Characterization of CRESS-DNA viruses in human vaginal secretions: An exploratory metagenomic investigation.

The Phylum Cressdnaviricota consists of a large number of circular Rep-encoding single-stranded (CRESS)-DNA viruses. Recently, metagenomic analyzes revealed their ubiquitous distribution in a diverse range of eukaryotes. Data relating to CRESS-DNA viruses in humans remains scarce. Our study investigated the presence and genetic diversity of CRESS-DNA viruses in human vaginal secretions. Vaginal swabs were collected from 28 women between 29 and 43 years old attending a fertility clinic in New York City. An exploratory metagenomic analysis was performed and detection of CRESS-DNA viruses was confirmed through analysis of near full-length sequences of the viral isolates. A phylogenetic tree was based on the REP open reading frame sequences of the CRESS-DNA virus genome. Eleven nearly complete CRESS-DNA viral genomes were identified in 16 (57.1%) women. There were no associations between the presence of these viruses and any demographic or clinical parameters. Phylogenetic analysis indicated that one of the sequences belonged to the genus Gemycircularvirus within the Genomoviridae family, while ten sequences represented previously unclassified species of CRESS-DNA viruses. Novel species of CRESS-DNA viruses are present in the vaginal tract of adult women. Although they be transient commensal agents, the potential clinical implications for their presence at this site cannot be dismissed.

Combining early pregnancy bleeding with ultrasound measurements to assess spontaneous abortion risk among infertile patients.

BACKGROUND: Approximately 15% of all clinically recognized pregnancies in patients with infertility result in spontaneous abortion. However, despite its potential to have a profound and lasting effect on physical and emotional well-being, the natural history of spontaneous abortion in women with infertility has not been described. Although vaginal bleeding is a common symptom in pregnancies conceived via reproductive technologies, its prognostic value is not well understood. OBJECTIVE: This study aimed to evaluate the combination of early pregnancy bleeding and first-trimester ultrasound measurements to determine spontaneous abortion risk. STUDY DESIGN: This was a retrospective cohort study of patients with infertility who underwent autologous embryo transfer resulting in singleton intrauterine pregnancy confirmed by ultrasound from January 1, 2017, to December 31, 2019. Early pregnancy symptoms of bleeding occurring before gestational week 8 and measurements of crown-rump length and fetal heart rate from ultrasounds performed during gestational week 6 (6 0/7 to 6 6/7 weeks of gestation) and gestational week 7 (7 0/7 to 7 6/7 weeks of gestation) were recorded. Modified Poisson regression with robust error variance was adjusted a priori for patient age, embryo transfer day, and transfer of a preimplantation genetic-tested embryo to estimate the relative risk and 95% confidence interval of spontaneous abortion for dichotomous variables. The relative risks and positive predictive values for early pregnancy bleeding combined with ultrasound measurements on the occurrence of spontaneous abortion were calculated for patients who had an ultrasound performed during gestational week 6 and separately for patients who had an ultrasound performed during gestational week 7. The primary outcome was spontaneous abortion in the setting of vaginal bleeding with normal ultrasound parameters. The secondary outcomes were spontaneous abortion with vaginal bleeding and (1) abnormal crown-rump length, (2) abnormal fetal heart rate, and (3) both abnormal crown-rump length and abnormal fetal heart rate. RESULTS: Of the 1858 patients who were included (359 cases resulted in abortions and 1499 resulted in live births), 315 patients (17.0%) reported vaginal bleeding. When combined with ultrasound measurements from gestational week 6, bleeding was significantly associated with increased spontaneous abortion only when accompanied by absent fetal heart rate (relative risk, 5.36; 95% confidence interval, 3.36-8.55) or both absent fetal heart rate and absent fetal pole (relative risk, 9.67; 95% confidence interval, 7.45-12.56). Similarly, when combined with ultrasound measurements from gestational week 7, bleeding was significantly associated with increased spontaneous abortion only when accompanied by an abnormal assessment of fetal heart rate or crown-rump length (relative risk, 5.09; 95% confidence interval, 1.83-14.19) or both fetal heart rate and crown-rump length (relative risk, 14.82; 95% confidence interval, 10.54-20.83). With normal ultrasound measurements, bleeding was not associated with increased spontaneous abortion risk (relative risk: 1.05 [95% confidence interval, 0.61-1.78] in gestational week 6 and 0.80 [95% confidence interval, 0.36-1.74] in gestational week 7), and the live birth rate was comparable with that in patients with normal ultrasound measurements and no bleeding. CONCLUSION: Patients with a history of infertility who present after embryo transfer with symptoms of vaginal bleeding should be evaluated with a pregnancy ultrasound to accurately assess spontaneous abortion risk. In the setting of normal ultrasound measurements, patients can be reassured that their risk of spontaneous abortion is not increased and that their live birth rate is not decreased.

Live birth outcomes are not associated with household income and insurance disparities following ART treatment.

RESEARCH QUESTION: Is household income or IVF insurance coverage associated with live birth outcomes in infertile women undertaking IVF? DESIGN: Retrospective cohort study in an academic hospital, including patients residing in New York State undergoing a frozen single embryo transfer at the study IVF centre between 1 January 2017 and 31 December 2018. Only the first embryo transfer per patient was included. Patients were stratified by tertiles of estimated income using home zip code census data: <$85,888 (n = 348), $85,888-122,628 (n = 348) and >$122,628 (n = 350). A second analysis stratified patients by IVF insurance coverage or no coverage. The primary outcome was live birth. Modified Poisson regression with robust error variance adjusted a priori for age, preimplantation genetic testing and previous fresh embryo transfer estimated the relative risk of outcomes with a 95% confidence interval. RESULTS: A total of 1046 patients were included. Live birth rate was similar among all three income tertiles. Secondarily, the pregnancy rate and pregnancy loss rate were also similar among all three tertiles. In the IVF insurance coverage analysis, live birth rate was similar between patients with and without IVF insurance coverage. Secondarily, the pregnancy rate and pregnancy loss rate were also similar among these two groups. CONCLUSION: Overall, neither median household income nor IVF insurance coverage of patients undergoing single frozen embryo transfer was associated with pregnancy, pregnancy loss or live birth outcomes. Lower income, relative to the patient cohort, and lack of insurance coverage are well-described barriers to accessing infertility evaluation and treatment. However, once treatment is initiated, the current results suggest that these variables do not influence pregnancy and live birth outcomes in infertile patients.

Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline Part I.

PURPOSE: The summary presented herein represents Part I of the two-part series dedicated to the Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline. Part I outlines the appropriate evaluation of the male in an infertile couple. Recommendations proceed from obtaining an appropriate history and physical exam (Appendix I), as well as diagnostic testing, where indicated. MATERIALS/METHODS: The Emergency Care Research Institute Evidence-based Practice Center team searched PubMed®, Embase®, and Medline from January, 2000 through May, 2019. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table 1[Table: see text]). This summary is being simultaneously published in Fertility and Sterility and The Journal of Urology. RESULTS: This Guideline provides updated, evidence-based recommendations regarding evaluation of male infertility as well as the association of male infertility with other important health conditions. The detection of male infertility increases the risk of subsequent development of health problems for men. In addition, specific medical conditions are associated with some causes for male infertility. Evaluation and treatment recommendations are summarized in the associated algorithm (figure[Figure: see text]). CONCLUSION: The presence of male infertility is crucial to the health of patients and its effects must be considered for the welfare of society. This document will undergo updating as the knowledge regarding current treatments and future treatment options continues to expand.

Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline PART II.

PURPOSE: The summary presented herein represents Part II of the two-part series dedicated to the Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline. Part II outlines the appropriate management of the male in an infertile couple. Medical therapies, surgical techniques, as well as use of intrauterine insemination (IUI)/in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) are covered to allow for optimal patient management. Please refer to Part I for discussion on evaluation of the infertile male and discussion of relevant health conditions that are associated with male infertility. MATERIALS/METHODS: The Emergency Care Research Institute Evidence-based Practice Center team searched PubMed®, Embase®, and Medline from January 2000 through May 2019. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table[Table: see text]). This summary is being simultaneously published in Fertility and Sterility and The Journal of Urology. RESULTS: This Guideline provides updated, evidence-based recommendations regarding management of male infertility. Such recommendations are summarized in the associated algorithm (figure[Figure: see text]). CONCLUSION: Male contributions to infertility are prevalent, and specific treatment as well as assisted reproductive techniques are effective at managing male infertility. This document will undergo additional literature reviews and updating as the knowledge regarding current treatments and future treatment options continues to expand.

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

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/m2) and a mildly underweight group (BMI 17.5-18.49 kg/m2), and were compared with a normal-weight group (BMI 18.5-24.9 kg/m2). 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.

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

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.

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

OBJECTIVE: Assess the effect of class III (body mass index [BMI, kg/m2] 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.

Insulin-like growth factor-1 and soluble FMS-like tyrosine kinase-1 prospectively predict cancelled IVF cycles.

PURPOSE: To identify biomarkers that prospectively predict IVF cycle cancellation. METHODS: In this prospective study, sera were obtained prior to any intervention, from women about to undergo an IVF cycle. The sera were assayed by ELISA for levels of insulin-like growth factor (IGF)-1, IGF-2, IGF binding protein (BP)-1, and soluble fms-like tyrosine kinase (sFLT-1). The cancellation or progression of the IVF cycle was subsequently obtained by chart review. Associations between serum components and outcome were analyzed by the Mann-Whitney test. Receiver operator curves were constructed to evaluate the strength of the correlations between biomarkers and cycle cancellation, as assessed from the area under the curve (AUC). RESULTS: A total of 205 women were included. Twenty-seven (13.2%) cycle cancellations due to poor response were recorded. Women with a cancelled cycle had reduced anti-Mullerian hormone (AMH) values (p < 0.001) and antral follicle count (p = 0.003). There were no significant differences between the two groups with regard to age and BMI. Median concentrations of IGF-1 and sFLT-1 were elevated in sera from women whose IVF cycles were cancelled as compared to those with ongoing cycles (p = 0.015 and p < 0.001, respectively); AUC for IGF-1 and sFLT-1 were 0.67 and 0.75, respectively. Concentrations of sFLT-1 remained significantly higher in patients with cancelled cycles even after controlling for AMH levels. There were no differences in IGF-2 and IGFBP-1 levels between the two groups. CONCLUSIONS: Measurement of circulating IGF-1 and sFLT-1 levels prior to initiation of an IVF cycle has the potential to identify women whose cycles have an increased likelihood to be subsequently cancelled.

Unilateral Salpingectomy and Methotrexate Are Associated With a Similar Recurrence Rate of Ectopic Pregnancy in Patients Undergoing In Vitro Fertilization.

STUDY OBJECTIVE: To determine whether different treatment approaches of ectopic pregnancy (EP), particularly unilateral salpingectomy and methotrexate, affect its recurrence rate in patients undergoing in vitro fertilization (IVF). DESIGN: A retrospective cohort study (Canadian Task Force classification II-2). SETTING: An academic medical center. PATIENTS: Patients with a history of a previous EP who achieved pregnancy after IVF cycles between January 2004 and August 2015 were included. The recurrence rate of EP was compared between patients who underwent different treatment approaches for a previous EP. INTERVENTIONS: IVF. MEASUREMENTS AND MAIN RESULTS: A total of 594 patients were included. Seventeen patients had a recurrence of EP (2.9%). Patients with a history of ≥2 EPs were associated with a significantly higher recurrence rate of EP than those with 1 previous EP (8.5% vs. 1.8%; p = .01; odds ratio [OR] = 2.2; 95% confidence interval [CI], 1.2-4.4). Patients who underwent unilateral salpingectomy (n = 245) had a comparable recurrence rate of EP after IVF with those who received methotrexate (n = 283) (3.6% vs. 2.8%; p = .5; OR = 1.3; 95% CI, 0.4-3.4). This OR remained unchanged after adjusting for patient's age, number of previous EPs, number of transferred embryos, and peak estradiol level during stimulation (adjusted OR = 1.4; 95% CI, 0.5-3.8). None of the patients who underwent bilateral salpingectomy (n = 45) or salpingostomy (n = 21) had a recurrence of EP after IVF. CONCLUSION: The recurrence rate of EP significantly correlates with the number of previous EPs. Treatment of EP with methotrexate has a comparable recurrence rate of EP after IVF with unilateral salpingectomy. Therefore, the risk of recurrence should not be a reason to favor salpingectomy over methotrexate in this population.

Ovarian Response and in Vitro Fertilization Outcomes After Salpingectomy: Does Salpingectomy Indication Matter?

STUDY OBJECTIVE: To investigate whether the ovarian response and pregnancy outcomes of patients undergoing in vitro fertilization (IVF) after salpingectomy are affected by the underlying indication for salpingectomy. DESIGN: Retrospective cohort study (Canadian Task Force classification II-3). SETTING: University-affiliated fertility center. PATIENTS: All patients age <37 years undergoing IVF within 12 months of laparoscopic salpingectomy. The underlying indication for laparoscopic salpingectomy in the study cohort was tubal ectopic pregnancy, unilateral or bilateral hydrosalpinx, or other reason (hematosalpinx or pyosalpinx), as confirmed by histopathology. INTERVENTIONS: IVF and embryo transfer (ET). MEASUREMENTS AND MAIN RESULTS: Surgical characteristics, demographics, ovarian stimulation parameters, total oocytes retrieved, fertilization rates, implantation rates, and clinical pregnancy rates were compared among the salpingectomy groups. Age- and time-matched patients undergoing their first IVF-ET cycle for male factor infertility, with no previous history of laparoscopy, served as controls. RESULTS: Of the 996 patients who underwent a laparoscopic procedure during the study period, 136 patients underwent unilateral salpingectomy for the following indications: 39 for ectopic pregnancy, 81 for unilateral hydrosalpinx, and 16 for other indications. Among these 136 patients, 29 in the ectopic pregnancy group, 75 in the unilateral hydrosalpinx group, and 10 in the "other" group underwent subsequent IVF-ET. Thirty-one patients underwent both bilateral salpingectomy and subsequent IVF-ET. There was no difference in the antral follicle counts before and after salpingectomy in all groups. There was a statistically significant difference in the mean duration of ovarian stimulation in the salpingectomy groups: ectopic pregnancy, 10.9 ± 2.15 days; unilateral hydrosalpinx, 9.56 ± 1.95 days; bilateral hydrosalpinx, 9.51 ± 2.01 days; "other", 9.89 ± 2.20 days; control, 9.76 ± 1.99 days. Similar trends were noted for total gonadotropins administered when comparing the ectopic pregnancy group (3375.9 ± 931.0 IU) with the remaining groups (unilateral hydrosalpinx, 2841.3 ± 1160.9 IU; bilateral hydrosalpinx, 2519.3 ± 1004.7 IU; "other", 2808.6 ± 990.1 IU; control, 2726.1 ± 1129.8 IU). There were no significant differences in the total number of oocytes retrieved, fertilization rate, implantation rate, or clinical pregnancy rate in the salpingectomy groups compared with controls. CONCLUSION: Although our findings indicate that patients undergoing IVF after salpingectomy for an ectopic pregnancy have a statistically significantly longer duration of stimulation and require higher gonadotropin doses compared with patients undergoing IVF after salpingectomy for other indications, these differences are of limited clinical significance, given that the total number of oocytes retrieved, implantation rate, and clinical pregnancy rate among the different salpingectomy groups are comparable to those in controls.

Replacing single frozen-thawed euploid embryos in a natural cycle in ovulatory women may increase live birth rates compared to medicated cycles in anovulatory women.

PURPOSE: The goal of this study was to compare pregnancy outcomes between natural frozen embryo transfer (FET) cycles in ovulatory women and programmed FET cycles in anovulatory women after undergoing in vitro fertilization with preimplantation genetic screening (IVF-PGS). METHODS: This was a retrospective cohort study performed at an academic medical center. Patients undergoing single FET IVF-PGS cycles between October 2011 and December 2014 were included. Patients were stratified by type of endometrial replacement: programmed cycles with estrogen/progesterone replacement and natural cycles. IVF-PGS with 24-chromosome screening was performed on all included patients. Those patients with euploid embryos had single embryo transfer in a subsequent FET. The primary study outcome was live birth/ongoing pregnancy rate. Secondary outcomes included implantation, biochemical pregnancy, and miscarriage rates. RESULTS: One hundred thirteen cycles met inclusion criteria: 65 natural cycles and 48 programmed cycles. The programmed FET group was younger (35.9 ± 4.5 vs. 37.5 ± 3.7, P = 0.03) and had a higher AMH (3.95 ± 4.2 vs. 2.37 ± 2.4, P = 0.045). The groups were similar for BMI, gravidity, parity, history of uterine surgery, and incidence of Asherman's syndrome. There was also no difference in embryo grade at biopsy or transfer, and proportion of day 5 and day 6 transfers. Implantation rates were higher in the natural FET group (0.66 ± 0.48 vs. 0.44 ± 0.50, P = 0.02). There was no difference in the rates of biochemical pregnancy or miscarriage. After controlling for age, live birth/ongoing pregnancy rate was higher in natural FETs with an adjusted odds ratio of 2.68 (95% CI 1.22-5.87). CONCLUSIONS: Natural FET in ovulatory women after IVF-PGS is associated with increased implantation and live birth rates compared to programmed FET in anovulatory women. Further investigation is needed to determine whether these findings hold true in other patient cohorts.

Association of in vitro fertilization outcome with circulating insulin-like growth factor components prior to cycle initiation.

OBJECTIVE: Components of the insulin-like growth factor (IGF) system enhance in vitro embryo quality and implantation rates in both animal models and human in vitro fertilization (IVF). We evaluated whether differences in serum levels of these components in women prior to initiation of an IVF cycle would be predictive of subsequent outcome. STUDY DESIGN: In this retrospective study sera from women obtained at day 2 of their IVF cycle (at baseline before stimulation) were assayed for IGF-I, IGF-II, and IGF binding protein (BP)-1 by enzyme-linked immunosorbent assay. Samples from 54 women with a live birth, 38 with a transient biochemical pregnancy, 45 with a spontaneous abortion, 54 who did not become pregnant, and 35 who had an ectopic pregnancy were available for analysis. Associations between the assays and outcome were evaluated by the Kruskal-Wallis test and receiver operating characteristic analysis. RESULTS: There were no differences in the number of oocytes retrieved, oocyte quality, fertilization rates, or embryo grade between groups. Median concentrations of IGF-I were elevated in women with a live birth (29.1 ng/mL) as compared to women with a biochemical pregnancy (25.6 ng/mL), with spontaneous abortion (21.2 ng/mL), who were not pregnant (18.7 pg/mL), or who had an ectopic pregnancy (4.2 pg/mL) (P < .001). Conversely, median levels of IGF-II were reduced in women with a live birth (294.5 ng/mL) as opposed to 357.5, 393.6, 407.2, and 426.9 ng/mL in women with a biochemical pregnancy, with ectopic pregnancy, with spontaneous abortion, or who were not pregnant, respectively (P < .001). Median IGFBP-1 concentrations were markedly elevated in women with a live birth (23.6 ng/mL) compared to 18.3, 14.1, 13.8, and 9.5 ng/mL in women with a biochemical pregnancy, with spontaneous abortion, who were not pregnant, or with an ectopic pregnancy (P < .001). The combination of IGF-I and IGFBP-1 best predicted the occurrence of a live birth with an area under the curve of 0.892. CONCLUSION: Maternal serum levels of IGF-I, IGF-II, and IGFBP-1 prior to initiation of an IVF cycle are correlated with the likelihood of a live birth. Alterations in maternal IGF system components may influence oocyte quality or the success of early postfertilization events and embryo implantation.

Impact of newly diagnosed endometrial polyps during controlled ovarian hyperstimulation on in vitro fertilization outcomes.

STUDY OBJECTIVE: To investigate the impact of newly diagnosed endometrial polyps during controlled ovarian hyperstimulation (COH) on the outcomes of fresh in vitro fertilization (IVF)-embryo transfer (ET) cycles. DESIGN: A retrospective cohort study (Canadian Task Force classification II-3). SETTING: An academic center. PATIENTS: All patients initiating IVF cycles at the Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine during a 1-year period. Patients were stratified into 2 groups based on the presence or absence of newly diagnosed endometrial polyps during COH. INTERVENTIONS: IVF with fresh ET. MEASUREMENTS AND MAIN RESULTS: Two thousand nine hundred ninety-three patients were identified: 60 in the polyp group and 2933 in the nonpolyp group. The overall positive pregnancy, clinical pregnancy, spontaneous miscarriage, and live birth rates were similar between the groups. The biochemical pregnancy rate was 18.3% in the polyp group compared with 9.6% in the nonpolyp group (p = .01). This represented a 2-fold increased odds of biochemical pregnancy in the polyp group (odds ratio = 2.12; 95% confidence interval, 1.09-4.12) compared with the nonpolyp group. CONCLUSION: Newly diagnosed endometrial polyps during COH is associated with an increased biochemical pregnancy rate but ultimately does not adversely impact clinical pregnancy or live birth rates after fresh IVF-ET.

Effect of Methotrexate or Salpingectomy for Ectopic Pregnancy on Subsequent In Vitro Fertilization-Embryo Transfer Outcomes.

OBJECTIVE: To investigate the effect of methotrexate (MTX) or salpingectomy for ectopic pregnancy on the outcomes of subsequent in vitro fertilization (IVF)-embryo transfer (ET) cycles. DESIGN: Retrospective cohort study (Canadian Task Force Classification II-3). SETTING: Academic center. PATIENTS: All patients undergoing fresh IVF-ET between January 2004 and July 2013 after treatment of an ectopic pregnancy with MTX or salpingectomy in the preceding IVF-ET cycle were analyzed for potential inclusion. INTERVENTION: MTX or laparoscopic salpingectomy for an ectopic pregnancy followed by a subsequent IVF-ET cycle. MEASUREMENTS AND MAIN RESULTS: A total of 144 patients with sonographically confirmed ectopic pregnancies were identified during the study period. Of these, 107 (74.3%) patients were treated with MTX and 37 (25.7%) were treated with laparoscopic salpingectomy. Eighty-eight patients (82.2%) in the MTX group and 22 patients (59.4%) patients in the salpingectomy group underwent a subsequent IVF-ET cycle. There were no significant differences in demographic data or baseline cycle characteristics between the 2 groups. No difference was observed in basal follicle-stimulating hormone (FSH) level before and after MTX or salpingectomy treatment. Indicators of ovarian responsiveness, including total days of stimulation, total dosage of gonadotropins, and number of mature oocytes before and after either treatment, were comparable in the 2 groups. The number of doses of MTX (1 vs > 1) did not correlate with changes in ovarian response. The pregnancy outcomes, specifically live birth, were equivalent in the 2 groups. Comparing post-MTX cycles and post-salpingectomy cycles, patients in the latter group required higher doses of gonadotropins (+705 IU vs +221.5 IU; p < .01), although the number of mature oocytes remained similar in the 2 groups. CONCLUSION: Treatment of ectopic pregnancies with MTX or salpingectomy might not adversely affect ovarian reserve, ovarian responsiveness, or subsequent IVF cycle outcomes. However, in our study cohort, patients treated with MTX, those s treated with laparoscopic salpingectomy required higher gonadotropin doses in a subsequent cycle to attain the same number of mature oocytes.

Prognostic value of growth of 4-cell embryos on the day of transfer in fresh IVF-ET cycles.

PURPOSE: To investigate the prognostic value of growth of 4-cell embryos on the day of transfer in determining clinical pregnancy and live birth rates after fresh in vitro fertilization (IVF)-embryo transfer (ET) cycles. METHODS: Retrospective cohort study of all patients between January 2008 and January 2013 initiating fresh IVF-ET cycles resulting in embryos that were not more than 4 cells 72 h after oocyte retrieval in the morning of their transfer. Patients were stratified into 2 groups based on whether embryos did or did not grow more than the 4-cell stage on the afternoon of ET. The odds of clinical pregnancy and live birth were considered as primary outcomes. Student's t-tests and Chi-square (χ2) tests were used as indicated, with logistic regression controlling for maternal age and number of embryos transferred. RESULTS: Three hundred forty three patients were identified for inclusion: 165 and 178 patients had 4-cell embryos with and without growth on the afternoon of ET, respectively. The demographic and baseline IVF cycle characteristics of the study cohort were comparable. Patients with embryo growth had higher clinical pregnancy (13.9 % vs. 4.49 %) and live birth (10.9 % vs. 3.37 %) rates compared to patients without embryo growth. This represented an overall increased odds of clinical pregnancy [Odds ratio (OR) = 3.44; 95 % Confidence Intervals (CI) 1.49-7.93; P = 0.004)] and live birth (OR = 3.51; 95 % CI 1.36-9.07; P = 0.01). The increased odds remained unchanged after adjusting for maternal age and number of embryos transferred. CONCLUSIONS: Transfer of 4-cell embryos 3 days after oocyte retrieval can result in clinical pregnancies and live births, albeit at a low rate. Growth of an embryo more than the 4-cell stage on the afternoon of ET may serve as a positive prognostic factor for IVF-ET cycle outcome.

Is ABO blood type associated with ovarian stimulation response in patients with diminished ovarian reserve?

PURPOSE: Recent studies have explored the relationship between ABO blood type and serum markers of ovarian reserve, specifically follicle-stimulating hormone (FSH) and anti-mullerian hormone (AMH). The primary objective of this study is to investigate whether there is an association between ABO blood type and ovarian stimulation response in patients with serum markers of diminished ovarian reserve (DOR). METHODS: This is a retrospective study of all patients undergoing controlled ovarian stimulation (COS) for in vitro fertilization (IVF) between May 2010 and July 2013. Patients were sub-grouped, a priori, based on serum AMH levels: ≤1 ng/mL, ≤0.5 ng/mL and ≤0.16 ng/mL. Within each sub-group, demographic, baseline IVF characteristics and COS response parameters based on ABO blood types were compared. The number of mature oocytes retrieved was considered the primary outcome. Analysis of variance (ANOVA) and Chi-square tests were used to compare means and percentages between ABO blood types within groups. RESULTS: Complete data was available for 2575 patients. The mean (± SD) age and BMI of the study cohort was 38.9 (±3.97) years, 23.4 (±5.91) kg/m(2), respectively. The distribution of ABO blood types in the cohort was as follows: 36.8 % (A), 6.56 % (AB), 17.3 % (B), and 39.3 % (O). The demographics and baseline IVF characteristics were comparable among patients with blood types A, AB, B, and O within each AMH group. Within each AMH sub-group, no difference was found in the total days of COS, total gonadotropins administered, peak estradiol level, or number of mature oocytes retrieved based on blood type. CONCLUSIONS: Our results suggest no association between ABO blood type and ovarian stimulation response in patients with DOR. The predictive value of ABO blood type in determining ovarian stimulation response in such patients is currently limited.

Euploid programmed frozen embryo transfer cycles are associated with a higher live birth rate when estradiol levels more closely mimic physiology.

OBJECTIVE: To determine whether peak estradiol (E2) levels above the usual physiologic range (300-500 pg/mL) will impact programmed frozen embryo transfer (FET) outcomes in an ideal study population of those using good-quality single euploid blastocysts. DESIGN: Retrospective cohort study. SETTING: University-based clinic. PATIENTS: Single euploid-programmed FET done at a single academic institution from January 2016 to December 2019. The population was divided into three groups on the basis of peak serum E2 levels during endometrial preparation: group A (E2 <300 pg/mL), group B (300-500 pg/mL), and group C (>500 pg/mL). Group B was used as the reference range for statistical analysis. INTERVENTION: Frozen embryo transfer cycles. MAIN OUTCOME MEASURES: The primary outcome was the live birth rate (LBR). Secondary outcomes included implantation, biochemical, ectopic, and miscarriage rates. RESULTS: A total of 750 FET cycles were included in this study. Poisson regression analysis showed a negative impact of higher peak E2 on the LBR. A decrease in LBR was noted between group C and referent group B (50.2% vs. 63.4%, risk ratio 0.79 [0.68-0.91]) and group A and referent group B (42.5% vs. 63.4%, risk ratio 0.67 [0.46-0.98]). Secondary outcomes were notable for a lower implantation rate when groups A and C were compared with group B and a higher biochemical rate between group C and group B. There was no notable difference between groups in ectopic or miscarriage rates. CONCLUSION: Limiting peak serum E2 levels to 300-500 pg/mL during programmed FET cycles is associated with improved LBRs compared with cycles with peak E2 levels of <300 pg/mL or >500 pg/mL in an ideal study population.

Antimüllerian hormone is not associated with embryo ploidy in patients with and without infertility undergoing in vitro fertilization with preimplantation genetic testing.

OBJECTIVE: To assess the association between antimüllerian hormone (AMH) and embryo ploidy rates in 2 cohorts of patients undergoing in vitro fertilization (IVF) with trophectoderm biopsy for preimplantation genetic testing for aneuploidy (PGT-A): the general population of women pursuing IVF with PGT-A (Infertile cohort) and women pursuing IVF with preimplantation genetic testing for monogenic disorders (PGT-M) owing to the risk of hereditary monogenic diseases (Non-infertile cohort). DESIGN: Retrospective cohort study. SETTING: Academic center. PATIENT(S): Patients undergoing their first cycle of IVF with trophectoderm biopsy and PGT-A or PGT-A and PGT-M in our center between March 2012 and June 2020. Patients of advanced maternal age according to the Bologna criteria (age ≥40 years) and patients who underwent fresh embryo transfers were excluded. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Proportion of euploid, mosaic, and aneuploid embryos per cycle. RESULT(S): "Infertile" (n = 926) and "Non-infertile" (n = 214) patients were stratified on the basis of AMH levels, with low-AMH defined as <1.1 ng/mL in accordance with the Bologna criteria. Age-adjusted regression models showed no relationship between AMH classification and proportion of euploid, mosaic, and aneuploid embryos in the Infertile or Non-infertile cohorts. In the Infertile cohort, no association between AMH classification and embryo ploidy rates was identified in a subgroup analysis of patients aged <35 years, 35-37 years, and 38-39 years. These findings persisted in a sensitivity analysis of infertile patients stratified into AMH (ng/mL) quartile categories. CONCLUSION(S): No association was found between AMH and the proportion of euploid, mosaic, or aneuploid embryos in 2 large cohorts of patients undergoing IVF with PGT-A (Infertile patients) or PGT-A and PGT-M (Non-infertile patients), suggesting that a quantitative depletion of ovarian reserve does not predict the ploidy status of the embryo cohort.

Diagnostic Performance of Ovarian Morphology on Ultrasonography across Anovulatory Conditions-Impact of Body Mass Index.

The study objectives were to determine whether ovarian morphology can distinguish between women with regular menstrual cycles, normo-androgenic anovulation (NA-Anov), and PCOS and whether body mass index (BMI)-specific thresholds improved diagnostic potential. Women with PCOS (biochemical and/or clinical hyperandrogenism and irregular cycles; N = 66), NA-Anov (irregular cycles without clinical and/or biochemical hyperandrogenism; N = 64), or regular cycles (controls; cycles every 21-35 days in the absence of clinical or biochemical hyperandrogenism; N = 51) were evaluated. Participants underwent a reproductive history, physical exam, transvaginal ultrasound, and a fasting blood sample. Linear regression analyses were used to assess the impact of BMI on ovarian morphology across groups. The diagnostic performance of ovarian morphology for anovulatory conditions, and by BMI (lean: <25 kg/m2; overweight: ≥25 kg/m2), was tested using Receiver Operating Characteristic (ROC) curves. Follicle number per ovary (FNPO) and ovarian volume (OV), but not follicle number per cross-section (FNPS), increased across controls, NA-Anov, and PCOS. Overall, FNPO had the best diagnostic performance for PCOS versus controls (AUCROC = 0.815) and NA-Anov and controls (AUCROC = 0.704), and OV to differentiate between PCOS and NA-Anov (AUCROC = 0.698). In lean women, FNPO best differentiated between PCOS and controls (AUCROC = 0.843) and PCOS versus NA-Anov (AUCROC = 0.710). FNPS better distinguished between NA-Anov and controls (AUCROC = 0.687), although diagnostic performance was lower than when thresholds were generated using all participants. In women with overweight and obesity, OV persisted as the best diagnostic feature across all analyses (PCOS versus control, AUCROC = 0.885; PCOS versus NA-Anov, AUCROC = 0.673; NA-Anov versus controls, AUCROC = 0.754). Ovarian morphology holds diagnostic potential to distinguish between NA-Anov and PCOS, with marginal differences in diagnostic potential when participants were stratified by BMI suggesting that follicle number may provide better diagnostic performance in lean women and ovarian size in those with overweight.