring the supplementation with GM-CSF, when outcomes were measured in terms of increased percentage of good-quality embryos reaching the blastocyst stage, improved hatching initiation and number of cells in the blastocyst, and reduction of cell death. However, no statistically significant differences were found in implantation and pregnancy rates in all apart from one large multicenter trial, which reported favorable outcomes, in terms of implantation and live birth rates. We propose properly conducted and adequately powered randomized controlled trials (RCTs) to further validate and extrapolate the current findings with the live birth rate to be the primary outcome measure.

Hemizona Assay and Sperm Penetration Assay in the Prediction of IVF Outcome: A Systematic Review

The limited predictive value of semen analysis in achieving natural conception or in IVF outcome confirms the need for sperm function tests to determine optimal management. We reviewed HZA and SPA predictive power in IVF outcome, with statistical significance of diagnostic power of the assays. HZA was readily efficient in predicting IVF outcome, while evident inconsistency among the studies analysed framed the SPAs role in male fertility evaluation. Considerable variation was noted in the diagnostic accuracy values of SPA with wide sensitivity (52–100%), specificity (0–100%), and PPV (18–100%) and NPV (0–100%) together with fluctuation and notable differentiation in methodology and cutoff values employed by each group. HZA methodology was overall consistent with minor variation in cutoff values and oocyte source, while data analysis reported strong correlation between HZA results with IVF outcome, high sensitivity (75–100%), good specificity (57–100%), and high PPV (79–100%) and NPV (68–100%). HZA correlated well with IVF outcome and demonstrated better sensitivity/specificity and positive/negative predictive power. Males with normal or slightly abnormal semen profiles could benefit by this intervention and could be evaluated prior to referral to assisted reproduction. HZA should be used in a sequential fashion with semen analysis and potentially other bioassays in an IVF setting.

Mild versus conventional antagonist ovarian stimulation protocols in expected normal responders undergoing IVF/ICSI: a case–control study

Abstract Mild controlled ovarian hyperstimulation (COH) protocols combining clomiphene citrate (CC) or letrozole with gonadotropins were introduced as an effective alternative of conventional COH in normal responders undergoing IVF/ICSI. In this case–control study, we compared 41 participants treated with a mild stimulation protocol receiving gonadotropins combined with either CC (n = 24) or letrozole (n = 17) with 71 subfertile participants with matching baseline characteristics, conforming with the same inclusion criteria and treated with a conventional antagonist protocol. Live birth was determined in reduced rates in the study group compared to the control group, reaching marginal statistical significance [4/41 versus 19/71, p = 0.050], as also in the respective number of clinical pregnancies [6/41 versus 22/71, p = 0.054], although the incidence of miscarriage was similar for both groups [2/41 versus 5/71, p = 0.714]. Most of the secondary parameters examined, favored the conventional antagonist protocol. There was no difference in any of the outcomes reported between the three different stimulation groups in post-hoc analysis. Mild stimulation regimens with the aid of either CC or letrozole employing GnRH antagonists do not seem to constitute an equally effective method as compared to the conventional antagonist protocol to be offered in good prognosis subfertile women seeking an induced cycle toward IVF/ICSI.

Oocyte-triggering day progesterone levels and endometrial appearance in normoresponders undergoing IVF/ICSI cycles: a hypothesis and a study protocol

Abstract In this report, we propose a study protocol capable of improving IVF outcomes in subfertile women with expected normal ovarian response. This proposal derives from conflicting published data and observations in our daily practice, concerning the negative impact of progesterone (P4) elevation at the day of oocyte triggering on pregnancy outcomes. Our hypothesis points to the combination of two previous “suspects” of reduced success after assisted reproduction techniques (ART) – the endometrium ultrasonographic parameters and P4 elevation at the day of oocyte triggering on their impact on pregnancy outcomes. Up-to-the minute data show that, there is a different impact of elevated P4 in fresh, frozen and donor cycles, whereas there are plenty of reports pointing to a different endometrial gene expression on different P4 measurements. Gaps in the literature are linked with a variation of the measurements of P4, its cycle-to-cycle reproducibility, the different cut-off levels used, the impact of various protocols of ovarian stimulation and the limitations of systematic reviews originating from the initial studies. Our hypothesis states that the combination of P4 values and endometrial ultrasound parameters at the day of oocyte triggering can affect clinical pregnancy rates in normal responders undergoing ART.

Transvaginal ovarian trauma, poor responders and improvement of success rates in IVF: Anecdotal data and a hypothesis

In this report, we propose an intervention capable of improving IVF outcomes in subfertile women with poor ovarian response. This intervention derives from anecdotal data and observations in our daily practice, but most importantly from trials on experimental models and subfertile women with Polycystic Ovarian Syndrome (PCOS). Our hypothesis suggests that transvaginal induction of trauma to the ovary in the cycle preceding IVF should benefit poor ovarian responders and their lowered pregnancy rates by increasing - at least - the number of retrieved oocytes during oocyte retrieval. Up-to-the minute data show that, via this means, there is a unique response of the ovarian surface epithelium and stroma to the induced trauma. The potential pathways of this beneficial response involve an improvement of the raised gonadotrophins to act either through the mechanical reduction of the size of the ovary or through alterations of the hormonal profile by lowering LH, inhibin and local androgen concentrations through hypothalamic-pituitary axis feedbacks, the induction of increased blood flow to the ovaries, a differentiated local immune reaction and a non-elucidated as yet role of reactive oxygen species. In this report, we also describe the technique and the associated possible negative points while we try to point out the needed research steps to ensure its efficiency before it enters daily clinical practice.