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The objective of this prospective cohort study was to investigate the relationship between chronic endometritis (CE) and its treatment on pregnancy outcomes in patients undergoing frozen embryo transfers (FETs) from in vitro fertilization (IVF) with preimplantation genetic testing (PGT) who had previously failed ≥ 1 euploid FET. The diagnosis of CE was made using CD138 as a marker. This study occurred at a single, high volume academic based fertility center. 305 patients were included with a history of ≥ 1 failed euploid transfers. 59 patients underwent endometrial biopsies (EMB) prior to subsequent FET (Tested), 246 patients did not undergo EMB prior to subsequent transfer (Untested). Patients in the Tested group had an EMB prior to subsequent FET, whereas the patients in the Untested group did not have an EMB prior to next FET. Patients tested and found positive for CE were treated with antibiotics and underwent test-of-cure (TOC) EMBs prior to next FET to assess for adequate treatment. Patients without CE on EMB proceeded to next FET without antibiotic treatment. Main outcome measures included positive Beta-hCG (βhCG) on cycle day 28, implantation rate (IR), and subsequent ongoing pregnancy/live birth rates (OPR/LBR). Our results showed that 51% of patients (30/59) were diagnosed with CE and treated with antibiotics (Tested, CE treated); negative TOC biopsies were obtained prior to next FET. 49% of patients (29/59) tested negative for CE (Tested, No CE) and were not treated prior to next FET. Tested patients without CE (CE treated and No CE) had significantly higher incidences of positive βhCG, IR and OPR/LBR than patients who were not tested. Those who were biopsied and treated for CE had significantly higher OPR/LBR compared to patients who were biopsied and negative for CE (80% vs. 55%). We conclude that CE is common, with a prevalence of 51% in patients who have failed euploid FETs. Testing for CE may provide a benefit to patients, assuring higher incidences for positive βhCG, implantation, and subsequent ongoing/live births. CE is a treatable condition warranting investigation in patients with poor pregnancy outcomes.

Objective To validate and apply a strategy permitting parallel preimplantation genetic testing (PGT) for mitochondrial DNA (mtDNA) disease and aneuploidy (PGT-A). Design Preclinical test validation and case reports. Setting Fertility centers. Diagnostics laboratory. Patients Four patients at risk of transmitting mtDNA disease caused by m.8993T>G (Patients A and B), m.10191T>G (Patient C), and m.3243A>G (Patient D). Patients A, B, and C had affected children. Patients A and D displayed somatic heteroplasmy for mtDNA mutations. Interventions Embryo biopsy, genetic testing, and uterine transfer of embryos predicted to be euploid and mutation-free. Main Outcome Measures Test accuracy, treatment outcomes, and mutation segregation. Results Accuracy of mtDNA mutation quantification was confirmed. The test was compatible with PGT-A, and half of the embryos tested were shown to be aneuploid (16/33). Mutations were detected in approximately 40% of embryo biopsies from Patients A and D (10/24) but in none from Patients B and C (n = 29). Patients B and C had healthy children following PGT and natural conception, respectively. The m.8993T>G mutation displayed skewed segregation, whereas m.3243A>G mutation levels were relatively low and potentially impacted embryo development. Conclusions Considering the high aneuploidy rate, strategies providing a combination of PGT for mtDNA disease and aneuploidy may be advantageous compared with approaches that consider only mtDNA. Heteroplasmic women had a higher incidence of affected embryos than those with undetectable somatic mutant mtDNA but were still able to produce mutation-free embryos. While not conclusive, the results are consistent with the existence of mutation-specific segregation mechanisms occurring during oogenesis and possibly embryogenesis.

Study question To explore the effect of chromosomal mosaicism detected in preimplantation genetic testing (PGT-A) on prenatal and postnatal outcome of mosaic embryo pregnancies Summary answer No significant difference between euploid and mosaic embryos was observed in terms of weeks of gestation, average weight, and developmental defect of the babies born What is known already Mosaic embryos have the potential to implant and develop into healthy babies. Transfer of these embryos is now offered as an option for women who undergo IVF resulting in no euploid embryos. While, prenatal diagnosis has shown the depletion of chromosomal mosaicism in mosaic embryos, several concerns remain. For instance, the direct effects of different kind of mosaicism on prenatal/postnatal outcome and the possibility that intra-biopsy mosaicism in the TE is a poor predictor of the ploidy status of the ICM. Thus, there is certainly a need for comprehensive analyses of obstetrical and neonatal outcome data of transferred mosaic embryos. Study design, size, duration Compiled analysis from multicenter data on transfers of mosaic embryos (n = 1,000) and their outcome, with comparison to a euploid control group (n = 5,561). To explore the effect of embryonic mosaicism on newborns, we matched mosaic embryos resulting in a birth with a euploid embryo by a series of parameters (maternal age, embryo morphology, and indication for PGT-A). Prenatal tests and birth characteristics of > 200 neonates from mosaic embryo transfers were compared to > 200 euploid embryos. Participants/materials, setting, methods PGT-A was performed on blastocyst-stage embryos with 24-Chromosome whole genome amplification (WGA)-based Next Generation Sequencing (NGS). In accordance with established guidelines, embryos were categorized as mosaic when PGT-A results indicated 20-80% aneuploid content. Prenatal testing where performed in 30% of pregnancies with amniocentesis, 4% did an extra analysis for potential UPD for the suspected mosaic chromosome, and an additional 16% performed chorionic villus sampling (CVS) and 9.5% performed noninvasive prenatal testing (NIPT). Main results and the role of chance Of the 465 mosaic embryos that implanted, about 20% miscarried, and out of those, 75% were early spontaneous abortions. Of the pregnancies, 3 out of 368 were stillborn (2 out of them were twins that were extremely premature at 23 weeks, and the other died during pregnancy from a heart defect). The remaining 99% of those have been born or are late ongoing pregnancies at the time of analysis. Prenatal tests were performed in > 200 pregnancies and the vast majority tested normal. All 5 abnormal cases were amniocentesis tests showing microdeletions or insertions of sizes smaller than the resolution used during PGT-A, so they were unrelated to the mosaicism detected with PGT-A. In fact, in none of the cases did the prenatal test reflect the mosaicism detected at the embryonic stage. Matching each of the 162 mosaic embryos resulting in a birth with a euploid embryo, we found that the length of gestation was similar on average, and so was the average weight of the babies at birth. We also gathered information on the routine physical examination performed on babies at birth, and of those 162 babies from mosaic embryo transfers, none had obvious developmental defects or gross abnormalities. Limitations, reasons for caution Even though newborns resulting from mosaic embryo transfers in this study invariably appeared healthy by routine examination, concerns for long-term health cannot yet be entirely dispelled. The question must therefore be carefully considered by each clinic and patient situation. Wider implications of the findings Prenatal testing of > 200 pregnancies from mosaic embryo transfers showed no incidence of mosaicism that matched the PGT-A findings, indicating the involvement of self-corrective mechanisms. Pregnancy and obstetric data indicates that mosaic embryos prevailing through gestation and birth have similar chromosomal and physiological health compared to euploid embryos. Trial registration number none

PURPOSE: To assess the accuracy and reliability of comprehensive chromosome screening by next-generation sequencing (NGS) of human trophectoderm (TE) biopsy specimens. METHODS: The reliability and accuracy of diagnoses made by preimplantation genetic testing for aneuploidy (PGT-A) from TE biopsy were tested. Repeat biopsies of TE and inner cell mass (ICM) samples were obtained from thawed blastocysts previously tested by NGS. To test for the reliability of the NGS assay, biopsy samples were compared with the original PGT-A results. Prior NGS testing classified the TE samples as euploid, aneuploid, or aneuploid-mosaic. The resulting re-biopsied samples underwent SurePlex whole genome amplification followed by NGS via the MiSeq platform, with copy number value (CNV) determined using BlueFuse Multi Software. The primary outcome measure was reliability, defined as concordance between initial TE result and the repeat biopsies. Accuracy was determined by concordance between the TE and ICM samples, and compared between three chromosome types (disomic, aneuploid, and mosaic). RESULTS: Re-biopsies were performed on 32 embryos with prior PGT-A showing euploidy (10 embryos), aneuploidy of one or two chromosomes (4 embryos), or aneuploid-mosaic with one aneuploid chromosome and one mosaic chromosome (18 embryos). One hundred twenty-nine biopsy samples completed NGS (90 TE and 39 ICM biopsies) and 105 biopsy results were included in the analysis. TE biopsies provide a highly accurate test of the future fetus, with the ICM disomic concordance rate of 97.6%. Clinical concordance rates indicate that TE biopsies provide a reliable test when the result is euploid (99.5%) or aneuploid (97.3%), but less reliable when the result is mosaic (35.2%). CONCLUSION: TE biopsies predict euploidy or aneuploidy in the ICM with a high degree of accuracy. PGT-A with NGS of TE biopsies is shown to be highly reliable, with clinically relevant concordance rates for aneuploidy and euploidy over 95%. TE biopsies indicating mosaicism were less reliable (35.2%), presumably because mitotic non-disjunction events are not uniformly distributed throughout the blastocyst. However, classification of TE biopsy of PGT-A with NGS results as either aneuploid or euploid provides a highly reliable test.

Aneuploid conceptions constitute the majority of pregnancy failures in women of advanced maternal age. The best way to combat age-related decline in fertility is through preimplantation genetic testing for aneuploidy (PGT-A). PGT-A allows for better embryo selection, which improves implantation rates with single embryo transfer and reduces miscarriage rates. Single embryo transfers decrease multiple gestations and adverse pregnancy outcomes such as preterm or low birth weight infants. Advancements in extended embryo culture, blastocyst biopsy techniques, and 24-chromosome aneuploidy screening platforms have made PGT-A safe and accessible for all patients who undergo in vitro fertilization. Improved genomic coverage of new sequencing platforms, such as next-generation sequencing, has increased the identification and diagnosis of mosaicism and partial aneuploidies in preimplantation embryos. Mosaic embryos have decreased viability compared to euploid embryos when transferred, but some mosaic embryos result in normal live births. Whole genome amplification artifacts may contribute to a misdiagnosis of mosaicism, or some mosaic embryos may self-correct to euploid after implantation. For this reason, patients without euploid embryos should be given the option of transferring mosaic embryos after genetic counseling. Further research is needed to characterize which mosaic embryos may be viable.

Embryonic mosaicism occurs when two or more cell populations with different genotypes are present within the same embryo. New diagnostic techniques for preimplantation genetic screening (PGS), such as next-generation sequencing, have led to increased reporting of mosaicism. The interpretation of mosaicism is complicated because the transfer of some mosaic embryos has resulted in live births. Mosaic embryos may represent a third category between normal (euploidy) and abnormal (aneuploidy). This category of mosaic embryos may be characterized by decreased implantation and pregnancy potential as well as increased risk of genetic abnormalities and adverse pregnancy outcomes. Euploid embryos should be preferentially transferred over mosaic embryos. Genetic counseling is necessary before the transfer of a mosaic embryo is considered. Certain types of mosaic embryos should be preferentially transferred over others. Transfer of embryos with mosaic trisomies 2, 7, 13, 14, 15, 16, 18, and 21 may pose the most risk of having a child affected with a trisomy syndrome; however, the transfer of embryos with mosaic monosomies or other mosaic trisomies are not devoid of risk. Patients must be counseled about the risk of undetected monosomies or trisomies within a biopsy specimen as well as the risk of intrauterine fetal demise or uniparental disomy with the transfer of mosaic embryos. Until more data are available, patients should be encouraged to undergo another cycle to obtain euploid embryos, when possible, rather than transferring a mosaic embryo.

Objective To determine the pregnancy outcome potential of mosaic embryos, detected by means of preimplantation genetic screening (PGS) with the use of next-generation sequencing (NGS). Design Retrospective study. Setting Genetics laboratories. Patient(s) PGS cycles during which either mosaic or euploid embryos were replaced. Intervention(s) Blastocysts were biopsied and processed with the use of NGS, followed by frozen embryo transfer. Trophectoderm (TE) biopsies were classified as mosaic if they had 20%–80% abnormal cells. Main Outcome Measure(s) Implantation, miscarriage rates, and ongoing implantation rates (OIRs) were compared between euploid and types of mosaic blastocysts. Result(s) Complex mosaic embryos had a significantly lower OIR (10%) than aneuploidy mosaic (50%), double aneuploidy mosaic (45%), and segmental mosaic (41%). There was a tendency for mosaics with 40%–80% abnormal cells to have a lower OIR than those with Conclusion(s) Forty-one percent of mosaic embryos produced an ongoing implantation. Complex mosaic blastocysts had a lower OIR than other mosaics. Mosaic monosomies performed as well as mosaic trisomies and mosaic segmental aneuploidies. The results suggest that embryos with >40% abnormal cells and those with multiple mosaic abnormalities (chaotic mosaics) are likely to have lower OIRs and should be given low transfer priority.

Objective To evaluate whether the use of next generation sequencing (NGS) for preimplantation genetic screening (PGS) in single thawed euploid embryo transfer (STEET) cycles improves pregnancy outcomes compared with array comparative genomic hybridization (aCGH). Design Retrospective cohort study. Setting Single university-based fertility center. Patient(s) A total of 916 STEET cycles from January 2014 to December 2016 were identified. Cases included 548 STEET cycles using NGS for PGS and controls included 368 STEET cycles using aCGH for PGS. Intervention(s) Patients having a STEET after undergoing IVF and PGS with either NGS or aCGH. Main Outcome Measure(s) Primary outcomes were implantation rate, ongoing pregnancy/live birth rate (OP/LBR), biochemical pregnancy rate (PR), and spontaneous abortion (SAB) rate. Result(s) The implantation rate was significantly higher in the NGS group compared with the aCGH group (71.6% vs. 64.6%). The OP/LBR was also significantly higher in the NGS group (62% vs. 54.4%), and there were significantly more biochemical pregnancies in the aCGH group compared with the NGS group (15.1% vs. 8.7%). After adjustment for confounding variables with a multiple logistic regression analysis, OP/LBR remained significantly higher in the NGS group. The SAB rate was not significantly different in the NGS group compared with the aCGH group (12.4% vs. 12.7%). Conclusion(s) Preimplantation genetic screening using NGS significantly improves pregnancy outcomes versus PGS using aCGH in STEET cycles. Next-generation sequencing has the ability to identify and screen for embryos with reduced viability such as mosaic embryos and those with partial aneuploidies or triploidy. Pregnancy outcomes with NGS may be improved due to the exclusion of these abnormal embryos.

Study question Can quantification of mitochondrial DNA (mtDNA) in trophectoderm (TE) biopsy samples provide information concerning the viability of a blastocyst, potentially enhancing embryo selection and improving IVF treatment outcomes? Summary answer This study demonstrated that euploid blastocysts of good morphology, but with high mtDNA levels had a greatly reduced implantation potential. What is known already Better methods of embryo selection leading to IVF outcome improvement are necessary, as the transfer of chromosomally normal embryos of high morphological grade cannot guarantee the establishment of an ongoing pregnancy. The quantity of mtDNA in embryonic cells has been proposed as a new biomarker of viability-higher levels of mtDNA associated with reduced implantation potential. Study design, size, duration mtDNA was quantified in 199 blastocysts, previously biopsied and shown to be chromosomally normal using preimplantation genetic testing for aneuploidy (PGT-A). These were generated by 174 couples (average female age 37.06 years). All patients underwent IVF in a single clinic. The study took place in a blinded, non-selection manner-i.e. mtDNA quantity was not known at the time of single embryo transfer. The fate of the embryos transferred was subsequently compared to the mtDNA levels measured. Participants/materials, setting, methods Embryos were biopsied at the blastocyst stage. The TE samples obtained were subjected to whole genome amplification followed by comprehensive chromosome analysis via next generation sequencing. The same biopsy specimens were also tested using quantitative PCR, allowing highly accurate mtDNA quantification. After blastocyst transfer, the code used for blinding was broken and analysis undertaken to reveal whether the amount of mtDNA had any association with embryo implantation. Main results and the role of chance mtDNA analysis of the 199 blastocysts revealed that 9 (5%) contained unusually high levels of mtDNA. All embryo transfers involved a single chromosomally normal blastocyst of good morphology. Of these, 121 (60%) led to ongoing pregnancies, 11(6%) led to biochemical pregnancies, and 10 (5%) spontaneously miscarried. All (100%) of these blastocysts had mtDNA levels considered to be normal/low. The remaining 57 (29%) blastocysts failed to implant. Among these non-viable embryos there were 9 (16%) with unusually high levels of mtDNA. This meant that the ongoing pregnancy rate for morphologically good, euploid blastocysts, with normal/low levels of mtDNA was 64% (121/190). In contrast, the ongoing pregnancy rate for the same type of embryos, but with elevated mtDNA levels, was 0/9 (0%). This difference was highly statistically significant (P Limitations reasons for caution To determine the true extent of any clinical benefits a randomized clinical trial will be necessary. Research is needed to improve understanding of the biology of mtDNA expansion. Wider implications of the findings This is the first investigation to evaluate the clinical impact of increased mtDNA in a prospective blinded manner. Results confirm that embryos with elevated mtDNA rarely implant, supporting its use as a viability biomarker. A total of 64% of euploid blastocysts with normal/low mtDNA implanted versus 60% for the cohort as a whole. Study funding/competing interest(s) This study was supported by institutional funding (Reprogenetics UK and Reprogenetics). DW is supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre Programme. None of the authors have any competing interests.

STUDY QUESTION Does the amount of mitochondrial DNA (mtDNA) in blastocyst biopsy specimens have the potential to serve as a biomarker of euploid embryo implantation ability, independent of morphology? SUMMARY ANSWER The results of this study strongly suggest that elevated mtDNA levels, above a previously defined threshold, are strongly associated with blastocyst implantation failure and represent an independent biomarker of embryo viability. WHAT IS KNOWN ALREADY Improved methods of embryo selection are highly desirable in order to increase the efficiency of IVF treatment. At present, even the transfer of chromosomally normal embryos of high morphological grade cannot guarantee that a pregnancy will follow. Recently, it has been proposed that the quantity of mtDNA in embryonic cells may be an indicator of developmental potential, with higher levels of mtDNA associated with reduced implantation. However, thus far reported data sets have been relatively small and in some cases have lacked appropriate validation. STUDY DESIGN, SIZE, DURATION This large, blinded, retrospective study involved the analysis of relative mtDNA levels in 1505 euploid blastocysts obtained from 490 couples undergoing preimplantation genetic testing for aneuploidy. Implantation outcomes were compared to mtDNA levels in order to determine the capacity of the method to predict viability and to assess the validity of previously established thresholds. PARTICIPANTS/MATERIALS, SETTING, METHODS DNA from blastocyst biopsy samples was amplified and then subjected to aneuploidy analysis using next generation sequencing or array comparative genomic hybridization. Only those embryos classified as chromosomally normal had their mtDNA levels assessed. This analysis was undertaken retrospectively using quantitative real-time PCR, without knowledge of the outcome of embryo transfer. Predictions of implantation failure, based upon mtDNA levels were subsequently compared to the observed clinical results. All cycles involved the transfer of a single embryo. MAIN RESULTS AND THE ROLE OF CHANCE Of all blastocysts analyzed, 9.2% (139/1505) contained mtDNA levels above a previously established viability threshold and were therefore predicted to have reduced chances of implantation. To the date of analysis, 282 euploid blastocysts had been transferred with an overall implantation rate of 65.6% (185/282). Of the transferred embryos, 249 contained levels of mtDNA in the normal range, 185 of which produced a pregnancy, giving an implantation rate of 74.3% for euploid embryos with 'normal' quantities of mtDNA. However, 33 of the transferred embryos were determined to have elevated mtDNA quantities. None of these led to a pregnancy. Therefore, the negative predictive value of mtDNA assessment in this cohort was 100% (33/33). The difference between the implantation rates for embryos with normal and elevated mtDNA levels was highly significant (P < 0.0001). The mtDNA thresholds, used for classification of embryos, were unaffected by female age or the clinic in which the IVF was undertaken. The probability of an embryo having elevated levels of mtDNA was not influenced by variation in embryo morphology. LIMITATIONS, REASONS FOR CAUTION This study provides strong evidence that mtDNA quantification can serve as a valuable tool to assist the evaluation of blastocyst viability. However, to determine the true extent of any clinical benefits, other types of investigations, such as non-selection studies and randomized controlled trials, will also be necessary. WIDER IMPLICATIONS OF THE FINDINGS The results of this study suggest that mtDNA quantity can serve as an independent biomarker for the prediction of euploid blastocyst implantation potential. Prospective studies should now be undertaken to confirm these results. Additionally, investigations into the underlying biological cause(s) of elevated mtDNA levels and an enhanced understanding of how they relate to diminished implantation potential would be invaluable. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by funding provided by Reprogenetics. None of the authors have any competing interests.

The aim of this study was to report the results of IVF with trophectoderm biopsy and preimplantation genetic screening (PGS) following delayed intracytoplasmic sperm injection (ICSI).Patients undergoing IVF with PGS and delayed ICSI were included in the study. Indications for delayed ICSI included absent or poor fertilization via standard insemination or more than 50 % immature oocytes, noted post-cumulus stripping for standard ICSI procedure. Delayed ICSI was performed the day after retrieval due to absent or poor fertilization. The immature oocytes were kept in extended culture, and if demonstrated maturity, ICSI was performed. Primary outcome included fertilization rate and blastocyst stage formation, defined by the number of blastocysts for biopsy. Secondary outcome included aneuploidy rate and pregnancy outcomes following single thawed euploid embryo transfers (STEET).Sixteen patients with delayed ICSI were included in the study. Twelve were due to poor fertilization and four secondary to immature oocytes. A total of 219 oocytes were retrieved; ten were frozen upon patient request, 168 had standard insemination, and 13 had routine ICSI on the day of retrieval. A total of 129 oocytes underwent delayed ICSI. Sixty-three (49 %) fertilized, 19 (14.7 %) reached blastocysts for biopsy; fivw of which were chromosomally normal (26.3 %). Three patients underwent STEET of a delayed ICSI embryo; all three resulted in live births, including one embryo biopsied on day 8 of development.Fertilization failure or an excessive proportion of immature oocytes in an IVF cycle, necessitating delayed ICSI, showed equivalent fertilization and blast formation rates. With the implementation of trophectoderm biopsy and PGS, these embryos can lead to healthy live born babies.

We determined whether the use of intracytoplasmic sperm injection in couples who previously underwent intracytoplasmic sperm injection cycles elsewhere could be decreased without compromising the pregnancy rate.At our university in vitro fertilization-embryo transfer center we retrospectively analyzed the records of 149 fresh, in vitro fertilization-embryo transfer cycles in patients who underwent intracytoplasmic sperm injection elsewhere and subsequent fertilization by insemination only (all insemination group) or half insemination and half intracytoplasmic sperm injection at our center. We compared fertilization, implantation, clinical pregnancy and live birth rates.The fertilization rate was 74% and 73% for the all insemination and the half intracytoplasmic sperm injection groups, respectively. In the latter group 69% of inseminated and 78% of intracytoplasmic sperm injected oocytes were fertilized. No cycle showed complete fertilization failure. No statistically significant difference in the live birth rate was found between the 2 groups.More stringent criteria for intracytoplasmic sperm injection do not compromise the clinical outcome and reasonable fertilization can be achieved whether or not intracytoplasmic sperm injection is performed. Thus, although intracytoplasmic sperm injection is one of the greatest advances in our field, it is overused and should only be done for clinically proven indications.

Purpose: To analyze the correlation between lead follicle size at hCG trigger and IVF outcome. Methods: A review of all patients undergoing their first IVF cycle between 1/2005-12/2009 was performed. Four groups were evaluated (

Background Low functional ovarian reserve (LFOR) has been associated with hypoandrogenemia and increased embryo aneuploidy, while androgen supplementation has been reported to improve aneuploidy rates. We, therefore, assessed whether in infertile women undergoing in vitro fertilization (IVF) androgen concentrations are associated with aneuploidy rates. Methods This study was performed in 2 academically affiliated fertility centers in New York City and an academically affiliated steroid chemistry laboratory in Utah. Androgen concentrations were measured in blinded fashion from 84 infertile women (age 40.3 +/− 2.4 years) at New York University (NYU), using a validated LC-MS/MS method, in cryopreserved serum samples of patients who had undergone IVF with concomitant preimplantation genetic screening (PGS), utilizing a 24-chromosome platform. The Center for Human Reproduction (CHR) provided plasma samples of 100 historical controls (ages 38.6+/−5.0 years) undergoing IVF without PGS. Statistical comparisons were made of androgen concentrations, and of associations between androgen concentrations and embryo aneuploidy. Results Women undergoing IVF + PGS at NYU revealed no association between embryo aneuploidy and androgen concentrations but demonstrated significantly lower androgen concentrations than the 100 control patients from CHR, Conclusions Though this study revealed no association between androgen levels and embryo ploidy, the extremely low androgen levels in the NYU study group raise the possibility of a threshold effect below which testosterone no longer affects aneuploidy. Before an androgen effect on embryo ploidy can be completely ruled out, a patient population with more normal androgen levels has to be investigated.

In Vitro Fertilization is an effective treatment for infertility; however, it has relatively low success in women of advanced maternal age (>37) who have a high risk of producing aneuploid embryos, resulting in implantation failure, a higher rate of miscarriage or birth of a child with chromosome abnormalities. The purpose of this study was to compare the implantation, miscarriage and live birth rates with and without preimplantation genetic screening (PGS) of embryos from patients aged 40 through 43 years. This is a retrospective cohort study, comparing embryos screened for ploidy using trophectoderm biopsy and array comparative genomic hybridization to embryos that were not screened. We compared pregnancy outcomes for traditional fresh IVF cycles with day 5 embryo transfers, Frozen Embryo Transfer (FET) cycles without PGS and PGS-FET (FET of only euploid embryos) cycles of patients with maternal ages ranging from 40 to 43 years, undergoing oocyte retrievals during the period between 1/1/2011 and 12/31/2012. The implantation rate of euploid embryos transferred in FET cycles (50.9 %) was significantly greater than for unscreened embryos transferred in either fresh (23.8 %) or FET (25.4 %) cycles. The incidence of live birth per transferred embryo for PGS-FET (45.5 %) was significantly greater than for No PGS fresh (15.8 %) or No PGS FET (19.0 %) cycles. The incidences of live birth per implanted sac for PGS FET cycles (89.3 %), No PGS fresh cycles (66.7 %) and No PGS FET cycles (75.0 %) were not significantly different. The present data provides evidence of the benefits of PGS with regard to improved implantation and live birth rate per embryo transferred.

In human embryos, blastomeres differentiate into trophectoderm (TE) cells and inner cell mass (ICM) cells of blastocysts. Although morphologically indistinguishable, blastomeres at early cleavage stages are likely to undergo changes on a molecular level that make them destined to become ICM or TE cells. While the transcription factor Oct-4 might serve as a marker for totipotent ICM cells, human chorionic gonadotrophin might be used as the equivalent for TE cells. This study reports a reverse transcription-polymerase chain reaction procedure to assess human beta-HCG mRNA concentrations as well as ploidy in individual blastomeres from normally and abnormally fertilized human embryos. beta-HCG mRNA was detected in both euploid and aneuploid cells and in oocytes. Surprisingly, beta-LH mRNA was also detected in some euploid blastomeres. In regard to preimplantation genetic diagnosis, assessment of expression levels of beta-HCG and Oct-4 mRNA in individual biopsied cells might serve as a tool to identify embryogenic blastomeres in combination with testing for chromosome and single gene abnormalities.