Objective To elucidate the role of vitamin D in reproduction by examining the relationship between recipient vitamin D levels and pregnancy rates in donor-recipient IVF cycles. Design Retrospective ...cohort study. Setting Academic tertiary care center. Patient(s) Ninety-nine recipients of egg donation at University of Southern California Fertility. Intervention(s) Serum was collected from egg donor recipients before ET and was tested for vitamin D levels 25(OH)D. Main Outcome Measure(s) Clinical pregnancy as defined by sonographic presence of a heartbeat at 7–8 weeks of gestation. Result(s) In a diverse population of 99 recipients (53% Caucasian, 20% Asian, 16% Hispanic, 7% African American), adjusted clinical pregnancy rates were lower among vitamin D–deficient recipients than among vitamin D–replete recipients (37% vs. 78%). Live-birth rates were 31% among vitamin D–deficient recipients, compared with 59% among vitamin D–replete recipients. There were no differences in adjusted clinical pregnancy and live-birth rates among recipients who were vitamin D deficient 25(OH)D<20 ng/mL vs. among those who were vitamin D insufficient 20 ng/mL ≤ 25(OH)D<30 ng/mL. Conclusion(s) Nonreplete vitamin D status 25(OH)D<30 ng/mL was associated with lower pregnancy rates in recipients of egg donation. Since the oocyte donor-recipient model is able to separate the impact of vitamin D on oocyte vs. endometrium, these data suggest that the effects of vitamin D may be mediated through the endometrium.
Maternal and paternal age at first birth are increasing across the global population. Spontaneous abortion, one of the most common abnormal pregnancy outcomes, is known to occur more frequently with ...increasing maternal age. However, the relationship of advanced paternal age and spontaneous abortion is poorly understood, and previous results have yielded conflicting results.
To examine the influence of paternal age on the risk of spontaneous abortion among singleton pregnancies conceived without assisted reproductive technologies.
This was a retrospective, case-control study using combined pregnancy data from the Centers for Disease Control and Prevention’s 2011–2013 and 2013–2015 National Survey of Family Growth. Spontaneous, singleton pregnancy data from women aged 15–45 years were analyzed. Ongoing pregnancies, induced abortions, ectopic pregnancies, preterm births, and intrauterine fetal deaths were excluded. Bivariate associations of pregnancy outcome (spontaneous abortion at <20 weeks and ≤12 weeks vs. live birth at ≥37 weeks) and paternal age were determined, along with those of maternal age and selected demographic and pregnancy characteristics. Significant associations were included in a multivariable logistic regression, which accounted for multiple pregnancies derived from the same respondent.
A total of 12,710 pregnancies from 6979 women were analyzed, consisting of 2300 (18.2%) spontaneous abortions and 10,410 (81.8%) term live births. Median maternal and paternal ages were 25 and 28 years, respectively. After adjusting for maternal age, race/ethnicity, socioeconomic status, marital status, and pregnancy intention, pregnancies resulting in spontaneous abortions had 2.05 (95% confidence interval, 1.06–2.20) times the odds of being from a father aged 50 years or older, vs. 25–29 years of age. These relationships remained significant when defining SABs at ≤12 weeks (adjusted odds ratio, 2.30; 95% confidence interval, 1.17–4.52).
Paternal age may increase the odds of spontaneous abortion, independent of selected factors, including demographics, pregnancy intention, and maternal age. This association was robust across several gestational age–based definitions of spontaneous abortion, even after adjustment.
The value of preimplantation genetic testing for aneuploidy (PGT-A) as a screening test for in vitro fertilization (IVF) patients has yet to be determined. Several studies demonstrate higher birth ...rates after aneuploidy testing and elective single-embryo transfer (eSET), suggesting the potential for this testing to decrease the risk of multiple gestations, though these studies have important limitations.
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To determine the accuracy of cell-free DNA (cfDNA) in spent embryo medium (SEM) for ploidy and sex detection at the cleavage and blastocyst stages. To determine if assisted hatching (AH) and ...morphologic grade influence cfDNA concentration and accuracy.
Prospective cohort.
Academic fertility center.
Nine patients undergoing IVF; 41 donated two-pronuclei embryos and 20 embryos from patients undergoing preimplantation genetic testing for aneuploidy (PGT-A).
In a donated embryo arm, SEM was collected on days 3 and 5, with one-half of the embryos undergoing AH before and one-half after. In a clinical arm, SEM was collected on day 5 before trophectoderm (TE) biopsy. Samples underwent PGT-A with the use of next-generation sequencing. cfDNA results were compared with corresponding whole embryos and TE biopsies.
Concordance rates, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for ploidy and sex detection with the use of cfDNA.
Of 141 samples, cfDNA was amplified in 39% and 80.4% of days 3 and 5 SEM, respectively. Concordances for ploidy and sex, respectively, were 56.3% and 81.3% between day 3 cfDNA and whole embryos, and 65% and 70% between day 5 cfDNA and TE biopsies. Day 5 cfDNA sensitivity and specificity for aneuploidy were 0.8 and 0.61, respectively. PPV and NPV were 0.47 and 0.88, respectively. Timing of AH and morphology did not influence cfDNA concentration or accuracy.
cfDNA is detectable on days 3 and 5, but more accurate on day 5. Although our data suggest moderate concordance rates, PGT-A with the use of cfDNA must be further optimized before clinical implementation.
Ampliando los límites de detección: la investigación de ADN celular libre en la detección de aneuploidías en embriones
Determinar la precisión del ADN celular libre (ADNcl) en el medio de cultivo utilizado por los embriones (MUE) para la detección de ploidías y el sexo en los estadíos de división celular y blastocisto. Determinar si la eclosión asistida (EA) y el grado de morfología influyen en la concentración y precisión del ADNcl.
Estudio prospectivo.
Centro académico de fertilidad.
Nueve pacientes sometidas a FIV; 41 embriones de dos pronúcleos donados y 20 embriones de pacientes sometidas a la prueba genética preimplantatoria para aneuploidías (PGP-A).
En la rama de los embriones donados, el MUE fue obtenido en los días 3 y 5, en una mitad de los embriones se obtuvo antes de la EA y en la otra mitad después. En la rama clínica, el MUE fue obtenido en el día 5 antes de la biopsia de trofoectodermo (TE). Las muestras fueron sometidas a PGP-A con el uso secuenciación de última generación. Los resultados de ADNcl fueron comparados con su correspondiente embrión completo y con la biopsia de TE.
Tasas de concordancia, sensibilidad, especificidad, valor predictivo positivo (VPP) y valor predictivo negativo (VPN) para la detección de ploidías y el sexo con el uso de ADNcl.
En 141 muestras, el ADNcl fue amplificado en el 39% y 80,4% para los MUE de días 3 y 5, respectivamente. Las concordancias entre ploidías y el sexo fueron del 56,3% y 81,3% para el ADNcl de día 3 y embriones completos respectivamente, y el 65% y 70% para el ADNcl de día 5 y las biopsias de TE. La sensibilidad y especificidad del ADNcl para aneuploidías en día 5 fueron 0,8 y 0,61, respectivamente. El VPP y el VPN fueron 0,47 y 0,88 respectivamente. El tiempo en que se realizó la EA y la morfología no influyeron en la concentración ni en la precisión del ADNcl.
El ADNcl es detectable en los días 3 y 5, pero es más preciso en el día 5. Aunque nuestros datos sugieren tasas moderadas de concordancia, el PGP-A con el uso de ADNcl debe optimizarse aún más antes de su implementación clínica.
Based on American Society for Reproductive Medicine (ASRM) and Society for Assisted Reproductive Technology data available through 2014, ASRM's guidelines for the limits on the number of embryos to ...be transferred in in vitro fertilization (IVF) cycles have been further refined in continuing efforts to promote singleton gestation and reduce the number of multiple pregnancies. This version replaces the document titled Criteria for number of embryos to transfer: a committee opinion that was published most recently in August of 2013 (Fertil Steril 2013;99:44–6).
The purpose of this systematic review is to evaluate if uterine myomas impact the likelihood of pregnancy and pregnancy loss, and if myomectomy influences pregnancy outcomes in asymptomatic women. ...There is insufficient evidence to conclude that the presence of myomas reduces the likelihood of achieving pregnancy. However, there is fair evidence that myomectomy (open or laparoscopic) for cavity-distorting myomas (intramural or intramural with a submucosal component) improves pregnancy rates and reduces the risk of early pregnancy loss. There is fair evidence that hysteroscopic myomectomy for cavity-distorting myomas improves clinical pregnancy rates but insufficient evidence regarding the impact of this procedure on the likelihood of live birth or early pregnancy loss. In women with asymptomatic cavity-distorting myomas, myomectomy may be considered to optimize pregnancy outcomes.
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Accurately predicting the probability of live birth and multiple gestations is important for determining a safe number of embryos to transfer after in vitro fertilization. We developed a model that ...can be fit to individual clinic data for predicting singleton, twin, and total live birth rates after human embryo transfer. The predicted and observed rates of singleton and twin deliveries were compared in a tenfold cross-validation study using data from a single clinic. The model presented accounts for patient age, embryo stage (cleavage or blastocyst), type of transfer cycle (fresh or frozen) and uterine/universal factors. The standardized errors for rates of singleton and twin deliveries were normally distributed and the mean errors were not significantly different from zero (all p > 0.05). The live birth rates per embryo varied from as high as 43% for fresh blastocysts in the 35-year-old age group to as low as 1% for frozen cleavage stage embryos in the 43-year-old age group. This quantitative model or a simplified version can be used for clinics to generate and analyze their own data to guide the number of embryos to transfer to limit the risk of multiple gestations.
Objective To better understand practice patterns and opportunities for standardization of ET. Design Cross-sectional survey. Setting Not applicable. Patient(s) Not applicable. Intervention(s) An ...anonymous 82-question survey was emailed to the medical directors of 286 Society for Assisted Reproductive Technology member IVF practices. A follow-up survey composed of three questions specific to ET technique was emailed to the same medical directors. Descriptive statistics of the results were compiled. Main Outcome Measure(s) The survey assessed policies, protocols, restrictions, and specifics pertinent to the technique of ET. Result(s) There were 117 (41%) responses; 32% practice in academic settings and 68% in private practice. Responders were experienced clinicians, half of whom had performed <10 procedures during training. Ninety-eight percent of practices allowed all practitioners to perform ET; half did not follow a standardized ET technique. Multiple steps in the ET process were identified as “highly conserved;” others demonstrated discordance. ET technique is divided among 1 trial transfer followed immediately with ET (40%); 2 afterload transfer (30%); and 3 direct transfer without prior trial or afterload (27%). Embryos are discharged in the upper (66%) and middle thirds (29%) of the endometrial cavity and not closer than 1–1.5 cm from fundus (87%). Details of each step were reported and allowed the development of a “common” practice ET procedure. Conclusion(s) ET training and practices vary widely. Improved training and standardization based on outcomes data and best practices are warranted. A common practice procedure is suggested for validation by a systematic literature review.
OBJECTIVE:To compare time to ovulation, ovulation rates, and side effect profile of traditional and the stair-step protocol for ovulation induction using clomiphene citrate in women with polycystic ...ovary syndrome (PCOS).
METHODS:We performed a retrospective study of women seeking care for infertility with a diagnosis of PCOS at a university-based infertility clinic from July 2012 to July 2014. We included patients who were resistant to the initial starting dose of 50 mg clomiphene. The primary outcome was time to ovulation. Secondary outcomes included ovulation rates, clinical pregnancy rates, and mild and moderate-to-severe side effects based on dose. For the traditional protocol, higher doses of clomiphene were used each subsequent month if no ovulation occurred. For the stair-step protocol, higher doses of clomiphene were given 7 days after the last dose if no dominant follicles were seen on ultrasonography. Our study had 80% power to detect a 20% difference in ovulation.
RESULTS:One hundred nine patients were included in the analysis with 66 (60.6%) in the traditional and 43 (39.4%) in the stair-step protocol. Age and body mass index were similar between groups. The time to ovulation was decreased in the stair-step protocol group compared with the traditional protocol group (23.1±0.9 days vs 47.5±6.3 days). Ovulation rates were increased in the stair-step group compared with the traditional group at 150 mg (16 37% vs 8 12%, P=.004) and at 200 mg (9 21% vs 3 5%, P=.01). Pregnancy rates were similar between groups once ovulation was achieved (12 18.1% vs 7 16.3%, P=.08). The stair-step protocol had an increased incidence of mild side effects (vasomotor flushes, headaches, gastrointestinal disturbance, mastalgia, changes in mood; 18 41% vs 8 12%), but there was no difference in the incidence of severe side effects (headaches, visual disturbances).
CONCLUSION:For women with PCOS, the stair-step clomiphene protocol is associated with decreased time to ovulation and increased ovulation rates at higher doses when compared with the traditional protocol.
The purpose of this document is to review the current methods of diagnosis and evaluation for men with azoospermia.
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