Perinatal outcomes are similar in programmed and modified natural frozen embryo transfer cycles.

RESEARCH QUESTION: How do perinatal outcomes differ between programmed and modified natural frozen embryo transfer (FET) cycles? DESIGN: A retrospective cohort study of 839 patients was undertaken at a university-affiliated fertility practice undergoing single blastocyst FET cycles between 2014 and 2020. The primary outcome measures were the incidence of ischaemic placental disease, small for gestational age (SGA), intrauterine growth restriction (IUGR), preterm delivery, birth weight, and mode of delivery. RESULTS: When comparing programmed FET cycles with modified natural FET cycles, there was no increased risk of ischaemic placental disease [adjusted risk ratio (aRR) 0.83, 95% CI 0.61-1.14], IUGR (unadjusted RR 0.50, 95% CI 0.14-1.77), preterm delivery (aRR 1.11, 95% CI 0.72-1.70) or SGA (aRR 0.69, 95% CI 0.40-1.19). Patients in the programmed cohort had increased risk of caesarean delivery (aRR 1.32, 95% CI 1.10-1.59). These outcomes were unchanged when limited to patients undergoing their first FET cycle. CONCLUSIONS: There are no differences in patient and neonatal clinical outcomes between programmed and modified natural FET cycles. The choice of FET protocol should remain a shared decision between patient and provider.

Endometrial compaction does not predict live birth in single euploid frozen embryo transfers: a prospective study.

STUDY QUESTION: Is there a relationship between endometrial compaction and live birth in euploid frozen embryo transfer (FET) cycles? SUMMARY ANSWER: Live birth rates (LBRs) were similar in both patients that demonstrated endometrial compaction or no compaction in single euploid FETs. WHAT IS KNOWN ALREADY: There has been increasing interest in the correlation between endometrial compaction and clinical outcomes but there has been conflicting evidence from prior investigations. STUDY DESIGN, SIZE, DURATION: This was a prospective observational study from 1 September 2020 to 9 April 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study was performed at a single, academically affiliated fertility center in which patients who had an autologous single euploid FET using a programmed or modified natural cycle protocol were included. All embryos had trophectoderm biopsy for preimplantation genetic testing for aneuploidy followed by vitrification at the blastocyst stage. Two ultrasound measurements of endometrial thickness (EMT) were obtained. The first measurement (T1) was measured transvaginally within 1 day of initiation of progesterone or ovulation trigger injection, and a second EMT (T2) was measured transabdominally at the time of embryo transfer (ET). The primary outcome (LBR) was based on the presence and proportion of compaction (percentage difference in EMT between T1 and T2). MAIN RESULTS AND THE ROLE OF CHANCE: Of the 186 participants included, 54%, 45%, 35%, 28% and 21% of women exhibited >0%, ≥5%, ≥10%, ≥15% and ≥20% endometrial compaction, respectively. Endometrial compaction was not predictive of live birth at any of the defined cutoffs. A sub-analysis stratified by FET protocol type (n = 89 programmed; n = 97 modified natural) showed similar results. LIMITATIONS, REASONS FOR CAUTION: There was the potential for measurement error in the recorded EMTs. The T2 measurement was performed transabdominally, which may cause potential measurement error, as it is generally accepted that transvaginal measurements of EMT are more accurate, though, any bias is expected to be non-differential. The sub-analysis performed looking at FET protocol type was underpowered and should be interpreted with caution. Our study, however, represents a pragmatic approach, as it allowed patients to avoid having to come in for an extra transvaginal ultrasound the day before or on the day of ET. WIDER IMPLICATIONS OF THE FINDINGS: Assessing endometrial compaction may lead to unnecessary cycle cancellation. However, further studies are needed to determine if routine screening for endometrial compaction would improve clinical outcomes. STUDY FUNDING/COMPETING INTEREST(S): No authors report conflicts of interest or disclosures. There was no study funding. TRIAL REGISTRATION NUMBER: NCT04330066.

Multifoetal gestations mediate the effect of in vitro fertilisation (IVF) on ischaemic placental disease in autologous oocyte IVF more than donor oocyte IVF.

BACKGROUND: Ischaemic placental disease (IPD) affects 16%-23% of pregnancies in the United States. In vitro fertilisation (IVF) is a risk factor for IPD, and the magnitude of increase in risk differs for individuals using donor oocytes (donor IVF) versus their own oocytes (autologous IVF). In addition, multifoetal gestations, which are more common in IVF than non-IVF pregnancies, also are a risk factor for IPD. OBJECTIVE: To quantify the contribution of multifoetal gestations to the association between IVF and IPD. METHODS: We conducted a retrospective cohort study at a tertiary hospital from 1 January, 2000 to 1 August 2018 using electronic medical records and state vital statistics data. IPD was defined as preeclampsia, placental abruption, small for gestational age (SGA) birth or an intrauterine foetal demise due to placental insufficiency. We used mediation analysis to decompose the total effect of IVF on IPD into a natural direct effect and an indirect effect through multifoetal gestations. We repeated the analyses separately for donor and autologous IVF. All models were adjusted for maternal age, race, parity, insurance, year of delivery and account for multiple pregnancies per person. RESULTS: We identified 86,514 deliveries, of which 281 resulted from donor IVF and 4173 resulted from autologous IVF. IVF pregnancies had 1.99 (95% CI 1.88, 2.10) times the risk of IPD compared to non-IVF pregnancies, and 75.5% of this increased risk was mediated by multifoetal gestations. Autologous IVF pregnancies had 1.95 (95% CI 1.84, 2.07) times the risk of IPD compared to non-IVF pregnancies, and the per cent mediated was 78.8%. Donor IVF pregnancies had 2.50 (95% CI 2.09, 2.92) times the risk of IPD, but the per cent mediated was 37.5%. CONCLUSION: The majority of the association between autologous IVF and IPD was mediated through multifoetal gestations; however, this was not the case for donor IVF pregnancies.

Clinical outcomes and utilization from over a decade of planned oocyte cryopreservation.

RESEARCH QUESTION: What is the clinical experience of patients who have undergone planned oocyte cryopreservation and oocyte thawing and warming? DESIGN: Retrospective observational cohort study. All women who completed planned oocyte cryopreservation at a single large university-affiliated fertility centre between June 2006 and October 2020 were identified, including the subset who returned to use their oocytes. Patients who underwent oocyte cryopreservation for medical reasons were excluded. Baseline demographics, oocyte cryopreservation and thawing-warming cycle parameters, and clinical outcomes, were extracted from the electronic medical record. The primary outcome was cumulative live birth rate (LBR), and secondary outcomes were cumulative clinical pregnancy rate (CPR), and CPR and LBR per transfer. Results were stratified by age at time of cryopreservation (<38 and ≥38 years). RESULTS: Of 921 patients who underwent planned oocyte cryopreservation, 68 (7.4%) returned to use their oocytes. Forty-six patients (67.6%) completed at least one embryo transfer. The CPR per transfer was 47.5% and LBR was 39.3%. The cumulative LBR per patient who initiated thawing-warming was 32.4%. Cycle outcomes were not significantly different in patients aged younger than 38 years and those aged 38 years or over. No patient aged 40 years or older (n = 6) was successful with their cryopreserved oocytes. Ten patients (14.7%) who were unsuccessful with their cryopreserved oocytes achieved a live birth using donor oocytes, with most (7/10) of these patients aged 38 years and older. CONCLUSION: Only a small percentage of patients returned to use their oocytes, and 32% of those were able to achieve a live birth.

Low cryoprotectant concentration rapid vitrification of mouse oocytes and embryos.

Vitrification of mammalian oocytes and embryos is typically a two-step procedure involving two solutions of increasing concentrations of cryoprotectants. In the present study, we report a simple vitrification protocol that uses low cryoprotectant concentration and a single medium (LCSM). This medium, along with the traditional high concentration two media (HCTM) protocol, was used to vitrify mouse oocytes, zygotes, and blastocysts using silica capillary, cryotop, cryolock, and 0.25 ml straws. Survival rates, two-cell rates, and blastocyst formation rates were compared for oocytes and zygotes vitrified using both protocols. Results show that the LCSM protocol was as good as or better than the traditional HCTM protocol for vitrifying mouse MII oocytes and zygotes using silica capillary, cryotop, and cryolock. On the other hand, for blastocysts, only silica capillary using LCSM had comparable results with the traditional HCTM protocol while cryolock and cryotop had significantly lower percentages of re-expanded and hatched blastocysts. Collapsing blastocysts prior to vitrification or longer duration for better cryoprotectant distribution in multicellular embryos may improve the outcome. In conclusion, the LCSM protocol, with one medium of much lower cryoprotectant concentrations and shorter equilibration time, reduces exposure to cryoprotectant toxicity while improves efficiency, consistency and reliability for mammalian oocyte and embryo preservation.

Placenta Accreta Spectrum: In Vitro Fertilization and Non-In Vitro Fertilization and Placenta Accreta Spectrum in a Massachusetts Cohort.

OBJECTIVE: The incidence of placenta accreta spectrum (PAS) has been increasing in the United States. In addition, there has also been an increase in the utilization of in vitro fertilization (IVF). The IVF pregnancies confer an increased risk of adverse obstetric and neonatal outcomes, but there is limited data on whether IVF is associated with PAS. The aim of this study is to assess the association between IVF and the risk of PAS. STUDY DESIGN: This was a retrospective cohort study of deliveries from January 1, 2013 to August 1, 2018 at a tertiary hospital in the Massachusetts. IVF pregnancies were compared with non-IVF pregnancies, and PAS diagnosis was confirmed by histopathology reports. Hospital administrative data and medical record review were used, and supplemented with data from birth certificates from the Massachusetts Department of Public Health. RESULTS: We identified 28,344 pregnancies that met inclusion criteria, of which 1,418 (5.0%) were IVF pregnancies. The overall incidence of PAS was 0.4% (2.2% in the IVF group and 0.3% in the non-IVF group). Women who underwent IVF had 5.5 times the risk of PAS (95% confidence interval [CI]: 3.4-8.7) compared with women in the non-IVF group, adjusted for maternal age, nulliparity, and year of delivery (Table 5). Compared with women in the non-IVF group, the IVF group had fewer prior cesarean deliveries (22.6 vs. 64.2%) and a lower prevalence of placenta previa (19.4 vs. 44.4%). CONCLUSION: Women with an IVF pregnancy carry an increased risk of PAS compared with non-IVF. Among women who underwent IVF, there was a lower prevalence of prior cesarean deliveries and placenta previa. Future work is needed to identify the mechanism of association for this increased risk as well as a reliable tool for antenatal detection in this cohort of women. KEY POINTS: · IVF pregnancies have higher risk of PAS than non-IVF pregnancies.. · IVF pregnancies with PAS do not exhibit common risk factors.. · IVF may be an independent risk factor for PAS..

The importance of mediation in reproductive health studies.

A mediator is a factor that occurs after the exposure of interest, precedes the outcome of interest (i.e. between the exposure and the outcome) and is associated with both the exposure and the outcome of interest (i.e. is on the pathway between exposure and outcome). Mediation analyses can be valuable in many reproductive health contexts, as mediation analysis can help researchers to better identify, quantify and understand the underlying pathways of the association they are studying. The purpose of this commentary is to introduce the concept of mediation and provide examples that solidify understanding of mediation for valid discovery and interpretation in the field of reproductive medicine.

Infertility remains a top stressor despite the COVID-19 pandemic.

RESEARCH QUESTION: What is the psychological impact of the COVID-19 pandemic on infertility patients? DESIGN: An anonymous cross-sectional online survey was sent to patients who attended a large university-affiliated infertility practice in the USA between 1 January 2019 and 1 April 2020. At three different time-points respondents were asked to note their top three stressors, from a list of 10 commonly reported life stressors. RESULTS: The questionnaire was sent to 10,481 patients, with 3604 responses (response rate 34%) received. A total of 2202 non-pregnant female respondents were included in the final analysis. One-third of respondents had a prior diagnosis of an anxiety disorder, and 11% reported taking anxiolytic medications; over one-quarter had a prior diagnosis of a depressive disorder and 11% reported taking antidepressant medications. At all three time-points, infertility was noted to be the most frequent top stressor. Coronavirus was noted to be the third most common stressor among the respondents in early March but, at the time of writing, is similar to that of infertility (63% and 66%, respectively). A total of 6% of patients stated that infertility treatment, including IVF, should not be offered during the COVID-19 pandemic. CONCLUSION: Despite the unprecedented global pandemic of COVID-19, causing economic and societal uncertainty, the stress of infertility remains significant and is comparable a stressor to the pandemic itself.

In vitro culture of ovarian follicles from Peromyscus.

The ovarian follicle is the fundamental functional tissue unit of mammalian ovary. Each ovarian follicle contains one single oocyte. Isolation and in vitro culture of ovarian follicles to obtain fertilizable oocytes have been regarded as a promising strategy for women to combat infertility. The follicles from Peromyscus are considered as a better model than that from inbred mice for studying follicle culture. This is because Peromyscus mice are outbred (as with humans) with an increased life span. In this article, we reviewed studies on this subject conducted using Peromyscus follicles. These studies show that the conventional 2D micro-drop and 3D hanging-drop approaches established for in vitro culture of early preantral follicles from inbred mice are not directly applicable for cultivating the follicles from Peromyscus. However, the efficiency could be significantly improved by culturing multiple early preantral follicles in one hanging drop of Peromyscus ovarian cell-conditioned medium. It is further revealed that the mechanical heterogeneity in the extracellular matrix of ovary is crucial for developing early preantral follicles to the antral stage and for the subsequent ovulation to release cumulus-oocyte complex. These findings may provide valuable guidance for furthering the technology of in vitro follicle culture to restore fertility in the clinic.

To test or not to test? A framework for counselling patients on preimplantation genetic testing for aneuploidy (PGT-A).

STUDY QUESTION: What is the treatment path and cumulative live birth (CLB) rate from a single oocyte retrieval of patients who intend to pursue PGT-A at the start of an IVF cycle compared to matched controls? SUMMARY ANSWER: The choice of PGT-A at the start of the first IVF cycle decreases the CLB per oocyte retrieval for patients <38 years of age, however patients ≥38 years of age benefit significantly per embryo transfer (ET) when live birth (LB) is evaluated. WHAT IS KNOWN ALREADY: PGT-A has been shown to reduce the practice of transferring multiple embryos and to confer a higher live birth rate per transfer. STUDY DESIGN, SIZE, DURATION: This is a retrospective cohort study from December 2014 to September 2016, involving 600 patients: those intending PGT-A for their first IVF cycle (N = 300) and their matched controls. Post-hoc power calculations (alpha of 0.05, power of 0.80) indicated that our study was powered adequately to demonstrate significant differences in CLB per retrieval and LB per transfer. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was performed at a large academically affiliated infertility practice where approximately 80% of patients have insurance coverage for fertility care. Patients were identified through electronic medical records, and those who intended to pursue PGT-A at the start of stimulation were assessed. Patients were matched by age, time of oocyte retrieval and oocyte yield to the same number of controls. CLB outcomes per single retrieval, including the fresh and frozen transfers arising from the initial stimulation cycle, were calculated. MAIN RESULTS AND THE ROLE OF CHANCE: PGT-A was not beneficial when CLB rate was assessed per retrieval, however its benefits were significant when LB rate was assessed per transfer. First cycle, <38 year-old patients who intended to have PGT-A had a significantly (P < 0.001) lower CLB rate per oocyte retrieval compared to controls (49.4% vs. 69.1%). Conversely, patients ≥ 38 years in the PGT-A group had similar CLB rates compared to controls per oocyte retrieval, while LB rates per transfer were doubled compared to controls (62.1% vs. 31.7%; P < 0.001). Of the first-cycle PGT-A and control patients, 25.3% and 2.3% failed to achieve a transfer, respectively. LIMITATIONS, REASONS FOR CAUTION: This is not a true intention-to-treat study, due to its retrospective nature. Additionally, the number of patients with two or more previous miscarriages was significantly greater in the PGT-A group as compared to controls, however a sub-analysis showed that this failed to impact outcomes. WIDER IMPLICATIONS OF THE FINDINGS: The findings indicate that PGT-A may be detrimental for those <38 years old undergoing their first IVF cycle. PGT-A has the greatest clinical impact when a transfer is achieved in the ≥38 years old population. This study evaluates the typical treatment path following a patient's choice to pursue PGT-A at the cycle start, and can be used as a guide for counselling patients in relation to age and cycle number. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

Pre-pregnancy caffeine and caffeinated beverage intake and risk of spontaneous abortion.

PURPOSE: To investigate the relation between pre-pregnancy caffeine and caffeinated beverage intake and risk of spontaneous abortion (SAB). METHODS: Our prospective cohort study included 15,590 pregnancies from 11,072 women with no history of SAB in the Nurses' Health Study II (1991-2009). Beverage intake was assessed every 4 years using a validated questionnaire. Pregnancies were self-reported with case pregnancies lost spontaneously at <20 weeks gestation. Multivariable log-binomial regression models with generalized estimating equations were used to estimate the relative risks (RRs) and 95 % confidence intervals (CIs). RESULTS: There was a positive linear trend across categories of pre-pregnancy caffeine intake and risk of SAB such that women consuming >400 mg/day had 1.11 (95 % CI 0.98, 1.25) times the risk of SAB compared to women consuming <50 mg/day (p trend = 0.05). Total coffee intake had a positive, linear association with SAB. Compared to women with no pre-pregnancy coffee intake, women consuming ≥4 servings/day had a 20 % (6, 36 %) increased risk of SAB (p trend = 0.01). There was no difference in the association between caffeinated and decaffeinated coffee and risk of SAB. Pre-pregnancy intake of caffeinated tea, caffeinated soda, and decaffeinated soda had no association with SAB. CONCLUSIONS: Pre-pregnancy coffee consumption at levels ≥4 servings/day is associated with increased risk of SAB, particularly at weeks 8-19.

Cryopreservation of human spermatozoa with minimal non-permeable cryoprotectant.

Cryopreservation of human spermatozoa is a commonly used technique in assisted reproduction, however freezing low concentrations of sperm while maintaining adequate post-thaw motility remains a challenge. In an effort to optimize post-thaw motility yields, low volumes of human sperm were frozen in polyimide-coated fused silica micro-capillaries using 0.065 M, 0.125 M, 0.25 M, or 0.5 M trehalose as the only cryoprotectant. Micro-capillaries were either initially incubated in liquid nitrogen vapor before plunging into liquid nitrogen, or directly plunged into liquid nitrogen. Post thaw sperm counts and motility were estimated. Spermatozoa that were initially incubated in liquid nitrogen vapor had greater post thaw motility than those plunged immediately into liquid nitrogen independent of trehalose concentration. The protective effect of 0.125 M d-glucose, 3-O-methyl-d-glucopyranose, trehalose, sucrose, raffinose, or stachyose were evaluated individually. Trehalose and sucrose were the most effective cryoprotectants, recovering 69.0% and 68.9% of initial sperm motility, respectively.

Prepregnancy Low to Moderate Alcohol Intake Is Not Associated with Risk of Spontaneous Abortion or Stillbirth.

BACKGROUND: Numerous studies have documented the negative effects of maternal alcohol consumption during pregnancy on risk of pregnancy loss, yet whether prepregnancy alcohol intake affects the risk of spontaneous abortion is still unclear. OBJECTIVE: This study aimed to assess prepregnancy alcohol intake and risk of spontaneous abortion and stillbirth. METHODS: Our prospective cohort study included 27,580 pregnancies reported by 17,929 women in the Nurses' Health Study II between 1990 and 2009. Alcohol intake was assessed in 1989 and 1991 and every 4 y thereafter with the use of a validated questionnaire. Women were classified into 5 categories of consumption: 0, 0.1-1.9, 2-4.9, 5-9.9, and ≥10 g/d (1 serving = ∼12 g). Pregnancies were self-reported, with case pregnancies lost spontaneously (spontaneous abortion after gestation of <20 wk and stillbirth after gestation of ≥20 wk) and comparison pregnancies not ending in fetal loss (live birth, ectopic pregnancy, or induced abortion). Multivariable log-binomial regression models with generalized estimating equations were used to estimate RRs and 95% CIs. RESULTS: Incident spontaneous abortion and stillbirth were reported in 4326 (15.7%) and 205 (0.7%) pregnancies, respectively. Prepregnancy alcohol intake was not associated with spontaneous abortion. Compared with women who did not consume alcohol, the multivariable RRs (95% CIs) for increasing categories of alcohol intake among women who did consume alcohol were 1.04 (0.97, 1.12) for 0.1-1.9 g/d, 1.02 (0.94, 1.11) for 2-4.9 g/d, 1.01 (0.92, 1.10) for 5-9.9 g/d, and 0.98 (0.88, 1.09) for ≥10 g/d (P-trend = 0.45). Women who consumed ≥2 servings beer/wk before pregnancy had a 9% (95% CI: 1%, 17%) lower risk of spontaneous abortion than did women who consumed <1 serving beer/mo; however, this association did not persist in various sensitivity analyses. Prepregnancy consumption of wine and liquor were not associated with spontaneous abortion. Total alcohol and specific alcohol beverage intake before pregnancy were not associated with stillbirth. CONCLUSION: Prepregnancy alcohol intake was not related to risk of incident spontaneous abortion or stillbirth in women with no history of pregnancy loss. Our results provide reassuring evidence that low to moderate alcohol intake (≤12 g/d) before pregnancy initiation does not affect risk of pregnancy loss.

Processed meat intake is unfavorably and fish intake favorably associated with semen quality indicators among men attending a fertility clinic.

Emerging literature suggests that men's diets may affect spermatogenesis as reflected in semen quality indicators, but literature on the relation between meat intake and semen quality is limited. Our objective was to prospectively examine the relation between meat intake and indicators of semen quality. Men in subfertile couples presenting for evaluation at the Massachusetts General Hospital Fertility Center were invited to participate in an ongoing study of environmental factors and fertility. A total of 155 men completed a validated food-frequency questionnaire and subsequently provided 338 semen samples over an 18-mo period from 2007-2012. We used linear mixed regression models to examine the relation between meat intake and semen quality indicators (total sperm count, sperm concentration, progressive motility, morphology, and semen volume) while adjusting for potential confounders and accounting for within-person variability across repeat semen samples. Among the 155 men (median age: 36.1 y; 83% white, non-Hispanic), processed meat intake was inversely related to sperm morphology. Men in the highest quartile of processed meat intake had, on average, 1.7 percentage units (95% CI: -3.3, -0.04) fewer morphologically normal sperm than men in the lowest quartile of intake (P-trend = 0.02). Fish intake was related to higher sperm count and percentage of morphologically normal sperm. The adjusted mean total sperm count increased from 102 million (95% CI: 80, 131) in the lowest quartile to 168 million (95% CI: 136, 207) sperm in the highest quartile of fish intake (P-trend = 0.005). Similarly, the adjusted mean percentages of morphologically normal sperm for men in increasing quartiles of fish intake were 5.9 (95% CI: 5.0, 6.8), 5.3 (95% CI: 4.4, 6.3), 6.3 (95% CI: 5.2, 7.4), and 7.5 (95% CI: 6.5, 8.5) (P-trend = 0.01). Consuming fish may have a positive impact on sperm counts and morphology, particularly when consumed instead of processed red meats.

The impact of supraphysiologic serum estradiol levels on peri-implantation embryo development and early pregnancy outcome following in vitro fertilization cycles.

PURPOSE: To determine the impact of elevated serum estradiol levels (EE2-defined as levels > 90th percentile) on the day of hCG administration during IVF on oocyte fertilization, embryo development, implantation, clinical pregnancy and miscarriage rates. METHODS: A total of 2,995 consecutive IVF cycles in 1,889 patients with non-donor oocyte retrieval resulting in fresh embryo transfer between 1/1/2005 and 12/31/2011 were analyzed. Cycles were stratified by serum E2 level on the day of hCG administration into those with levels >90th percentile and ≤ 90th percentile. Rates of normal fertilization, embryo development, positive pregnancy test, implantation, clinical pregnancy and spontaneous miscarriage were compared. RESULTS: Serum estradiol above the 90th percentile on the day of hCG administration was associated with a significantly lower rate of normal fertilization (68.6 ± 20 vs. 71.6 ± 21, p = 0.02) when compared with patients with a lower serum estradiol threshold. The proportion of embryos that progressed from 2PN to 6-8 cell on day 3 was not different between the two groups. Although rates of positive pregnancy test (55.2 % vs. 57 %), implantation (26.4 % vs. 28.5 %) and clinical pregnancy (45.5 % vs. 49.4 %) were lower in patients with a higher estradiol threshold, these differences were not statistically significant. Similarly, there was no difference in the spontaneous miscarriage rates between the two groups (8.4 % vs. 7.1 %). CONCLUSIONS: Serum estradiol levels above the 90th percentile on the day of hCG administration is associated with lower oocyte fertilization rate; however, such levels do not impact embryo development, implantation, clinical pregnancy or spontaneous miscarriage rates.

Assisted reproduction and risk of depressive relapse: considerations for treatment.

BACKGROUND: At present, there is a lack of systematic data regarding the risk of relapse of psychiatric disorders in women undergoing infertility treatment. Clinicians would benefit from a systematic study of the biological sequelae of stress and the clinical implications for women with histories of depression or anxiety disorders undergoing treatment for infertility. Women with histories of major depressive disorder may be vulnerable to the stress involved in the process of assisted reproduction, and treatment changes during this time in anticipation of a pregnancy may affect relapse rates. METHODS: We have highlighted the elements important to the care of women undergoing assisted reproduction with histories of depression in the following case report and review of the relevant literature. RESULTS: No clinical guidelines currently exist for prevention of depressive relapse in women seeking infertility treatment. Due to concerns about medication exposure during a potential pregnancy, many women will avoid antidepressants. CONCLUSIONS: The profession needs to identify women at risk of depressive relapse and create evidence-based treatment guidelines for their management. Similarly, among patients who may be pregnant, providers should monitor mood, psychotherapeutic approaches, and collaborative decision-making about medication use carefully.

Modified natural and optimized programmed frozen embryo transfers have equivalent live birth rates: an analysis of 6,682 cycles.

OBJECTIVE: To compare the live birth rates (LBRs) in modified natural and programmed single blastocyst frozen embryo transfer (FET) cycles. DESIGN: Retrospective cohort study. SETTING: University-affiliated fertility practice. PATIENT(S): Patients who underwent single blastocyst FETs between January 2014 and December 2019. A total of 15,034 FET cycles from 9,092 patients were reviewed; 1,186 modified natural and 5,496 programmed FET cycles from 4,532 patients met the inclusion criteria for analysis. INTERVENTION(S): No intervention. MAIN OUTCOME MEASURE(S): The primary outcome measure was the LBR. RESULT(S): There was no difference in live birth after programmed cycles using intramuscular (IM) progesterone or a combination of vaginal progesterone and IM progesterone compared with that after modified natural cycles (adjusted relative risks, 0.94 [95% confidence interval {CI}, 0.85-1.04] and 0.91 [95% CI, 0.82-1.02], respectively). The relative risk of live birth decreased in programmed cycles that used exclusively vaginal progesterone compared with that in modified natural cycles (adjusted relative risk, 0.77 [95% CI, 0.69-0.86]). CONCLUSION(S): The LBR decreased in programmed cycles that used only vaginal progesterone. However, no difference in the LBRs existed between modified natural and programmed cycles if programmed cycles used either IM progesterone or a combination of IM and vaginal progesterone protocols. This study demonstrates that modified natural FET cycles and optimized programmed FET cycles have equivalent LBRs.

Simulation-based training for embryo transfer for clinicians with differing levels of expertise: an application of the American Society for Reproductive Medicine Embryo Transfer Simulator.

Objective: To compare the learning curve of clinicians with different levels of embryo transfer (ET) experience using the American Society for Reproductive Medicine (ASRM) Embryo Transfer Simulator. Design: Prospective cohort study. Setting: Single large university-affiliated in vitro fertilization center. Patients: Participants with 3 levels of expertise with ET were recruited: "group 1" (Reproductive Endocrinology and Infertility attendings), "group 2" (Reproductive Endocrinology and Infertility nurses, advance practice providers, or medical assistants), and "group 3" (Obstetrics and Gynecology resident physicians). Interventions: All participants completed ET simulation training using uterine cases A, B, and C (easiest to most difficult) of the ASRM ET Simulator. Participants completed each case 5 times for a total of 15 repetitions. Main Outcome Measures: The primary outcome was ET simulation scores analyzed at each attempt for each uterine case, with a maximum score of 155. Secondary outcomes included self-assessed comfort levels before and after the completion of the simulation and total duration of ET. Comfort was assessed using a 5-point Likert scale. Results: Twenty-seven participants with 3 different levels of expertise with ET were recruited from December 2020 to February 2021. For cases A and B, median total scores were not significantly different between groups 1 and 3 at first or last attempts. Group 2 did not perform as well as group 3 at the beginning of case A or group 1 at the end of case B. All groups demonstrated a decrease in total time from the first attempt to the last attempt for both cases. For case C, the "difficult" uterus, groups 2 and 3 exhibited the greatest improvement in total median score: from 0 to 75 from the first to last attempt. Group 1 scored equally well from first through last attempts. Although no one from group 2 or 3 achieved a passing score with the first attempt (80% of the max score), approximately 30% had passing scores at the last attempt. Groups 1 and 3 showed a significant decrease in total time across attempts for case C. Following simulation, 100% of groups 2 and 3 reported perceived improvement in their skills. Group 3 showed significant improvement in comfort scores with Likert scores of 1.71 ± 0.76 and 1.0 ± 0.0 for the "Easy" and "Difficult" cases, respectively, before simulation and 4.57 ± 0.53 and 2.4 ± 1.1 after simulation. Conclusions: The ASRM ET Simulator was effective in improving both technical skill and comfort level, particularly for those with little to no ET experience and was most marked when training on a difficult clinical case.

Dietary fat and semen quality among men attending a fertility clinic.

BACKGROUND: The objective of this study was to examine the relation between dietary fats and semen quality parameters. METHODS: Data from 99 men with complete dietary and semen quality data were analyzed. Fatty acid levels in sperm and seminal plasma were measured using gas chromatography in a subgroup of men (n = 23). Linear regression was used to determine associations while adjusting for potential confounders. RESULTS: Men were primarily Caucasian (89%) with a mean (SD) age of 36.4 (5.3) years; 71% were overweight or obese; and 67% were never smokers. Higher total fat intake was negatively related to total sperm count and concentration. Men in the highest third of total fat intake had 43% (95% confidence interval (CI): 62-14%) lower total sperm count and 38% (95% CI: 58-10%) lower sperm concentration than men in the lowest third (P(trend) = 0.01). This association was driven by intake of saturated fats. Levels of saturated fatty acids in sperm were also negatively related to sperm concentration (r= -0.53), but saturated fat intake was unrelated to sperm levels (r = 0.09). Higher intake of omega-3 polyunsaturated fats was related to a more favorable sperm morphology. Men in the highest third of omega-3 fatty acids had 1.9% (0.4-3.5%) higher normal morphology than men in the lowest third (P(trend) = 0.02). CONCLUSIONS: In this preliminary cross-sectional study, high intake of saturated fats was negatively related to sperm concentration whereas higher intake of omega-3 fats was positively related to sperm morphology. Further, studies with larger samples are now required to confirm these findings.