Publications by authors named "Zev Rosenwaks"

284 Publications

Psychosocial response of infertile patients to COVID-19-related delays in care at the epicenter of the global pandemic.

Minerva Obstet Gynecol 2021 May 28. Epub 2021 May 28.

The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, New York, NY, USA.

Background: To describe the psychosocial response of the infertile population whose care was curtailed due to the COVID-19 pandemic.

Methods: A web-based cross-sectional survey was administered to 117 infertile patients at our center who had their infertility treatment delayed due to suspension of care at our hospital during the COVID-19 pandemic. The survey consisted of 52-question multiple-choice questions including the Life Orientation Test-Revised (LOT-R) and the Hospital Anxiety and Depression Scale (HADS) instruments. Characteristics of respondents who "agreed" (strongly agree and agree) that "delaying treatment has permanently impacted my chances at future conception" were compared with participants who "disagreed" (neutral, disagree, and strongly disagree) using Fischer's exact test.

Results: In total, 79.5% agreed that delaying treatment has permanently impacted their chances at future conception. There were no discernible demographic differences between patients who "agreed" versus "disagreed" with the above statement. The mean LOT-R score was 14.1 (5.1) with an optimism score of 6.8 (2.6) and a pessimism score of 7.3 (2.9). The mean HADS depression score was 5.4 (3.4) with 28.2% reporting scores in the borderline-abnormal to abnormal range. The mean HADS anxiety score was 9.0 (3.9) with 64.6% reporting scores in the borderline-abnormal to abnormal range. Nearly one third of respondents (36.8%) reported wanting to "expedite/be more aggressive with treatment," whereas only 5.1% wanted to postpone treatment.

Conclusions: Women undergoing ART during the COVID-19 pandemic express significant concern and signs of distress about how delays in care affect their future reproductive potential.
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http://dx.doi.org/10.23736/S2724-606X.21.04852-1DOI Listing
May 2021

Combined transvaginal and transabdominal oocyte retrieval in a patient with an ectopic ovary and unicornuate uterus.

Fertil Steril 2021 May;115(5):1347-1349

Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, New York, New York.

Objective: To report the utility of combined transvaginal and transabdominal oocyte retrieval in a patient with an ectopic ovary and unicornuate uterus.

Design: Video case report with demonstration of oocyte retrieval technique.

Setting(s): University-affiliated fertility center.

Patient(s): A 35-year-old woman, gravida 0, with a 6-month history of infertility who presented to our center for fertility evaluation. Hysterosalpingography revealed a left unicornuate uterus and patent left fallopian tube magnetic resonance imaging and laparoscopy showed a right ectopic ovary located in the upper abdomen. Her partner was a 36-year-old male with isolated teratozoospermia. The couple did not conceive with intrauterine insemination.

Intervention(s): Ovarian stimulation for in vitro fertilization (IVF). Transvaginal retrieval of oocytes from the right ovary was not deemed possible due the anatomic location of the ovary, intervening blood vessels, and limited mobility of the ovary. Institutional review board approval was not required for this case report as per our institution's policy; patient consent was obtained for publication of the case.

Main Outcome Measure(s): Transabdominal retrieval of oocytes from the right ovary and transvaginal retrieval of oocytes from the left ovary.

Result(s): The couple underwent two IVF cycles. Nine oocytes were retrieved during the first IVF cycle: seven transabdominal (right ovary) and two transvaginal (left ovary). All oocytes were mature, and five blastocysts were cryopreserved. Eight oocytes were retrieved during the second IVF cycle, of which five oocytes were retrieved transabdominally from the right ovary, and three oocytes were retrieved transvaginally from the left ovary. All oocytes were mature, and four blastocysts were cryopreserved. A single thawed embryo was transferred in the natural menstrual cycle, which resulted in the live birth of a full-term baby boy weighing 2,410 grams.

Conclusion(s): The current case highlights the safety and feasibility of combined transvaginal and transabdominal oocyte retrieval in patients with an ectopic ovary located in the upper abdomen.
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http://dx.doi.org/10.1016/j.fertnstert.2020.12.006DOI Listing
May 2021

Reproductive and obstetric outcomes in women of racial minorities aged 40 years and older undergoing IVF.

Reprod Biomed Online 2021 Jun 30;42(6):1181-1186. Epub 2021 Jan 30.

The Ronald O Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, 1305 York Avenue, 6th Floor New York, New York 10021, USA.

Research Question: Do women of racial minorities aged 40 years or older have similar reproductive and obstetric outcomes as white women undergoing IVF?

Design: A retrospective cohort study conducted at a single academic university-affiliated centre. The study population included women aged 40 years or older undergoing their first IVF cycle with fresh cleavage-stage embryo transfer stratified by racial minority status: minority (black or Asian) versus white. Clinical intrauterine pregnancy and live birth rate were the primary outcomes. Preterm delivery (<37 weeks) and small for gestational age were the secondary outcomes. Odds ratios with 95% confidence intervals were estimated. P < 0.05 was considered to be statistically significant.

Results: A total of 2050 cycles in women over the age of 40 years were analysed, 561 (27.4%) of which were undertaken by minority women and 1489 (72.6%) by white women. Minority women were 30% less likely to achieve a pregnancy compared with their white (non-Hispanic) counterparts (adjusted OR 0.68, CI 0.54 to 0.87). Once pregnant, however, the odds of live birth were similar (adjusted OR 1.23, CI 0.91 to 1.67). Minority women were significantly more likely to have lower gestational ages at time of delivery (38.5 versus 39.2 weeks, P = 0.009) and were more likely to have extreme preterm birth delivery 24-28 weeks (5.5 versus 1.0%, P = 0.021).

Conclusion: Minority women of advanced reproductive age are less likely to achieve a pregnancy compared with white (non-Hispanic) women. Once pregnancy is achieved, however, live birth rates are similar albeit with minority women experiencing higher rates of preterm delivery.
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http://dx.doi.org/10.1016/j.rbmo.2021.01.018DOI Listing
June 2021

Is increasing paternal age negatively associated with donor oocyte recipient success? A paired analysis using sibling oocytes.

Fertil Steril 2021 Apr 26. Epub 2021 Apr 26.

Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, New York.

Objective: To determine if increasing paternal age has an adverse effect on pregnancy outcomes in paired donor egg recipients who received oocytes from the same donor in the same stimulation cycle.

Design: Retrospective cohort study.

Setting: Reproductive Medicine Center.

Patient(s): The study included 154 recipients who received oocytes from a split donor oocyte cycle and received sperm from men in discrepant age groups (group A: <45 years old; group B: ≥45 years old).

Intervention(s): None.

Main Outcome Measure(s): Implantation rate, pregnancy loss rate, pregnancy rate, and live birth rate.

Result(s): The median paternal age was 41 years old for group A and 48 years old for group B. The pregnancy rate was 81% in group A compared with 69% in group B. The live birth rate was 65% in group A compared with 53% in group B. The rate of pregnancy loss was 19% in group A and 23% in group B. The implantation rate was 69% in group A compared with 66% in group B. The adjusted odds of pregnancy were found to be 65% lower for patients in the older partner age group (95% confidence interval [CI], 0.13, 0.95). The adjusted odds of live birth rate (odds ratio [OR], 0.45; 95% CI, 0.20, 1.00), implantation rate (OR, 0.91; 95% CI, 0.43, 1.92), and rate of pregnancy loss (OR, 1.5; 95% CI, 0.5, 4.5) favored the younger partner age group; however, these results were not statistically significant.

Conclusion(s): In this model that controlled for oocyte quality to the greatest degree possible by using paired recipients from the same donor from the same stimulation cycle, we found that increased paternal age had a negative effect on pregnancy rates.
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http://dx.doi.org/10.1016/j.fertnstert.2021.03.037DOI Listing
April 2021

Single-center thorough evaluation and targeted treatment of globozoospermic men.

J Assist Reprod Genet 2021 Apr 20. Epub 2021 Apr 20.

The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, 1305 York Avenue, Y720, New York, NY, 10021, USA.

Purpose: To characterize, by specific biomarkers and nucleic acid sequencing, the structural and genomic sperm characteristics of partial (PG) and complete globozoospermic (CG) men in order to identify the best reproductive treatment.

Methods: We assessed spermatozoa from 14 consenting men ultrastructurally, as well as for histone content, sperm chromatin integrity, and sperm aneuploidy. Additional genomic, transcriptomic, and proteomic evaluations were carried out to further characterize the CG cohort. The presence of oocyte-activating sperm cytosolic factor (OASCF) was measured by a phospholipase C zeta (PLCζ) immunofluorescence assay. Couples were treated in subsequent cycles either by conventional ICSI or by ICSI with assisted gamete treatment (AGT) using calcium ionophore (Ionomycin, 19657, Sigma-Aldrich, Saint Louis, MO, USA).

Results: Ultrastructural assessment confirmed complete acrosome deficiency in all spermatozoa from CG men. Histone content, sperm chromatin integrity, and sperm aneuploidy did not differ significantly between the PG (n = 4) and CG (n = 10) cohorts. PLCζ assessment indicated a positive presence of OASCF in 4 PG couples, who underwent subsequent ICSI cycles that yielded a 36.1% (43/119) fertilization with a 50% (2/4) clinical pregnancy and delivery rate. PLCζ assessment failed to detect OASCF for 8 CG patients who underwent 9 subsequent ICSI cycles with AGT, yielding a remarkable improvement of fertilization (39/97; 40.2%) (P = 0.00001). Embryo implantation (6/21; 28.6%) and clinical pregnancies (5/7; 71.4%) were also enhanced, resulting in 4 deliveries. Gene mutations (DPY19L2, SPATA16, PICK1) were identified in spermatozoa from CG patients. Additionally, CG patients unable to sustain a term pregnancy had gene mutations involved in zygote development (NLRP5) and postnatal development (BSX). CG patients who successfully sustained a pregnancy had a mutation (PIWIL1) related to sperm phenotype. PLCZ1 was both mutated and underexpressed in these CG patients, regardless of reproductive outcome.

Conclusions: Sperm bioassays and genomic studies can be used to characterize this gamete's capacity to support embryonic development and to tailor treatments maximizing reproductive outcome.
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http://dx.doi.org/10.1007/s10815-021-02191-4DOI Listing
April 2021

Reproductive Endocrinology and Infertility fellowship programs: Does one size fit all?

Fertil Steril 2021 Mar;115(3):569-575

Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, New York, New York. Electronic address:

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http://dx.doi.org/10.1016/j.fertnstert.2021.01.036DOI Listing
March 2021

Training the next generation of reproductive endocrinology and infertility subspecialists.

Fertil Steril 2021 Mar;115(3):567-568

Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, New York, New York.

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http://dx.doi.org/10.1016/j.fertnstert.2021.01.035DOI Listing
March 2021

Time from oocyte retrieval to frozen embryo transfer in the natural cycle does not impact reproductive or neonatal outcomes.

Fertil Steril 2021 May 12;115(5):1232-1238. Epub 2021 Feb 12.

The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, New York, New York. Electronic address:

Objective: To determine if the time from oocyte retrieval to frozen embryo transfer (FET) in the natural cycle affects reproductive or neonatal outcomes.

Design: Retrospective cohort.

Setting: Not applicable.

Patient(s): Five hundred and seventy-six consecutive freeze-all cycles from January 2011 to December 2018 followed by natural cycle FET of a single blastocyst.

Intervention(s): None.

Main Outcome Measure(s): Primary outcome of live birth; secondary outcomes of preterm delivery (24-37 weeks) and small for gestational age (SGA) with a multivariable logistic regression performed with adjustment for age, infertility diagnosis, ovulatory trigger type, and preimplantation genetic testing (PGT).

Result(s): Before adjustment for confounding, we found a statistically significantly different live-birth rate (57.7% vs. 48.6%) for natural cycle FET occurring in the first versus second menstrual cycle, respectively. In a multivariate analysis, performing a natural cycle FET of a single blastocyst in the second compared with the first menstrual cycle did not statistically significantly impact the odds of live-birth rate. After adjustment for age, diagnosis, and ovulatory trigger type, only PGT was associated with statistically significantly increased odds of live birth compared with no PGT. There were no differences in the incidence of SGA (male, 6.6% vs. 2.3%; female, 9.8% vs. 11.1%) or preterm delivery (1.6% vs. 5.6%) between both groups.

Conclusion(s): Performing a natural cycle FET of a single blastocyst in the second compared with the first menstrual cycle after ovarian stimulation did not statistically significantly impact the odds of live birth or neonatal outcomes.
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http://dx.doi.org/10.1016/j.fertnstert.2020.11.011DOI Listing
May 2021

Pluripotent stem cell-derived epithelium misidentified as brain microvascular endothelium requires ETS factors to acquire vascular fate.

Proc Natl Acad Sci U S A 2021 Feb;118(8)

Ansary Stem Cell Institute, Division of Regenerative Medicine, Department of Medicine, Weill Cornell Medicine, New York, NY 10065;

Cells derived from pluripotent sources in vitro must resemble those found in vivo as closely as possible at both transcriptional and functional levels in order to be a useful tool for studying diseases and developing therapeutics. Recently, differentiation of human pluripotent stem cells (hPSCs) into brain microvascular endothelial cells (ECs) with blood-brain barrier (BBB)-like properties has been reported. These cells have since been used as a robust in vitro BBB model for drug delivery and mechanistic understanding of neurological diseases. However, the precise cellular identity of these induced brain microvascular endothelial cells (iBMECs) has not been well described. Employing a comprehensive transcriptomic metaanalysis of previously published hPSC-derived cells validated by physiological assays, we demonstrate that iBMECs lack functional attributes of ECs since they are deficient in vascular lineage genes while expressing clusters of genes related to the neuroectodermal epithelial lineage (Epi-iBMEC). Overexpression of key endothelial ETS transcription factors (, , and ) reprograms Epi-iBMECs into authentic endothelial cells that are congruent with bona fide endothelium at both transcriptomic as well as some functional levels. This approach could eventually be used to develop a robust human BBB model in vitro that resembles the human brain EC in vivo for functional studies and drug discovery.
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http://dx.doi.org/10.1073/pnas.2016950118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923590PMC
February 2021

Detection of early placental hormone production in embryo transfer cycles lacking a corpus luteum.

J Assist Reprod Genet 2021 Feb 4;38(2):413-419. Epub 2021 Jan 4.

The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, 1305 York Avenue 6th Floor, New York, NY, 10021, USA.

Purpose: This study sought to identify the initiation of placental hormonal production as defined by the production of endogenous estradiol (E2) and progesterone (P4) in a cohort of patients undergoing programmed endometrial preparation cycles with single embryo transfers resulting in live-born singletons.

Methods: In this retrospective cohort study, patients undergoing either programmed frozen-thawed embryo transfer (FET) with autologous oocytes or donor egg recipient (DER) cycles with fresh embryos were screened for inclusion. Only patients who underwent a single embryo transfer, had a single gestational sac, and a resultant live-born singleton were included. All patients were treated with E2 patches and intramuscular progesterone injections. Main outcome measures were serial E2 and P4, with median values calculated for cycle days 28 (baseline), or 4w0d gestational age (GA), through 60, or 8w4d GA. The baseline cycle day (CD) 28 median value was compared to each daily median cycle day value using the Wilcoxon signed rank test.

Results: A total of 696 patients, 569 using autologous oocytes in programmed FET cycles and 127 using fresh donor oocytes, from 4/2013 to 4/2019 met inclusion criteria. Serum E2 and P4 levels stayed consistent initially and then began to increase daily. Compared to baseline CD 28 E2 (415 pg/mL), the serum E2 was significantly elevated at 542 pg/mL (P < 0.001) beginning on CD 36 (5w1d GA). With respect to baseline CD 28 P4 (28.1 ng/mL), beginning on CD 48 (6w6d GA), the serum P4 was significantly elevated at 31.6 ng/mL (P < 0.001).

Conclusion: These results demonstrate that endogenous placental estradiol and progesterone production may occur by CD 36 and CD 48, respectively, earlier than traditionally thought.
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http://dx.doi.org/10.1007/s10815-020-02049-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884517PMC
February 2021

Clinical implications of telemedicine for providers and patients.

Fertil Steril 2020 12;114(6):1129-1134

Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, New York.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in paradigm shifts in the delivery of health care. Lockdowns, quarantines, and local mandates forced many physician practices around the United States to move to remote patient visits and adoption of telemedicine. This has several long-term implications in the future practice of medicine. In this review we outline different models of integrating telemedicine into both male and female fertility practices and recommendations on performing video physical examinations. Moving forward we foresee two general models of integration: one conservative, where initial intake and follow-up is performed remotely, and a second model where most visits are performed via video and patients are only seen preoperatively if necessary. We also discuss the impact THAT telemedicine has on coding and billing and our experience with patient satisfaction.
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http://dx.doi.org/10.1016/j.fertnstert.2020.10.048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024108PMC
December 2020

Optimal lead follicle size for human chorionic gonadotropin trigger in clomiphene citrate and intrauterine insemination cycles: an analysis of 1,676 treatment cycles.

Fertil Steril 2021 Apr 4;115(4):984-990. Epub 2020 Dec 4.

Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, New York, New York.

Objective: To identify the optimal lead follicle size for hCG trigger in clomiphene citrate (CC)-intrauterine insemination (IUI) cycles.

Design: Retrospective cohort study.

Setting: University-affiliated center.

Patient(s): Patients <40 years of age with ovulatory dysfunction or unexplained infertility undergoing their first CC-IUI cycle.

Intervention(s): Ovulation induction, hCG trigger, and IUI.

Main Outcome Measure(s): Clinical pregnancy rate (CPR) was the primary outcome and was plotted against lead follicle size in increments of 1 mm. Odds ratios with 95% confidence intervals for associations between lead follicle size and CPR were calculated from a multivariable logistic regression model. A receiver operating characteristic (ROC) curve was generated for CPR as a function of lead follicle size.

Result(s): 1,676 cycles were included. The overall CPR was 13.8% (232/1,676). There was no difference in baseline demographics or ovulation induction parameters of patients who did or did not conceive. The odds of clinical pregnancy were 2.3 and 2.2 times higher with lead follicle sizes of 21.1-22.0 mm and >22.0 mm, respectively, compared with the referent category of 19.1-20.0 mm. Lead follicle size was an independent predictor of CPR, even after accounting for confounders. A lead follicle size of 22.1 mm corresponded to a sensitivity and specificity of 80.1% and 90.4% for clinical pregnancy, respectively, with an area under the ROC curve of 0.89.

Conclusion(s): hCG administration at a lead follicle size of 21.1-22.0 mm is associated with higher odds of clinical pregnancy in patients undergoing their first CC-IUI cycles for ovulatory dysfunction or unexplained infertility.
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http://dx.doi.org/10.1016/j.fertnstert.2020.10.026DOI Listing
April 2021

Assessing the cognitive and behavioral development of 3-year-old children born from fathers with severe male infertility.

Am J Obstet Gynecol 2021 05 26;224(5):508.e1-508.e11. Epub 2020 Nov 26.

Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, NY. Electronic address:

Background: Despite the large number of babies born worldwide following intracytoplasmic sperm injection, concerns about the procedure's safety still exist owing to the use of suboptimal spermatozoa. Thus, follow-up of children conceived via intracytoplasmic sperm injection is highly recommended. We propose the use of parent-administered questionnaires to monitor the development of offspring conceived via intracytoplasmic sperm injection.

Objective: This study aimed to determine whether male infertility treatment affects offspring development.

Study Design: We compared obstetrical and neonatal outcomes and physical and psychological development of toddlers conceived via in vitro fertilization and intracytoplasmic sperm injection. Once newborns reached 3 years of age, participating patients were sent a set of parent-administered questionnaires, including the Ages and Stages Questionnaires; Prescreening Developmental Questionnaire 2; Peabody Developmental Motor Scales, Second Edition; Social Skills Rating System; Parenting Stress Index, Third Edition; and Child Behavior Checklist for Ages 2-3. Child development was measured by the Ages and Stages Questionnaires; Prescreening Developmental Questionnaire 2; and Peabody Developmental Motor Scales, Second Edition, questionnaires, whereas Social Skills Rating System; Parenting Stress Index, Third Edition; and Child Behavior Checklist for Ages 2-3 questionnaires were used to measure child behavior. The child's developmental or behavioral outcome was considered "abnormal" when he or she scored below average in ≥2 questionnaires from the respective category. We also conducted subanalyses to assess the effects of male genomic integrity, DNA fragmentation, chemical exposure, utilization of surgically retrieved spermatozoa, and extended embryo culture to determine the development of a child conceived via intracytoplasmic sperm injection.

Results: A total of 12,306 couples met the inclusion criteria for this study; 1914 of 7433 patients (25.8%) who underwent intracytoplasmic sperm injection and 451 of 4873 patients (9.3%) who underwent in vitro fertilization returned the questionnaires. Our comparison of obstetrical outcomes between the 2 groups did not reveal any significant differences in the mode of delivery distribution, with most mothers having uncomplicated vaginal deliveries. Furthermore, gender distribution, gestational ages, and birthweights were also comparable between children conceived via intracytoplasmic sperm injection and in vitro fertilization. However, children conceived via in vitro fertilization displayed impaired developmental characteristics compared with the intracytoplasmic sperm injection-conceived cohort (adjusted odds ratio, 0.72; 95% confidence interval, 0.5-0.9; P=.0004). There was no difference in child behavior. Furthermore, 3 cases of autism were reported, 1 case from the in vitro fertilization group and 2 from the intracytoplasmic sperm injection group, all conceived from couples with an older male partner. Ages and Stages Questionnaires outcomes were also compared for the offspring conceived via in vitro fertilization and intracytoplasmic sperm injection by gender; however, no significant differences were observed. In addition, 5 separate subanalyses were then conducted exclusively for the intracytoplasmic sperm injection-conceived group. Levels of spermatogenic failure, DNA fragmentation, and chemical exposure did not significantly affect offspring development. Interestingly, although the length of embryo culture did not seem to influence child development, the abnormal behavior rate was significantly higher in children from the day 3 embryo transfer cohort (adjusted odds ratio, 0.4; 95% confidence interval, 0.05-0.34; P=.04). Children conceived via intracytoplasmic sperm injection from ejaculated spermatozoa displayed impaired developmental and behavioral characteristics compared with toddlers conceived from surgically retrieved specimens (adjusted odds ratio, 4.9; 95% confidence interval, 1.2-20.7; P=.05).

Conclusion: Most children conceived via intracytoplasmic sperm injection and in vitro fertilization are developing well without significant delays. Although the development of a child conceived via intracytoplasmic sperm injection was not affected by most of the variables assessed, those conceived from surgically retrieved spermatozoa were at a considerably lower risk of abnormal developmental and abnormal behavioral characteristics than offspring conceived from ejaculated specimens. However, given the small numbers of respondents available for many subgroups of interest, further studies of outcomes of children born from fathers with severe male factor infertility are warranted.
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http://dx.doi.org/10.1016/j.ajog.2020.11.030DOI Listing
May 2021

Reproductive and obstetric outcomes in mildly and significantly underweight women undergoing IVF.

Reprod Biomed Online 2021 Feb 24;42(2):366-374. Epub 2020 Oct 24.

The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical Center, New York NY, USA. Electronic address:

Research Question: What is the impact of low body mass index (BMI) on live birth rates and obstetric outcomes in infertile women treated with IVF and fresh embryo transfer?

Design: This was a retrospective cohort study of infertile patients in an academic hospital setting who underwent their first oocyte retrieval with planned autologous fresh embryo transfer between 1 January 2012 and 31 December 2018. The primary study outcome was live birth rate. Secondary outcomes were IVF treatment and delivery outcomes. Underweight patients were stratified into a significantly underweight group (body mass index [BMI] <17.5 kg/m) and a mildly underweight group (BMI 17.5-18.49 kg/m), and were compared with a normal-weight group (BMI 18.5-24.9 kg/m).

Results: A total of 5229 patients were included (significantly underweight, 76; mildly underweight, 231; normal weight, 4922), resulting in 4798 embryo transfers. After oocyte retrieval, there were no significant differences between groups for total oocytes, mature oocyte yield and number of supernumerary blastocysts cryopreserved. Among women who had an embryo transfer, there were no significant differences in the live birth rates in significantly (31.0%, odds ratio [OR] 0.67, confidence interval [0.95, CI] 0.40-1.13) and mildly (37.7%, OR 0.95, CI 0.73-1.33) underweight patients compared with normal-weight patients (35.9%). Additionally, there were no statistically significant increased risks of preterm delivery, Caesarean delivery or a low birthweight (<2500 g) neonate.

Conclusions: Mildly and significantly underweight infertile women have similar pregnancy and live birth rates to normal-weight patients after IVF treatment. In addition, underweight patients do not have an increased risk of preterm delivery (<37 weeks), Caesarean delivery or a low birthweight neonate.
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http://dx.doi.org/10.1016/j.rbmo.2020.10.011DOI Listing
February 2021

Live birth outcomes in infertile patients with class III and class IV obesity following fresh embryo transfer.

J Assist Reprod Genet 2021 Feb 16;38(2):347-355. Epub 2020 Nov 16.

The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical Center, 1305 York Avenue, New York, NY, 10021, USA.

Objective: Assess the effect of class III (body mass index [BMI, kg/m] 40-49.9) and class IV obesity (≥ 50) on clinical pregnancy and live birth outcomes after first oocyte retrieval and fresh embryo transfer cycle.

Design: Cohort study SETTING: Academic center PATIENTS: Patients undergoing their first oocyte retrieval with planned fresh embryo transfer in our clinic between 01/01/2012 and 12/31/2018. Patients were stratified by BMI: 18.5-24.9 (n = 4913), 25-29.9 (n = 1566) 30-34.9 (n = 559), 35-39.9 (n = 218), and ≥ 40 (n = 114).

Intervention: None MAIN OUTCOME MEASURE: Live birth rate RESULTS: Following embryo transfer, there were no differences in pregnancy rates across all BMI groups (p value, linear trend = 0.86). However among pregnant patients, as BMI increased, a significant trend of a decreased live birth rate was observed (p value, test for linear trend = 0.004). Additionally, as BMI increased, a significant trend of an increased miscarriage rate was observed (p value, linear trend = < 0.001). Compared to the normal-weight cohort, women with a BMI ≥ 40 had a significantly higher rate of cancelled fresh transfers after retrieval (18.4% vs. 8.2%, OR 2.51; 95%CI 1.55-4.08). Among singleton deliveries, a significant trend of an increased c-section rate was identified as the BMI increased (p value, linear trend = <0.001).

Conclusion: Overall, patients with a BMI > 40 have worse IVF treatment outcomes compared to normal-weight patients. After embryo transfer, their pregnancy rate is comparable to normal-weight women; however, their miscarriage rate is higher, leading to a lower live birth rate for pregnant women in this population. Patients with a BMI > 40 have a c-section rate that is 50% higher than normal-weight patients.
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http://dx.doi.org/10.1007/s10815-020-02011-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884488PMC
February 2021

Gynecological Cancers Caused by Deficient Mismatch Repair and Microsatellite Instability.

Cancers (Basel) 2020 Nov 10;12(11). Epub 2020 Nov 10.

The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, NY 10021, USA.

Mutations in mismatch repair genes leading to mismatch repair (MMR) deficiency (dMMR) and microsatellite instability (MSI) have been implicated in multiple types of gynecologic malignancies. Endometrial carcinoma represents the largest group, with approximately 30% of these cancers caused by dMMR/MSI. Thus, testing for dMMR is now routine for endometrial cancer. Somatic mutations leading to dMMR account for approximately 90% of these cancers. However, in 5-10% of cases, MMR protein deficiency is due to a germline mutation in the mismatch repair genes , , , , or . These germline mutations, known as Lynch syndrome, are associated with an increased risk of both endometrial and ovarian cancer, in addition to colorectal, gastric, urinary tract, and brain malignancies. So far, gynecological cancers with dMMR/MSI are not well characterized and markers for detection of MSI in gynecological cancers are not well defined. In addition, currently advanced endometrial cancers have a poor prognosis and are treated without regard to MSI status. Elucidation of the mechanism causing dMMR/MSI gynecological cancers would aid in diagnosis and therapeutic intervention. Recently, a new immunotherapy was approved for the treatment of solid tumors with MSI that have recurred or progressed after failing traditional treatment strategies. In this review, we summarize the MMR defects and MSI observed in gynecological cancers, their prognostic value, and advances in therapeutic strategies to treat these cancers.
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http://dx.doi.org/10.3390/cancers12113319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697596PMC
November 2020

Predictive modeling in reproductive medicine: Where will the future of artificial intelligence research take us?

Fertil Steril 2020 11;114(5):934-940

The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, New York.

Artificial intelligence (AI) systems have been proposed for reproductive medicine since 1997. Although AI is the main driver of emergent technologies in reproduction, such as robotics, Big Data, and internet of things, it will continue to be the engine for technological innovation for the foreseeable future. What does the future of AI research look like?
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http://dx.doi.org/10.1016/j.fertnstert.2020.10.040DOI Listing
November 2020

Artificial intelligence in human in vitro fertilization and embryology.

Fertil Steril 2020 11;114(5):914-920

The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, New York.

Embryo evaluation and selection embody the aggregate manifestation of the entire in vitro fertilization (IVF) process. It aims to choose the "best" embryos from the larger cohort of fertilized oocytes, the majority of which will be determined to be not viable either as a result of abnormal development or due to chromosomal imbalances. Indeed, it is generally acknowledged that even after embryo selection based on morphology, time-lapse microscopic photography, or embryo biopsy with preimplantation genetic testing, implantation rates in the human are difficult to predict. Our pursuit of enhancing embryo evaluation and selection, as well as increasing live birth rates, will require the adoption of novel technologies. Recently, several artificial intelligence (AI)-based methods have emerged as objective, standardized, and efficient tools for evaluating human embryos. Moreover, AI-based methods can be implemented for other clinical aspects of IVF, such as assessing patient reproductive potential and individualizing gonadotropin stimulation protocols. As AI has the capability to analyze "big" data, the ultimate goal will be to apply AI tools to the analysis of all embryological, clinical, and genetic data in an effort to provide patient-tailored treatments. In this chapter, we present an overview of existing AI technologies in reproductive medicine and envision their potential future applications in the field.
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http://dx.doi.org/10.1016/j.fertnstert.2020.09.157DOI Listing
November 2020

Artificial intelligence in reproductive medicine: a fleeting concept or the wave of the future?

Authors:
Zev Rosenwaks

Fertil Steril 2020 11;114(5):905-907

Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, New York. Electronic address:

As the world becomes increasingly reliant on computers, it is not surprising that medicine has embraced the computer age with enthusiasm. This is also true in the field of reproductive medicine, where we are witnessing exciting applications of digital technologies and artificial intelligence (AI). It is anticipated that AI-guided approaches will become more objective, more accurate, and more rapid, resulting in greater precision, standardization, and automatization in our field. This month's Views and Reviews contains five thought-provoking contributions addressing the contemporary and futuristic applications of AI in reproductive medicine and the assisted reproductive technologies.
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http://dx.doi.org/10.1016/j.fertnstert.2020.10.002DOI Listing
November 2020

Thoughts on the popularity of ICSI.

J Assist Reprod Genet 2021 Jan 6;38(1):101-123. Epub 2020 Nov 6.

The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, NY, USA.

Purpose: Intracytoplasmic sperm injection (ICSI) is the most widely utilized assisted reproductive technique (ART) worldwide. In this feature, we review the early assisted fertilization attempts that eventually led to the development of ICSI, and discuss its current utilization in cases of male and non-male factor infertility.

Methods: We researched the literature related to the development, indications, and current use of ICSI, such as sperm structural abnormalities, male genetic indications, surgically retrieved sperm, high sperm chromatin fragmentation, oocyte dysmorphism, and preimplantation genetic testing (PGT). We also describe the potential future applications of ICSI.

Results: This review summarizes the early micromanipulation techniques that led to the inception of ICSI. We also explore its current indications, including non-male factor infertility, where its use is more controversial. Finally, we consider the benefits of future advancements in reproductive biology that may incorporate ICSI, such as in vitro spermatogenesis, neogametogenesis, and heritable genome editing.

Conclusion: The versatility, consistency, and reliability of ICSI have made it the most prevalently utilized ART procedure worldwide.
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http://dx.doi.org/10.1007/s10815-020-01987-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823003PMC
January 2021

Prevention of noncommunicable diseases by interventions in the preconception period: A FIGO position paper for action by healthcare practitioners.

Int J Gynaecol Obstet 2020 Sep;151 Suppl 1:6-15

Institute of Developmental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.

With the increase in obesity prevalence among women of reproductive age globally, the risks of type 2 diabetes, gestational diabetes, pre-eclampsia, and other conditions are rising, with detrimental effects on maternal and newborn health. The period before pregnancy is increasingly recognized as crucial for addressing weight management and reducing malnutrition (both under- and overnutrition) in both parents to reduce the risk of noncommunicable diseases (NCDs) in the mother as well as the passage of risk to her offspring. Healthcare practitioners, including obstetricians, gynecologists, midwives, and general practitioners, have an important role to play in supporting women in planning a pregnancy and achieving healthy nutrition and weight before pregnancy. In this position paper, the FIGO Pregnancy Obesity and Nutrition Initiative provides an overview of the evidence for preconception clinical guidelines to reduce the risk of NCDs in mothers and their offspring. It encourages healthcare practitioners to initiate a dialogue on women's health, nutrition, and weight management before conception. While acknowledging the fundamental importance of the wider social and environmental determinants of health, this paper focuses on a simple set of recommendations for clinical practice that can be used even in short consultations. The recommendations can be contextualized based on local cultural and dietary practices as part of a system-wide public health approach to influence the wider determinants as well as individual factors influencing preconception health.
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http://dx.doi.org/10.1002/ijgo.13331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590173PMC
September 2020

Comparison of Human Antral Follicles of Xenograft versus Ovarian Origin Reveals Disparate Molecular Signatures.

Cell Rep 2020 08;32(6):108027

Center for Reproductive Medicine and Infertility, Weill Cornell Medical College, New York, NY 10065, USA; Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY 10065, USA; Tri-Institutional Stem Cell Derivation Laboratory, Weill Cornell Medical College, New York, NY 10065, USA. Electronic address:

The activation, growth, and maturation of oocytes to an ovulatory phase, termed folliculogenesis, is governed by the orchestrated activity of multiple specialized cell types within the ovary; yet, the mechanisms governing diversification and behavior of discrete cellular sub-populations within follicles are poorly understood. We use bulk and single-cell RNA sequencing to distinguish the transcriptional signature of prospectively isolated granulosa and theca/stroma cell subsets within human antral follicles derived from xenografts or ovaries. The analysis deconstructs phenotypic diversification within small (<4 mm) antral follicles, identifying secreted factors that are differentially enriched between mural and oophorus granulosa cells, and segregating stromal/support and steroidal activity between theca externa and interna, respectively. Multiple factors are differentially expressed in follicles of xenograft versus ovarian origin. These data capture a high-resolution transcriptional signature of granulosa and theca subpopulations and provide a systems-level portrait of cellular diversification in early antral human follicles.
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http://dx.doi.org/10.1016/j.celrep.2020.108027DOI Listing
August 2020

Identification and treatment of men with phospholipase Cζ-defective spermatozoa.

Fertil Steril 2020 09 23;114(3):535-544. Epub 2020 Jul 23.

Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, New York. Electronic address:

Objective: To identify and treat the gamete responsible for complete fertilization failure with intracytoplasmic sperm injection (ICSI) using a newly proposed assisted gamete treatment (AGT).

Design: Prospective cohort study.

Setting: Center for reproductive medicine.

Patient(s): One-hundred and fourteen couples with an adequate number of spermatozoa for ICSI and a fertilization rate of ≤10%, after controlling for maternal age.

Intervention(s): Couples with an oocyte-related oocyte activation deficiency (OAD) underwent a subsequent cycle with a modified superovulation protocol; couples with sperm-related OAD had an additional genetic and epigenetic assessment to identify mutations and expression levels of the corresponding genes.

Main Outcome Measure(s): Treatment cycle outcome for couples undergoing ICSI with either a modified superovulation protocol or AGT compared with their historical cycle.

Result(s): A total of 114 couples matched the inclusion criteria, representing approximately 1.3% of the total ICSI cycles performed at our center, with age-matched controls. Fifty-two couples were confirmed negative for sperm-related OAD by the phospholipase Cζ (PLCζ) assay, indicating oocyte-related factors in their failed fertilization cycles. Couples were treated by one of two AGT protocols, AGT-initial or AGT-revised, in a subsequent attempt that was compared with their historical cycle. Subsequent ICSI cycles with a tailored superovulation protocol yielded significantly higher fertilization (59.0% vs. 2.1%) and clinical pregnancy (28.6% vs. 0) rates. In 24 couples (mean ± standard deviation: maternal age, 35.6 ± 5 years; paternal age, 39.8 ± 6 years) sperm-related OAD was confirmed; in four men, a deletion on the PLCZ1 gene was identified. Additional mutations were also identified of genes supporting spermiogenesis and embryo development (PIWIL1, BSX, NLRP5) and gene deletions confirming a complete absence of the subacrosomal perinuclear theca (PICK1, SPATA16, DPY19L). Subsequent AGT treatment provided higher fertilization (42.1%) and clinical pregnancy (36% vs. 0%) rates for couples with a history of impaired (9.1%) fertilization. A comparison of the two AGT protocols, AGT-initial or AGT-revised, revealed that the latter yielded even more favorable fertilization (37.6% vs. 45.9%) and clinical pregnancy (21.1% vs. 83.3%) rates.

Conclusion(s): In couples with an oocyte-related OAD, tailoring the superovulation protocol resulted in successful fertilization, term pregnancies, and deliveries. In couples with a sperm-related OAD as determined by PLCζ assay, mouse oocyte activation test, and the assessment of gene mutations and function, AGT was successful. The AGT-revised protocol yielded an even higher fertilization rate than the AGT-initial protocol, resulting in the birth of healthy offspring in all couples who achieved a clinical pregnancy.
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http://dx.doi.org/10.1016/j.fertnstert.2020.04.044DOI Listing
September 2020

Pluripotent stem cells with low differentiation potential contain incompletely reprogrammed DNA replication.

J Cell Biol 2020 09;219(9)

The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, NY.

Reprogrammed pluripotent stem cells (PSCs) are valuable for research and potentially for cell replacement therapy. However, only a fraction of reprogrammed PSCs are developmentally competent. Genomic stability and accurate DNA synthesis are fundamental for cell development and critical for safety. We analyzed whether defects in DNA replication contribute to genomic instability and the diverse differentiation potentials of reprogrammed PSCs. Using a unique single-molecule approach, we visualized DNA replication in isogenic PSCs generated by different reprogramming approaches, either somatic cell nuclear transfer (NT-hESCs) or with defined factors (iPSCs). In PSCs with lower differentiation potential, DNA replication was incompletely reprogrammed, and genomic instability increased during replicative stress. Reprogramming of DNA replication did not correlate with DNA methylation. Instead, fewer replication origins and a higher frequency of DNA breaks in PSCs with incompletely reprogrammed DNA replication were found. Given the impact of error-free DNA synthesis on the genomic integrity and differentiation proficiency of PSCs, analyzing DNA replication may be a useful quality control tool.
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http://dx.doi.org/10.1083/jcb.201909163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480103PMC
September 2020

Primum non nocere: in vitro fertilization in the epicenter.

Fertil Steril 2020 08 9;114(2):219-220. Epub 2020 Jul 9.

Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, New York, New York.

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http://dx.doi.org/10.1016/j.fertnstert.2020.06.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833459PMC
August 2020

Incarcerated Omental Hernia at a 5-mm Trocar Site after Laparoscopy.

J Minim Invasive Gynecol 2021 03 9;28(3):384-385. Epub 2020 Jul 9.

The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine (Drs. Pereira, Irani, Chung, and Rosenwaks, and Mr. Chung), Weill Cornell Medicine, New York, New York.

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http://dx.doi.org/10.1016/j.jmig.2020.07.003DOI Listing
March 2021

Tubal Ectopic Pregnancy with Undetectable Initial Serum β-Human Chorionic Gonadotropin Level.

J Minim Invasive Gynecol 2021 01 26;28(1):142-145. Epub 2020 Jun 26.

The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine (Drs. Pereira, Romanski, Kligman, Rosenwaks, and Ms. Wright), Weill Cornell Medicine, New York, New York.

We present a case of a tubal ectopic pregnancy (EP) in a patient with an initially undetectable serum β-human chorionic gonadotropin (β-hCG) level. A 33-year-old woman in a same-sex relationship underwent timed donor intrauterine insemination. Her serum β-hCG level was <5 mIU/mL 14 days after the intrauterine insemination. She reported menstrual bleeding 3 days after her negative pregnancy test and returned to the office 10 days later to begin a new treatment cycle. Her serum levels of estradiol, progesterone, and β-hCG were 119 pg/mL, 6.1 ng/mL and 1157 mIU/mL, respectively. Transvaginal ultrasonography did not show an intrauterine pregnancy. Her β-hCG level increased to 1420 mIU/mL the next day. She was diagnosed with a pregnancy of unknown location and treated with methotrexate. Her β-hCG levels continued to increase despite 3 methotrexate doses, necessitating laparoscopy. The diagnostic laparoscopy demonstrated approximately 100 mL of hemoperitoneum in the posterior cul-de-sac with an intact right fallopian tube that was dilated at its distal end by the EP. A total right salpingectomy was performed. Her β-hCG level was <5 mIU/mL 3 weeks later. The current case supports that although rare, an undetectable serum β-hCG level does not completely rule out the diagnosis of an EP.
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http://dx.doi.org/10.1016/j.jmig.2020.06.015DOI Listing
January 2021

Delay in IVF treatment up to 180 days does not affect pregnancy outcomes in women with diminished ovarian reserve.

Hum Reprod 2020 07;35(7):1630-1636

Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, New York, NY, USA.

Study Question: Will a delay in initiating IVF treatment affect pregnancy outcomes in infertile women with diminished ovarian reserve?

Summary Answer: A delay in IVF treatment up to 180 days does not affect the live birth rate for women with diminished ovarian reserve when compared to women who initiate IVF treatment within 90 days of presentation.

What Is Known Already: In clinical practice, treatment delays can occur due to medical, logistical or financial reasons. Over a period of years, a gradual decline in ovarian reserve occurs which can result in declining outcomes in response to IVF treatment over time. There is disagreement among reproductive endocrinologists about whether delaying IVF treatment for a few months can negatively affect patient outcomes.

Study Design, Size, Duration: A retrospective cohort study of infertile patients in an academic hospital setting with diminished ovarian reserve who started an IVF cycle within 180 days of their initial consultation and underwent an oocyte retrieval with planned fresh embryo transfer between 1 January 2012 and 31 December 2018.

Participants/materials, Setting, Methods: Diminished ovarian reserve was defined as an anti-Müllerian hormone (AMH) <1.1 ng/ml. In total, 1790 patients met inclusion criteria (1115 immediate and 675 delayed treatment). Each patient had one included cycle and no subsequent data from additional frozen embryo transfer cycles were included. Since all cycle outcomes evaluated were from fresh embryo transfers, no genetically tested embryos were included. Patients were grouped by whether their cycle started 1-90 days after presentation (immediate) or 91-180 days (delayed). The primary outcome was live birth (≥24 weeks of gestation). A subgroup analysis of more severe forms of diminished ovarian reserve was performed to evaluate outcomes for patients with an AMH <0.5 and for patients >40 years old with an AMH <1.1 ng/ml (Bologna criteria for diminished ovarian reserve). Logistic regression analysis, adjusted a priori for patient age, was used to estimate the odds ratio (OR) with a 95% CI. All pregnancy outcomes were additionally adjusted for the number of embryos transferred.

Main Results And The Role Of Chance: The mean ± SD number of days from presentation to IVF start was 50.5 ± 21.9 (immediate) and 128.8 ± 25.9 (delayed). After embryo transfer, the live birth rate was similar between groups (immediate: 23.9%; delayed: 25.6%; OR 1.08, 95% CI 0.85-1.38). Additionally, a similar live birth rate was observed in a subgroup analysis of patients with an AMH <0.5 ng/ml (immediate: 18.8%; delayed: 19.1%; OR 0.99, 95% CI 0.65-1.51) and in patients >40 years old with an AMH <1.1 ng/ml (immediate: 12.3%; delayed: 14.7%; OR 1.21, 95% CI 0.77-1.91).

Limitations, Reasons For Caution: There is the potential for selection bias with regard to the patients who started their IVF cycle within 90 days compared to 91-180 days after initial consultation. In addition, we did not include patients who were seen for initial evaluation but did not progress to IVF treatment with oocyte retrieval; therefore, our results should only be applied to patients with diminished ovarian reserve who complete an IVF cycle. Finally, since we excluded patients who started their IVF cycle greater than 180 days from their first visit, it is not known how such a delay in treatment affects pregnancy outcomes in IVF cycles.

Wider Implications Of The Findings: A delay in initiating IVF treatment in patients with diminished ovarian reserve up to 180 days from the initial visit does not affect pregnancy outcomes. This observation remains true for patients who are in the high-risk categories for poor response to ovarian stimulation. Providers and patients should be reassured that when a short-term treatment delay is deemed necessary for medical, logistic or financial reasons, treatment outcomes will not be affected.

Study Funding/competing Interest(s): No financial support, funding or services were obtained for this study. The authors do not report any potential conflicts of interest.

Trial Registration Number: Not applicable.
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http://dx.doi.org/10.1093/humrep/deaa137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337822PMC
July 2020

Multicentric, prospective observational data show sperm capacitation predicts male fertility, and cohort comparison reveals a high prevalence of impaired capacitation in men questioning their fertility.

Reprod Biomed Online 2020 Jul 1;41(1):69-79. Epub 2020 May 1.

Park Nicollet Sexual Medicine & Male Infertility Clinic, St Louis Park MN, USA.

Research Questions: Can a previously defined relationship between sperm capacitation and the probability of a man generating pregnancy within three cycles, prospectively predict male fertility in diverse clinical settings? A second study asked, what is the prevalence of impaired sperm fertilizing ability in men questioning their fertility (MQF), and does this relate to traditional semen analysis metrics?

Design: In the multicentric, prospective observational study, data (n = 128; six clinics) were analysed to test a published relationship between the percentage of fertilization-competent, capacitated spermatozoa (Cap-Score) and probability of generating pregnancy (PGP) within three cycles of intrauterine insemination. Logistic regression of total pregnancy outcomes (n = 252) assessed fit. In the cohort comparison, Cap-Scores of MQF (n = 2155; 22 clinics) were compared with those of 76 fertile men.

Results: New outcomes (n = 128) were rank-ordered by Cap-Score and divided into quintiles (25-26 per group); chi-squared testing revealed no difference between predicted and observed pregnancies (P = 0.809). Total outcomes (n = 252; 128 new + 124 previous) were pooled and the model recalculated, yielding an improved fit (P < 0.001). Applying the Akaike information criterion found that the optimal model used Cap-Score alone. Cap-Scores were performed on 2155 men (with semen analysis data available for 1948). To compare fertilizing ability, men were binned by PGP (≤19%, 20-29%, 30-39%, 40-49%, 50-59%, ≥60%). Distributions of PGP and the corresponding Cap-Scores were significantly lower in MQF versus fertile men (P < 0.001). Notably, 64% of MQF with normal volume, concentration and motility (757/1183) had PGP of 39% or less (Cap-Scores ≤31), versus 25% of fertile men.

Conclusions: Sperm capacitation prospectively predicted male fertility. Impaired capacitation affects many MQF with normal semen analysis results, informing diagnosis versus idiopathic infertility.
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http://dx.doi.org/10.1016/j.rbmo.2020.03.011DOI Listing
July 2020