Commercially Available Molecular Approaches to Evaluate Endometrial Receptivity: A Systematic Review and Critical Analysis of the Literature.

Despite the advances in the field of reproductive medicine, implantation failure represents a challenging condition affecting 10-30% of patients subjected to in vitro fertilization (IVF). Research has focused on the identification of molecules playing crucial roles in endometrial receptivity, with the aim of designing predictive tools for efficient detection of the implantation window. To that end, novel molecular genomic and transcriptomic approaches have been introduced as promising tools to enable personalized approaches with the aim of optimizing embryo transfer dating. However, the clinical value of these approaches remains unclear. The aim of this study is to provide a systematic review and critical analysis of the existing evidence regarding the employment of commercially available novel approaches to evaluate endometrial receptivity. An Embase and PubMed/Medline search was performed on 1 February 2022. From the 475 articles yielded, only 27 were included and analyzed. The considerable heterogeneity of the included articles indicates the uniqueness of the implantation window, showcasing that the optimal time for embryo transfer varies significantly between women. Moreover, this study provides information regarding the technical aspects of these advanced molecular tools, as well as an analysis of novel possible biomarkers for endometrial receptivity, providing a basis for future research in the field.

The Current Evidence Regarding COVID-19 and Pregnancy: Where Are We Now and Where Should We Head to Next?

Despite the volume of publications dedicated to unraveling the biological characteristics and clinical manifestations of SARS-CoV-2, available data on pregnant patients are limited. In the current review of literature, we present an overview on the developmental course, complications, and adverse effects of COVID-19 on pregnancy. A comprehensive review of the literature was performed in PubMed/Medline, Embase, and Cochrane Central databases up to June 2021. This article collectively presents what has been so far reported on the identified critical aspects, namely complications during pregnancy, delivery challenges, neonatal health care, potential routes of viral transmission, including vertical transmission or breastfeeding, along with the risks involved in the vaccination strategy during pregnancy. Despite the fact that we are still largely navigating uncharted territory, the observed publication explosion in the field is unprecedented. The overwhelming need for data is undoubtable, and this serves as the driver for the plethora of publications witnessed. Nonetheless, the quality of data sourced is variable. In the midst of the frenzy for reporting on SARS-CoV-2 data, monitoring this informational overload is where we should head to next, considering that poor quality research may in fact hamper our attempts to prevail against this unparalleled pandemic outbreak.

Empty Zona Pellucida Only Case: A Critical Review of the Literature.

The presence of empty zona pellucida (EZP) in oocytes following oocyte retrieval (OR) during an in vitro fertilization (IVF) cycle presents a major clinical and laboratory challenge in assisted reproduction. It has been attributed to several factors such as the ovarian stimulation protocol employed, the damaging of the follicles during oocyte retrieval (OR) mainly through the high aspiration pressure, during the denudation technique, and the degeneration of oolemma within the zona pellucida (ZP) through apoptosis. The role of ZP is pivotal from the early stages of follicular development up to the preimplantation embryo development and embryo hatching. Polymorphisms or alterations on the genes that encode ZP proteins may contribute to EZP. We present a critical review of the published literature hitherto on EZP and available options when encountered with the phenomenon of EZP. Concerning the former, we found that there is rare data on this phenomenon that merits documentation. The latter includes technical, genetic, and pathophysiological perspectives, along with specific treatment options. In conclusion, we identify the lack of a definitive management proposal for couples presenting with this phenomenon, we underline the need for an algorithm, and indicate the questions raised that point towards our goal for a strategy when addressing a previous finding of EZP.

Oocyte and embryo vitrification in the IVF laboratory: a comprehensive review.

Vitrification is an excellent tool in the IVF laboratory, enabling options and offering flexibility in assisted reproduction. The technology of cryopreservation has been underway since the early 20th century. The advent of vitrification has advanced the expectations in routine clinical practice in the IVF laboratory presenting impressive results both in post-thaw survival, and in clinical pregnancy rates, as well as significantly enhancing clinical results on preimplantation genetic diagnosis (PGD). Contradicting opinions have been published recently on the limitations and potential that vitrification has in the laboratory, as well as on the optimal approach to employ vitrification in IVF. This review aims to present a comprehensive analysis of the practical aspects of vitrification including concerns and options regarding its use on oocytes and embryos while comparing it with the traditional "slow-freezing" cryopreservation technique.

Role of gonadotropin-releasing hormone antagonist in the management of subfertile couples with intrauterine insemination and controlled ovarian stimulation.

OBJECTIVE: To assess whether the clinical pregnancy rate of patients treated with recombinant FSH and IUI can be improved by the addition of a GnRH antagonist. DESIGN: Prospective, controlled study. SETTING: Reproductive medicine clinic. PATIENT(S): Ninety-three patients with primary or secondary infertility. INTERVENTION(S): Patients were allocated to controlled ovarian stimulation with recombinant FSH (50-150 IU/d) only (control group, n=45) or to recombinant FSH (50-150 IU/d) plus ganirelix (0.25 mg/d, starting when the leading follicle was ≥16 mm; n=48). A single insemination was performed 36 hours after hCG was given (10,000 IU, IM) in both groups. Both groups were allowed at least three cycles. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate, premature luteinization rate, and follicular development. RESULT(S): Clinical pregnancy rate (22% vs. 11%), cumulative pregnancy rate (52% vs. 31%), and number of mature follicles (2.1±1.08 vs. 1.4±0.95) were statistically significantly higher in the ganirelix group compared with the control group. The premature luteinization rate was significantly lower in the ganirelix group (1.7% vs. 17.5%). CONCLUSION(S): The use of a GnRH antagonist in conjunction with controlled ovarian stimulation and IUI significantly increases pregnancy rates and reduces the incidence of premature luteinization.

Matrix metalloproteinases 2 and 9 and their tissue inhibitors in the follicular fluid of patients with polycystic ovaries undergoing in vitro fertilisation.

The present study was undertaken to investigate the levels of matrix metalloproteinase (MMP)-2, MMP-9 and their tissue inhibitors (TIMP-2 and TIMP-1, respectively) in the follicular fluid of 39 patients with polycystic ovary syndrome (PCOS) and compare them with the levels found in 56 age- and weight-matched normally ovulating women, all undergoing in vitro fertilisation (IVF) treatment. Significantly higher levels of MMP-2 and MMP-9 (p=0.02 and p<0.001, respectively) as well as TIMP-2 and TIMP-1 (p=0.006 and p<0.001, respectively) were found in the PCOS group compared to controls. Women who achieved pregnancy had higher TIMP-1 levels compared to the non-pregnant ones in the control group (p=0.01). In conclusion, women with PCOS exhibited significantly increased gelatinolytic activity compared with controls of similar age and body mass index, thus indicating a more intense extracellular matrix remodelling in this group of patients during IVF treatment due to multiple follicular development and cyst formation.

Intrafollicular levels of matrix metalloproteinases-2 and -9 in patients with polycystic ovaries are not associated with pregnancy rate during IVF cycle.

This study aimed to detect the levels of matrix metalloproteinases (MMP)-2 and -9, using enzyme-linked immunosorbent assays, in the follicular fluid of 35 patients with polycystic ovaries, compare them with the levels found in 35 normally ovulating women enrolled in their first in vitro fertilization (IVF) cycle and then correlate them with pregnancy rates in these two groups. Levels of MMP-9 were found significantly increased in women with polycystic ovaries when compared with the controls, while MMP-2 levels were higher in women with polycystic ovaries without reaching statistical significance. The two groups did not differ in age, in the number of embryos transferred or in pregnancy rates. In conclusion, the results indicated an increased gelatinolytic activity in patients with polycystic ovaries after ovarian stimulation for IVF treatment without detecting any association between levels of MMP-2 and 9 and IVF pregnancy rates.

Poor responders in IVF: cancellation of a first cycle is not predictive of a subsequent failure.

Management of women with a poor response to controlled ovarian hyperstimulation during IVF remains a frustrating challenge. The present study included 96 cycles from an equal number of women with a poor ovarian response and successful oocyte retrieval. Poor response was defined by the presence of at least one of the following characteristics: three or fewer oocytes on retrieval, serum estradiol level less than 500 pg/mL on the day of hCG administration, and serum FSH levels less than 20 IU/L. The same patients had a previous cycle cancelled because of a poor ovarian response whereas in the second cycle they preferred to continue the treatment despite the poor prognosis. We obtained 241 oocytes in the 96 IVF cycles. The fertilization rate was 60.2%. Three oocytes per cycle were retrieved in 56 cycles (58.3%), two oocytes per cycle in 33 cycles (34.4%), and one oocyte per cycle in 7 cycles (7.3%). In 19 cycles (19.8%) no fertilization was achieved. An embryo transfer was finally performed in 74 out of 96 cycles. Pregnancy rate was 12.5% per cycle and 16.2% per transfer. Among the 12 pregnancies achieved, 7 were in the 3-oocyte cycles and 5 in the 2-oocyte cycles. No pregnancies were achieved in the 1-oocyte cycles. Our data demonstrate that continuation of therapy in poor responders undergoing IVF can be an option despite the low pregnancy rates. The prognosis of these patients is not affected by a poor response in the first cycle and for some of them the outcome can be favorable.