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.

Embryo ploidy in vitrified versus fresh oocytes: Is there a difference?

PURPOSE: To evaluate embryo ploidy in a cohort of patients who underwent preimplantation genetic testing for aneuploidy (PGT-A) with vitrified oocytes compared to fresh oocytes. METHODS: Patients who underwent their first autologous oocyte vitrification and warming followed by in vitro fertilization (IVF) and trophectoderm biopsy for PGT-A between 1/1/2017 and 12/31/2021 at a single academic institution were included. Patients were compared 1:3 to age-matched controls who underwent their first IVF cycle with fresh oocytes and subsequent trophectoderm biopsy for PGT-A. The primary outcome was the proportions of euploid, mosaic, and aneuploid embryos between those using vitrified versus fresh oocytes. RESULTS: 117 patients who cryopreserved a total of 1,272 mature oocytes were included in the study and were matched with 351 controls using fresh oocytes. The average age was 36.9 ± 2.6 years, and the median interval between oocyte vitrification and warming was 38 months. There were similar numbers of mature oocytes (10.9 ± 4.9 vs. 11.1 ± 6.3, P = .67), fertilized oocytes (7.8 ± 4.0 vs. 8.7 ± 5.5, P = .10), and blastocysts per patient (5.1 ± 3.1 vs. 5.8 ± 4.3, P = .10) between those using vitrified versus fresh oocytes. In terms of embryo ploidy results, there were no statistically significant differences in rates of euploidy (40.1% vs. 41.6%), mosaicism (15.7% vs. 12.0%), or aneuploidy (44.3% vs. 46.4%) (P = .06) between the two groups. CONCLUSIONS: Oocyte vitrification with subsequent warming, fertilization, and trophectoderm biopsy for PGT-A was not associated with adverse chromosomal competence when compared to age-matched controls utilizing fresh oocytes.

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.

Comparison of fresh and frozen ejaculated spermatozoa in sibling oocyte recipient cycles.

RESEARCH QUESTION: Do IVF and intracytoplasmic sperm injection cycles using fresh and frozen ejaculated spermatozoa result in similar pregnancy outcomes in couples with non-male factor infertility? DESIGN: Retrospective cohort study; patients undergoing donor egg recipient cycles, in which oocytes from a single ovarian stimulation were split between two recipients, were reviewed. Two recipients of oocytes from a single donor were paired and categorized based on the type of ejaculated spermatozoa (fresh/frozen). Outcomes included delivery rate, implantation, pregnancy, pregnancy loss and fertilization rates. RESULTS: Of the 408 patients who received oocytes from a split donor oocyte cycle, 45 pairs of patients used discrepant types of ejaculated spermatozoa and were included in the study. Fertilization rate: fresh (74.8%); frozen (68.6%) (P = 0.13). Pregnancy rate: fresh (76%); frozen (67%); delivery rate: fresh (69%); frozen (44%); implantation rate was significantly higher: fresh (64%); frozen (36%) (P = 0.04). Rate of pregnancy loss was significantly higher in the frozen group compared with the fresh group (33% versus 5.9%, P = 0.013). Adjusted odds for delivery was 67% lower in the frozen group (95% CI 0.12, 0.89). Adjusted odds of pregnancy (adjusted OR 0.67, 95% CI 0.20, 2.27) and implantation (adjusted OR 0.5, 95% CI 0.12, 2.12) were not significantly different between the frozen and fresh sperm groups. CONCLUSION: In this model that controls for oocyte quality by using paired recipients from the same donor, frozen ejaculated spermatozoa resulted in lower delivery rates than those using fresh spermatozoa.

Advancing paternal age does not negatively impact fresh embryo transfer cycle outcomes.

RESEARCH QUESTION: What is the impact of advancing paternal age, stratifying for maternal age, on fresh embryo transfer cycle outcomes? DESIGN: All first autologous fresh embryo transfer cycles between 2013 and 2019 at a single high-volume academic institution were retrospectively reviewed. Female age was dichotomized along the cohort median of (37 years) (Female-Young [F-Y]: <37 years; Female-Old [F-O]: ≥37 years). Male age was stratified along the cohort median (38 years) and 90th centile (48 years) (Male-Young [M-Y]: <38 years; Male-Intermediate [M-I]: ≤38 and >48 years; Male-Old [M-O]: ≥48 years). The primary outcome of interest was the odds of live birth using logistic regression. Secondary outcomes included odds of implantation, clinical intrauterine pregnancy and pregnancy loss. All models were adjusted for continuous female age, use of surgically retrieved testicular spermatozoa, severe oligozoospermia and cleavage- versus blastocyst-stage embryo transfer. RESULTS: A total of 6704 couples were included and were divided into six groups based on paternal/maternal age groups (F-Y/M-Y: 2288; F-Y/M-I: 750; F-Y/M-O: 97; F-O/M-Y: 679; F-O/M-I: 2310; F-O/M-O: 580). While some associations were seen on univariable logistic regression, none of the groups with increasing paternal age showed any statistically significant differences on multivariable logistic regression with respect to implantation, clinical intrauterine pregnancy, pregnancy loss or live birth. CONCLUSIONS: Advanced paternal age does not impact clinical outcomes in fresh transfer cycles. The authors postulate that IVF with or without intracytoplasmic sperm injection is able to overcome the deleterious effects of advancing paternal age on sperm quality and subsequent embryo performance.

The use of fresh compared to frozen ejaculated sperm has no impact on fresh embryo transfer cycle reproductive outcomes.

PURPOSE: To compare the reproductive outcomes of fresh embryo transfer (ET) cycles utilizing fresh versus frozen ejaculated sperm. METHODS: First autologous fresh embryo transfer cycles at a single high-volume academic institution between 2013 and 2019 were retrospectively reviewed. IVF cycles using ejaculated sperm were included, and cycles using donor or surgically retrieved sperm were excluded. Sperm concentration was stratified as ≥ 5 and < 5 million/ml. The primary outcome was live birth, and the secondary outcomes were clinical intrauterine pregnancy (IUP) and miscarriage. A multivariable logistic regression model for the aforementioned outcomes was adjusted a priori for sperm concentration as well as maternal and paternal age. RESULTS: A total of 6128 couples were included. Of these, 5780 (94.3%) utilized fresh sperm, and 348 (5.7%) frozen sperm. A total of 5716 (93.2%) had sperm concentrations ≥ 5 million/ml and 412 (6.7%) had sperm concentrations < 5 million/ml. On multivariable logistic regression, the use of freshly ejaculated sperm was not associated with significantly different odds of clinical IUP, miscarriage, or live birth when compared to cycles using frozen sperm. CONCLUSION: For couples conceiving via fresh ET, the use of fresh versus frozen ejaculated sperm is not associated with reproductive outcomes.

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.

Medical and mental health implications of gestational surrogacy.

Gestational surrogacy in the United States has quadrupled since 1999, but to date, only a few states explicitly permit compensated gestational surrogacy. Current legal prohibitions are often influenced by outdated and stereotyped understandings of surrogacy. It is increasingly important to understand the current literature about the medical and mental health impacts of surrogacy and how state legislatures have addressed compensated gestational surrogacy in recent years. Based on this review, we found no evidence of substantial adverse medical or psychological outcomes among women who are gestational carriers or among the children they give birth to. The literature suggests that gestational surrogacy is a safe and increasingly popular option for families as long as rigorous screening and medical, psychological, and social supports are equitably provided. As states move to responsibly legalize and regulate gestational surrogacy, there is a continued need for further longitudinal studies on the health and psychological outcomes of gestational surrogacy.

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.

One thousand seventy-eight autologous IVF cycles in women 45 years and older: the largest single-center cohort to date.

PURPOSE: The purpose of this study was to determine IVF outcomes in women 45 years and older using autologous oocytes. METHODS: This is a retrospective cohort study reviewing all IVF cycles in women ≥ 45 years old from January 1995 to June 2015 that were conducted at one academic medical center. One thousand seventy-eight fresh, autologous IVF cycles met inclusion criteria. PGD/S, natural IVF, and donor egg cycles were excluded. Outcomes were analyzed for the different age groups (age 45, n = 773; age 46, n = 221; age 47, n = 57; age 48, n = 22; age 49, n = 5). Primary outcome measures included IVF cycle characteristics, total pregnancy loss, clinical pregnancy, and live birth rates, and were stratified according to patient age. RESULTS: Mean age of patients in the study cohort was 45.4 ± 0.72. 11.7% of patients did not start due to an elevated FSH or cyst and 28.5% of patients were canceled prior to oocyte retrieval. The overall pregnancy rate per transfer was 18.7% (117/626), of which 82.1% ended in a pregnancy loss. The overall clinical pregnancy and live birth rates per transfer were 9.6 and 3.4%, respectively, which did not differ between age groups. Per cycle start women aged 45 had significantly higher positive pregnancy rates compared to women aged 46 and 47 (14.1 vs. 8.6 vs. 5.9%, p = 0.04). For women 45 years old, the live birth rate was 2.9% per cycle start and was 4.4% per embryo transfer. Of the 21 live births, 20 were in women aged 45 and one live birth was in a 46-year-old woman. There were no live births in any patient with ≤ 4 oocytes retrieved. CONCLUSION: Autologous IVF in women aged 45 with acceptable ovarian reserve is not futile; however, it does carry very low prognosis. Patients aged 46 and older should be counseled appropriately that a live birth seems highly unlikely.

IL-1ß predicts IVF outcome: a prospective study.

PURPOSE: Retrospective cohort studies have shown a relationship between maternal serum interleukin-1ß (IL-1ß) and interleukin-1 receptor antagonist (IL-1Ra) levels and in vitro fertilization (IVF) cycle outcome. The objective of this investigation was to explore the correlation between serum IL-1ß and/or IL-1Ra levels obtained prospectively and IVF outcomes. METHODS: Sera from 205 women were collected just prior to initiation of their IVF cycle, at the time of human chorionic gonadotropin administration, day 24 of IVF cycle, day 28, and day 35. Sera were analyzed for IL-1ß and IL-1Ra using commercially available ELISA kits. Cycle outcomes were followed prospectively. Data were analyzed using Friedman analysis of variance by ranks and chi-square analysis. RESULTS: Among women with a viable pregnancy, IL-1ß serum levels increased over time for those that proceeded to deliver or had an ongoing pregnancy. There was no increase in serum levels for those with subsequent pregnancy loss. Of the women that had an embryo transfer, detectable IL-1ß levels at the start of the cycle were associated with successful IVF outcome (p = 0.027). Of women with a positive pregnancy test, undetectable IL-1ß at the start of the cycle were associated with subsequent pregnancy loss (p = 0.046). For all IL1-Ra serum analysis, there were no significant results. CONCLUSIONS: The increasing levels of IL-1ß over time are consistent with the known role of the IL-1 cytokine family in implantation and pregnancy. Additionally, we confirm in a prospective investigation the positive relationship between detectable serum IL-1ß at the start of IVF cycle and outcome.

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.