Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of childbearing age. The risk of pregnancy and neonatal complications in women with PCOS is debatable. In order to determine the risk of pregnancy and neonatal complications, evidence regarding these risks was examined. Literature searches were performed in the electronic databases MEDLINE, EMBASE, and CENTRAL based on the established strategy and eligible tries were included according to inclusion and exclusion criteria. A systematic literature review looking at rates of gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), preeclampsia, premature delivery, neonatal birth weight, caesarean section and admission to a neonatal intensive care unit (NICU) was conducted in women with PCOS. Pregnancy outcomes between women with PCOS versus controls were included. Sensitivity analyses were performed to determine the reliability of the available evidence and to validate the results. The study was performed with the approval of the ethics committee of the First Affiliated Hospital of Guangxi Medical University. A total of 27studies, involving 4982 women with PCOS and 119692 controls were eligible for the meta-analysis. Women with PCOS demonstrated a significantly higher risk of developing GDM (OR3.43; 95% CI: 2.49–4.74), PIH (OR3.43; 95% CI: 2.49–4.74), preeclampsia (OR2.17; 95% CI: 1.91–2.46), preterm birth (OR1.93; 95%CI: 1.45–2.57), caesarean section (OR 1.74; 95% CI: 1.38–2.11) compared to controls. Their babies had a marginally significant lower birth weight (WMD −0.11g; 95%CI: -0.19 – -0.03), and higher risk of admission to NICU (OR 2.32; 95% CI: 1.40–3.85) compared to controls. Women with PCOS have increased risk of adverse pregnancy and neonatal complications. It is necessary to establish guidelines for supervision during pregnancy and parturition to prevent these complications.

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Obstetric complications in women with polycystic ovary syndrome: a systematic review and meta-analysis

Genetic diagnostic technologies are rapidly changing the way medicine is practiced. Preimplantation genetic testing is a well established application of genetic testing within the context of in vitro fertilization cycles. It involves obtaining a cell(s) from a developing embryo in culture, which is then subjected to genetic diagnostic analysis; the resulting information is used to guide which embryos are transferred into the uterus. The potential applications and use of this technology have increased in recent years. Experts agree that preimplantation genetic diagnosis is clinically appropriate for many known genetic disorders. However, some applications of such testing, such as preimplantation genetic screening for aneuploidy, remain controversial. Clinical data suggest that preimplantation genetic screening may be useful, but further studies are needed to quantify the size of the effect and who would benefit most.

https://www.bmj.com/content/bmj/350/bmj.g7611.full.pdf

Clinical applications of preimplantation genetic testing

Assessing the true incidence of mosaicism in preimplantation embryos

#### Summary points

Preimplantation genetic (PG) testing is the practice of obtaining a cellular biopsy sample from a developing human oocyte or embryo, acquired via a cycle of in vitro fertilisation (IVF); evaluating the genetic composition of this sample; and using this information to determine which embryos will be optimal for subsequent uterine transfer. PG testing was first described in 1990 when the sex of cleavage stage embryos in two couples, both with X linked diseases, was determined.1 The applications and use of various types of PG testing have continued to increase. However, the benefits and limitations of PG testing, both in popular culture and the medical community, are often misunderstood. This article reviews the technologies available in PG testing, and discusses the risks, ethical considerations, appropriateness, and controversy surrounding its use in different clinical situations.

#### Sources and selection criteria

The information sources used to compile this …

/pdf/preimplantation-genetic-testing-3wtt64danr.pdf

Preimplantation genetic testing.

STUDY QUESTION The aim of this study was to evaluate the live birth rate (LBR) after frozen-thawed Day 5 (D5) and Day 6 (D6) blastocyst transfers. SUMMARY ANSWER LBR following frozen-thawed blastocyst transfer is significantly lower with D6 than with D5 blastocyst regardless of embryo quality. WHAT IS KNOWN ALREADY During fresh embryo transfer cycles, pregnancy rates (PR) are significantly higher when transferring blastocysts expanded on D5 compared with slow developing blastocysts (D6). In programmed thawed blastocyst transfer (TBT) cycles, the same clinical outcomes should be expected when transferring D5 or D6 blastocysts because of endometrial/embryonic synchronization due to hormonal priming of endometrial receptivity. However, the impact of delayed blastocyst expansion at D6 on clinical outcomes remains unclear. Some reports have shown higher PRs after D5 TBT compared with those of D6, while others have shown equivalent TBT outcomes after D5 and D6 cryopreserved blastocysts transfers. STUDY, DESIGN, SIZE, DURATION This retrospective cohort follow-up study included 1347 single autologous frozen-thawed blastocyst transfers performed between January 2012 and December 2015 at a tertiary care university hospital. PARTICIPANTS/MATERIALS, SETTING, METHODS All of the patients scheduled for TBT were allocated to two groups according to the day of blastocyst expansion: on D5 (n = 994) or on D6 (n = 353). The primary outcome was LBR per embryo transfer in the first blastocyst thawing cycle. Secondary outcomes were clinical pregnancy rate (cPR), early miscarriage rate and neonatal outcomes following TBT for the two groups. Statistical analyses were conducted using univariate and multivariate logistic regression model. MAIN RESULTS AND THE ROLE OF CHANCE The LBR was significantly increased in the D5 group compared to the D6 group [294/994 (29.6%) versus 60/353 (17.0%); P < 0.001]. The cPR was also higher when blastocysts were vitrified on D5 compared with those vitrified on D6 [429/994 (43.2%) versus 95/353 (26.9%); P < 0.001]. No significant differences were found between groups in terms of early miscarriage rate (P = 0.862). More good-quality embryos (defined as an B3-B4 or B5 embryo ≥BB according to the grading scale proposed by Gardner) were transferred in the D5 group than in the D6 group [807 (81.2%) versus 214 (60.6%); P < 0.001]. However, a comparison of TBT cycles with equal embryo quality (good versus low) also supported the superiority of D5 blastocysts. Concerning neonatal outcomes, the D5 group infants had a lower mean birth weight compared to those of the D6 group (P = 0.001). In addition, a significantly shorter gestational age at birth is reported in the D5 blastocyst group as compared to the D6 group (P = 0.004). After multivariate logistic regression taking into account potential confounders such as the women's age, number of previous IVF/ICSI procedures, the day of the blastocyst vitrification (D5 or D6) and embryo quality, blastocyst expansion at D6 was independently associated with a significant decrease in LBR compared to D5 expanded-blastocysts (OR 0.52; 95% CI 0.38-0.72; P < 0.001). LIMITATIONS, REASONS FOR CAUTION The poor predictive value of the morphological approach in embryo selection could constitute a limitation in this study. However, blastocyst quality was evaluated similarly in both groups. WIDER IMPLICATIONS OF THE FINDINGS The LBR following frozen-thawed blastocyst transfer was significantly lower with D6 than with D5 blastocysts, regardless of their quality. These results could affect cryopreservation procedures as they suggest that the use of D5-expanded blastocysts for TBT may be preferred in order to shorten the time of conceiving. STUDY FUNDING/COMPETING INTEREST(S) No specific funding was obtained for this study. None of the authors have any competing interests to declare. TRIAL REGISTRATION NUMBER Not applicable.

Live birth rate following frozen-thawed blastocyst transfer is higher with blastocysts expanded on Day 5 than on Day 6.

Background: The sperm DNA fragmentation index (DFI) is widely regarded as a key measure for assessing male fertility, but the predictive value of the DFI for outcomes of assisted reproductive technology (ART) remains under debate. In this study, we used a large sample to analyze the effect of sperm DFI on pregnancy outcomes following ART and its relationship with oocyte fertilization and embryo development in in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). We also explore the value of sperm DNA fragmentation (SDF) and its associated factors in assessing male fertility.
 Methods: The relationship between the DFI measured with the sperm chromatin structure assay (SCSA) and pregnancy outcomes following ART were retrospectively analyzed in 2,622 ART treatment cycles, of which 1,185 were intrauterine insemination (IUI) cycles, 1,221 were IVF cycles and 216 were ICSI cycles. Rates of pregnancy, early abortion, oocyte fertilization and good quality embryos from IVF and ICSI cycles were compared between the groups of low DFI (DFI ≤15%), medium DFI (15% Results: Clinical pregnancy rates following IUI among high, medium, and low sperm DFI groups were 12.5% (11/88), 14.3% (48/336), and 13.4% (102/761), respectively, with no statistical difference between the groups (P=0.88); however, early abortion rates among these groups were 27.3% (3/11), 14.6% (7/48), and 4.9% (5/102), respectively, and the difference was statistically significant (P=0.02). No significant differences in the rates of clinical pregnancy, early abortion, oocyte fertilization, or good quality embryos in IVF or ICSI cycles were detected among different DFI groups (P Conclusions: As an increasingly common technique for reproductive testing, sperm DFI has proven to be very valuable in male fertility evaluation, but its significance as a predictor of pregnancy outcomes following ART requires further investigation.

/pdf/the-effect-of-sperm-dna-fragmentation-index-on-assisted-4ri5wnan76.pdf

The effect of sperm DNA fragmentation index on assisted reproductive technology outcomes and its relationship with semen parameters and lifestyle.

Whether there are differences in the pregnancy outcomes of blastocysts cryopreserved during different developmental stages remains under debate because the results among studies are inconsistent. We analyzed blastocyst quality and pregnancy outcomes by considering blastocyst euploidy and investigated the differences in the development potential between blastocysts of different developmental stages (frozen-thawed day 5 [D5] and day 6 [D6] cycles) and their relationship with clinical pregnancy outcomes. In total, 1374 D5 and 255 D6 frozen-thawed blastocyst transfer cycles were retrospectively analyzed. Additionally, the chromosome euploidy and clinical pregnancy rates of 237 blastocysts from 50 pre-implantation genetic diagnosis (PGS) cycles were statistically analyzed. The corresponding euploidy rate and pregnancy outcomes of the D5 and D6 blastocyst transfers were also compared. The clinical pregnancy rate (47.2 vs 40.0 %; P = 0.04) and implantation rate (34.2 vs 28.8 %; P = 0.03) of the D5 blastocysts were higher than were those of the D6 blastocysts. However, the clinical pregnancy rate (52.4 vs 52.6 %; P = 0.97) and implantation rate (38.9 vs 35.6 %; P = 0.39) of the high-quality D5 blastocysts did not significantly differ from those of the high-quality D6 blastocysts. Analysis of blastocyst euploidy in 237 blastocysts examined in 50 PGS cycles showed that the euploidy rates of the D5 and D6 blastocysts were both 48.1 % (P = 0.99). The clinical pregnancy rate of the D5 blastocysts (48.5 vs 17.6 %; P = 0.03) was higher than that of the D6 blastocysts. The euploidy rates (55.2 vs 55.3 %; P = 0.99) and clinical pregnancy rates (60.0 vs 42.9 %; P = 0.77) of the high-quality D5 and D6 blastocysts did not differ. The euploidy rate (55.3 vs 41.5 %, P = 0.03) and clinical pregnancy rate (54.5 vs 25.0 %, P = 0.03) of the high-quality blastocysts were higher than were those of the poor-quality blastocysts. The euploidy rates between the D5 and D6 blastocysts did not differ. High-quality D6 blastocysts in frozen-thawed cycles had similar developmental potential and pregnancy outcomes compared to those of high-quality D5 blastocysts. The quality of the blastocysts was an important factor that affected the pregnancy outcomes of the frozen-thawed cycles.

Comparison of differences in development potentials between frozen-thawed D5 and D6 blastocysts and their relationship with pregnancy outcomes.

Background: Female overweight/obesity has been reported to be associated with compromised pregnancy outcomes in fresh embryo transfer cycles. It is unclear whether the cumulative live birth rate (CLBR) is adversely affected after all viable embryos are transferred from the first ovarian stimulation cycle. Objectives: To investigate whether the CLBR was compromised in obese women. Method: A total of 9,772 young women underwent their first IVF/ICSI cycles from January 2012 to October 2017. Pregnancy outcomes were compared according to female BMI. Results: Among 1,671 women with polycystic ovary syndrome (PCOS), those with a BMI ≥ 28 kg/m2 had a lower cumulative clinical pregnancy rate (CCPR) and CLBR during the first complete ovarian stimulation cycle. Additionally, the pregnancy loss rate was increased in this group, although the difference was not significant. Among the 8,101 women without PCOS, the CCPR and CLBR of obese patients was also significantly decreased, and this group also showed increased pregnancy loss rates. Moreover, overweight women also had a decreased CLBR. Conclusions: Female obesity adversely affected the CLBR after utilizing the viable embryos from first oocytes retrieval.

/pdf/impact-of-female-obesity-on-cumulative-live-birth-rates-in-bi2otinv7d.pdf

Impact of Female Obesity on Cumulative Live Birth Rates in the First Complete Ovarian Stimulation Cycle.

We successfully performed preimplantation genetic diagnosis (PGD) and simultaneous preimplantation genetic screening (PGS) using single nucleotide polymorphism (SNP) microarrays for couples with balanced chromosome rearrangements in China. A total of 428 molecular karyotypes were diagnosed from 62 couples undergoing 68 in vitro fertilization (IVF) cycles. Of these, 48.1% of the embryos were chromosomally normal without translocation errors or aneuploidy. Of the 428 total embryos, 18.0% embryos were euploid, but were imbalanced due to the transmission of single translocation chromosome derivatives. A total of 6.5% of the embryos had chromosome abnormalities involving the parental chromosome aberration and other chromosomes aneuploidies. Significantly, 27.4% of the embryos were normal/balanced for the rearranged chromosomes, but were abnormal due to aneuploidy affecting other chromosomes. When evaluated on a per IVF cycle basis, 84% of the cycles had at least one chromosomally normal embryo availabl...

https://www.tandfonline.com/doi/pdf/10.3109/19396368.2013.875241

Increased IVF pregnancy rates after microarray preimplantation genetic diagnosis due to parental translocations

We investigated the incidence of aneuploidy in embryos from couples carrying monogenic diseases and the effect of embryo aneuploidy screening on the monogenic disease preimplantation genetic diagnosis (PGD). From November 2014 to April 2017, 36 couples carrying monogenic diseases were enrolled. The karyomap gene chip technique was used to analyze the blastocysts from the subjects and select normal embryos for transfer. A total of 43 single-gene PGD cycles were performed. A total of 687 eggs were obtained and 186 blastocysts were biopsed. After analysis via karyomap chip, 175 blastocysts received diagnostic results. In our monogenic disease PGD, 66.8% (117/175) of the embryos were diagnosed as normal or non-pathogenic (silent carriers), and 33.2% (58/175) of the embryos were diagnosed as abnormal or pathogenic. For preimplantation genetic screening (PGS), the aneuploidy rate of embryos was 22.9% (40/175). Among embryos diagnosed as normal for monogenic diseases, 26.5% (31/117) of the embryos were aneuploid and could not be transferred. Thus, approximately 1/4 of normal or non-pathogenic blastocysts diagnosed based on monogenic disease PGD were aneuploid, indicating the necessity and importance of embryo aneuploidy screening during PGD for monogenic diseases.

/pdf/importance-of-embryo-aneuploidy-screening-in-preimplantation-2nkg9z19zw.pdf

Gang Li

Papers

The effect of sperm DNA fragmentation index on assisted reproductive technology outcomes and its relationship with semen parameters and lifestyle.

Comparison of differences in development potentials between frozen-thawed D5 and D6 blastocysts and their relationship with pregnancy outcomes.

Impact of Female Obesity on Cumulative Live Birth Rates in the First Complete Ovarian Stimulation Cycle.

Increased IVF pregnancy rates after microarray preimplantation genetic diagnosis due to parental translocations

Importance of embryo aneuploidy screening in preimplantation genetic diagnosis for monogenic diseases using the karyomap gene chip