Recurrent pregnancy loss is a complex health challenge with no universally accepted definition. Inconsistency in definitions involves not only the number of spontaneous abortions (two or three) that are accepted for recurrent pregnancy loss but the types of pregnancy and gestational age at miscarriage. Due to the heterogeneity of definitions and criteria applied by international guidelines for recurrent pregnancy loss, the true incidence of recurrent miscarriage, which is reported to range from 1% to 5%, is difficult to estimate. Moreover, the exact etiology of recurrent pregnancy loss remains questionable; thus, it is considered a polyetiological and multifactorial condition with many modifiable and non-modifiable factors involved. Even after thoroughly evaluating recurrent pregnancy loss etiology and risk factors, up to 75% of cases remain unexplained. This review aimed to summarize and critically analyze accumulated knowledge on the etiology, risk factors, relevant diagnostic options, and management approach to recurrent pregnancy loss. The relevance of various factors and their proposed roles in recurrent pregnancy loss pathogenesis remains a matter of discussion. The diagnostic approach and the management largely depend on the etiology and risk factors taken into consideration by a healthcare professional as a cause of recurrent miscarriage for a particular woman or couple. Underestimation of social and health consequences of recurrent pregnancy loss leads to compromised reproductive health and psychological well-being of women after miscarriage. Studies on etiology and risk factors for recurrent pregnancy loss, especially idiopathic, should be continued. The existing international guidelines require updates to assist clinical practice.

反复妊娠丢失（RPL）是困扰育龄期女性的常见疾病，胚胎染色体异常是导致RPL的最常见因素。近年来，随着植入前遗传学检测（PGT）技术的发展，可以更有效地避免因胚胎非整倍体导致的流产，PGT 在RPL患者中的临床应用日益广泛。文章回顾PGT技术自问世以来30年间的发展过程，从检测技术、活检技术、临床应用等方面，包括其在RPL中的应用进展做一阐述。

Preimplantation genetic screening (PGS) has increasingly been used in the past decade. Here we present a systematic review and meta-analysis of RCTs on the effect of PGS on the probability of live birth after IVF.PubMed and trial registers were searched for RCTs on PGS. Trials were assessed following predetermined quality criteria. The primary outcome was live birth rate per woman, secondary outcomes were ongoing pregnancy rate, miscarriage rate, multiple pregnancy rate and pregnancy outcome.Nine RCTs comparing IVF with and without PGS were included in our meta-analysis. Fluorescence in situ hybridization was used in all trials and cleavage stage biopsy was used in all but one trial. PGS significantly lowered live birth rate after IVF for women of advanced maternal age (risk difference: -0.08; 95% confidence interval: -0. 13 to -0.03). For a live birth rate of 26% after IVF without PGS, the rate would be between 13 and 23% using PGS. Trials where PGS was offered to women with a good prognosis and to women with repeated implantation failure suggested similar outcomes.There is no evidence of a beneficial effect of PGS as currently applied on the live birth rate after IVF. On the contrary, for women of advanced maternal age PGS significantly lowers the live birth rate. Technical drawbacks and chromosomal mosaicism underlie this inefficacy of PGS. New approaches in the application of PGS should be evaluated carefully before their introduction into clinical practice.

Can preimplantation genetic testing for aneuploidy (PGT-A) improve the live birth rate in patients with recurrent pregnancy loss (RPL)?

Can preimplantation genetic testing for aneuploidy (PGT-A) improve the live birth rate and reduce the miscarriage rate in patients with recurrent pregnancy loss (RPL) caused by an abnormal embryonic karyotype and recurrent implantation failure (RIF)?

In this retrospective study, the effect of preimplantation genetic testing for aneuploidy (PGT-A) was evaluated in women younger than 38 years with a history of one prior miscarriage and embryonic chromosomal abnormalities were detected in previous products of conception (POCs). Abnormal karyotypes were detected in POCs at our center between January 2014 and December 2017. Of the women included in this analysis, 124 continued with conventional in vitro fertilization/intracytoplasmic sperm injection cycles (non-PGT-A group) and 93 chose PGT-A cycles (PGT-A group), and the pregnancy outcomes in both groups were compared. Although the clinical pregnancy rate per embryo transfer was significantly higher in the PGT-A group (67.23% vs. 51.85%, p-adj = 0.01), no between-group differences were found in the live birth rate or miscarriage rate (45.38% vs. 40.74%, p-adj = 0.59; 16.25% vs. 14.29%, p-adj = 0.15). Women in both groups had comparative cumulative live birth rates (PGT-A vs. non-PGT-A, 58.06% vs. 53.23%, p = 0.48). The main results of this study suggest that PGT-A is not associated with an increased likelihood of a live birth or a decreased rate of miscarriage among women younger than 38 years without recurrent pregnancy loss and with a history of POCs with embryonic chromosomal abnormalities.

Preimplantation genetic testing (PGT) of embryos developed in vitro requires a biopsy for obtaining cellular samples for the analysis. Signs of cell injury have been described in association with this procedure. Thus, the consequences of the biopsy on obstetric and neonatal outcomes have been the subject of some quantitative analyses, although the reliability of data pooling may be limited by important issues in the various reports.

Subtle abnormalities in children's intelligence, motor skills, and psychology from various assisted reproductive treatments (ARTs) might be underdiagnosed. Understanding the prognosis of intelligence, motor skills, and psychology in children from ART would provide parents with reasonable expectations and enable them to plan relevant support to achieve the optimum potential in ART children.We searched PubMed, EMBASE, Ovid, Google Scholar, and Scopus databases until April 13, 2021, to identify relevant studies. Thirty-four studies met the inclusion and exclusion criteria. The meta-analysis employed a standardized mean difference model. The outcome of this study is to compare intelligence quotient (IQ), motoric ability, and behavioral problems between all ARTs, in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) to naturally conceived (NC) children. Subdomains of intelligence based on the Cattell, Horn, and Carroll Model (CHC Model) of cognitive architecture, including fluid reasoning, short-term and working memory, processing speed, visual-spatial ability, long-term memory retrieval, and crystalized intelligence (knowledge), were evaluated and summarized in details. Motor skill was stratified into two domains: gross motoric and fine motoric. Behavioral problem was categorized as externalizing and internalizing behavior.Meta-analysis showed that verbal intelligence score in IVF toddlers is significantly lower than NC toddlers (p = 0.02); conversely, ICSI toddlers scored significantly higher verbal intelligence score compared to NC toddlers (p = 0.005). Toddlers born after ART had significantly lower non-verbal intelligence score (p = 0.047). IVF toddlers scored significantly lower fine motor score (p = 0.01) compared to naturally conceived toddlers. Based on parent's CBCL, NC toddlers had higher total (p = 0.01) and externalizing behavior (p = 0.001) scores  compared to ART toddlers. Evaluation of full scale IQ and all domains of intelligence in preschool and primary school children revealed that no significant differences exist between ART and NC children. Based on preschool and primary school parents' CBCL, IVF children had significantly lower externalizing behavior score compared to NC children (p = 0.04). Meta-analyses of studies on young adolescents revealed that ART young adolescents scored higher academically than their NC counterparts, including on mathematics (p < 0.00001) and reading or language (p < 0.00001).Despite differences in certain aspects, this finding suggests that ART is unlikely to cause negative impacts on children's neurodevelopment.© 2023. BioMed Central Ltd., part of Springer Nature.

STUDY QUESTION: How reliable are cleavage stage and trophectoderm (TE) biopsies compared to inner cell mass (ICM) biopsies? SUMMARY ANSWER: The reliability of TE biopsy compared to ICM biopsy is almost perfect, but only substantial between cleavage stage biopsy and ICM biopsy. WHAT IS KNOWN ALREADY: One of the prevailing reasons for implantation failure is presumed to be chromosomal aneuploidy in human preimplantation embryos. Preimplantation genetic testing for aneuploidies (PGT-A) has been introduced into assisted reproduction in an effort to increase pregnancy rates. Increasing evidence indicates that genetic results obtained following blastomere or TEbiopsy may not accurately reflect the true genetic status of the embryo due to the presence of embryonic mosaicism, and therefore the reliability of PGT is highly controversial. STUDY DESIGN, SIZE, DURATION: This was an observational descriptive study, performed in a private infertility centre from August 2016 to January 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: The mean female age was 33.9 years, ranging from 24 to 46 years, and the mean number of biopsied embryos per couple was 2.2 (range 1-7 embryos). Blastomere biopsies had been performed at cleavage stage on Day 3 (D3) due to the turnover time of genetic testing and the inability to cryopreserve embryos in accordance with the local law governing ART. To confirm the genetic results in embryos not chosen for transfer, additional biopsies of the TE at blastocyst stage (BLASTO-TE) as well as of the ICM (BLASTO-ICM) were performed on D5. Only surplus blastocysts, which had not been selected for transfer and were not cryopreserved in accordance with the law governing ART, had been included. MAIN RESULTS AND THE ROLE OF CHANCE: Comparison of all biopsies (D3/BLASTO-ICM/BLASTO-TE) per embryo demonstrated that 50 (59.5%) out of 84 embryos showed concordance in all three results (= full concordance). Thirty-four (40.4%) embryos had at least two discordant results between the three biopsies, regardless of whether the embryo diagnosis (aneuploid/euploid) was discordant or not, or in aneuploid embryos, whether the chromosomal patterns were inconsistent. Nine (= 10.7%) embryos had complete discordance between all three biopsies. False positive results between D3/BLASTO-TE, D3/BLASTO-ICM and BLASTO-TE/BLASTO-ICM were 26.4%/30.2% and 7.5%, respectively, while the Kappa agreement between the different approaches was 0.647, 0.553 and 0.857, respectively. Therefore the reliability of D3/BLASTO-TE, D3/BLASTO-ICM and BLASTO-TE/BLASTO-ICM can be interpreted as substantial, as moderate and as almost perfect. LIMITATIONS, REASONS FOR CAUTION: The limitation of this study is the possible bias in the concordance/discordance rate because embryos that had been selected for transfer did not undergo biopsy on D5. WIDER IMPLICATIONS OF THE FINDINGS: The obvious discordance between the three different approaches for PGT-A underlines the limitations of genetic testing and highlights the importance of ongoing research in order to improve the accuracy of PGT-A results. Until then reproductive specialists will continue to make challenging decisions on whether to transfer or discard an embryo in light of current evidence questioning the reliability of genetic results.

To test the hypothesis that a freeze-all strategy would increase the chance of live birth compared with fresh embryo transfer in women with low prognosis for in vitro fertilisation (IVF) treatment.

Objective: The purpose of this study was to evaluate the impact of preimplantation genetic testing for aneuploidy (PGT-A) on clinical outcomes among high-risk patients.Methods: This retrospective study involved 1,368 patients and the same number of cycles, including 520 cycles with PGT-A and 848 cycles without PGT-A. The study participants comprised women of advanced maternal age (AMA) and those affected by recurrent implantation failure (RIF), recurrent pregnancy loss (RPL), or severe male factor infertility (SMF).Results: PGT-A was associated with significant improvements in the implantation rate (IR) and the ongoing pregnancy rate/live birth rate (OPR/LBR) per embryo transfer cycle in the AMA (39.3% vs. 16.2% [<i>p</i><0.001] and 42.0% vs. 21.8% [<i>p</i><0.001], respectively), RIF (41.7% vs. 22.0% [<i>p</i><0.001] and 47.0% vs. 28.6% [<i>p</i><0.001], respectively), and RPL (45.6% vs. 19.5% [<i>p</i><0.001] and 49.1% vs. 24.2% [<i>p</i><0.001], respectively) groups, as well as the IR in the SMF group (43.3% vs. 26.5%, <i>p</i>=0.011). Additionally, PGT-A was associated with lower overall incidence rates of early pregnancy loss in the AMA (16.7% vs. 34.3%, <i>p</i>=0.001) and RPL (16.7% vs. 50.0%, <i>p</i><0.001) groups. However, the OPR/LBR per total cycle across all PGT-A groups did not significantly exceed that for the non-PGT-A groups.Conclusion: PGT-A demonstrated beneficial effects in high-risk patients. However, our findings indicate that these benefits are more pronounced in carefully selected candidates than in the entire high-risk patient population.

There are a large number of infertile couples in China, but its treatment is notoriously expensive and not currently covered by insurance. The utility of preimplantation genetic testing for aneuploidy as an adjunct to in vitro fertilization has been debated.