Objective: To evaluate cumulative live birth after preimplantation genetic testing for aneuploidy (PGT-A) with next generation sequencing (NGS) compared with morphology alone among patients aged 21-40 years undergoing single blastocyst transfer. Design: Retrospective cohort study. Subjects: Patients aged 21-40 years undergoing first autologous retrieval cycles resulting in >= 5 fertilized oocytes, with subsequent single blastocyst transfer in Society for Assisted Reproductive Technology clinics from 2016-2019. Exposure: PGT-A using NGS. Main outcome measures: The primary outcome was cumulative live birth per retrieval. Secondary outcomes included clinical pregnancy, miscarriage, and live birth per transfer. Results: A total of 56,469 retrieval cycles were included in the analysis. Retrieval cycles were stratified based on age (<35, 35-37, and 38-40 years) and exposure to PGT-A with NGS. Modified Poisson regression modeling was used to evaluate the association between PGT-A and cumulative live birth per retrieval while controlling for covariates. In this cohort, most cycles did not use PGT-A (n = 49,608; 88%). After adjusting for covariates, the use of PGT-A was associated with a slightly lower cumulative live birth in individuals aged <35 years (risk ratio [RR]: 0.96; 95% CI: 0.93-0.99) compared with no PGT, but higher cumulative live birth in ages 35-37 years (RR: 1.04; 95% CI: 1.00-1.08), and 38-40 years (RR: 1.14; 95% CI: 1.07-1.20). A subgroup analysis limited to freeze-all cycles (n = 29,041) showed that PGT-A was associated with higher cumulative live birth in individuals aged >= 35 years and was similar to no PGT in individuals aged <35 years. Miscarriage was significantly less likely in individuals aged >= 35 years using PGT-A compared with no PGT-A. Conclusion: In this large national database study, success rates in cycles using PGT-A were dependent on age. Cumulative live birth was observed to be significantly less likely in PGT-A cycles among individuals aged <35 years and more likely among individuals aged 38-40 years, compared with no PGT-A. In individuals with no fresh transfer, results were similar. Moreover, miscarriage was significantly less likely with PGT-A among individuals aged 35-40 years in a subgroup analysis of freeze-all cycles.

To evaluate cumulative live birth rate (CLBR) following PGT-A vs. non-PGT-A cycles among women aged 21-40 years undergoing single blastocyst transfer. This was a retrospective cohort study of the 2016-2019 SART database. First, autologous cycles in patients 21-40 with single blastocyst transfer with or without PGT-A using NGS were included. Cycles with 2PN < 5, use of gestational carrier, mixed embryos from multiple stimulation cycles, PGT for reasons other than aneuploidy, and recurrent pregnancy loss were excluded. Cycles with no transfer due to lack of euploid embryos were included. Primary outcome was CLBR, defined as live birth from up to three transfers for each retrieval cycle. A logistic regression model was used controlling for age, race, BMI, nulliparity, smoking, infertility diagnosis, and total number of blastocysts. A sensitivity analysis was performed among patients with no fresh transfer, limiting to freeze all cycles in both groups. The results are shown per age group. The odds of CLBR were significantly lower in the PGT-A group in women < 35, higher in ages 35-37 (p = 0.06), and significantly higher in women 38-40 years (Table). The sensitivity analysis using freeze-all cycles only (n=29,041) showed significantly higher odds of CLBR with PGT-A in women ≥ 35 and no difference in women < 35. The odds of miscarriage were significantly lower in the PGT-A cycles in women ≥ 35 and in all age groups in the sensitivity analysis. CLBR is significantly higher in PGT-A compared to non-PGT-A cycles for women ≥ 35. PGT-A does not improve CLBR for those < 35.

Since the introduction of gonadotropins for ovarian stimulation for the purpose of multiple follicular recruitment for in vitro fertilization (IVF), it was recognized that patients respond differently to the same stimulation protocol and dose. Some respond with a large number of eggs, some with moderate, some with low, and some without any developing follicles. There are no universally accepted definitions for these patients. Over the years, multiple approaches have been used to increase the number of eggs in low responders. Most of these approaches involve increasing the dose of medications or adding adjuvant and often expensive therapies. Most of these therapies have not been subjected to well-designed randomized controlled trials. Yet, many of these therapies are still used commonly, mostly in the United States, despite the lack of clear efficacy. The main outcome for these challenging patients is the live birth rate and not the ovarian reserve markers or the number of retrieved oocytes. Converting a low responder to a moderate or high category is not achievable in the large majority of cases. As such, the main aim of treatment for these patients is not to increase the burden of treatment, in terms of cost, stress, and office visits. We are all too familiar with adjuvant interventions in reproductive medicine, such as human growth hormone (1Cozzolino M. Cecchino G.N. Troiano G. Romanelli C. Growth hormone cotreatment for poor responders undergoing in vitro fertilization cycles: a systematic review and meta-analysis.Fertil Steril. 2020; 114: 97-109Google Scholar), which have been proposed to improve response to controlled ovarian stimulation and live birth rates among poor responders. Unfortunately, we have yet to find an adjuvant intervention that provides clear and high-quality evidence demonstrating improvement in live birth rates (2Kyrou D. Kolibianakis E.M. Venetis C.A. Papanikolaou E.G. Bontis J. Tarlatzis B.C. How to improve the probability of pregnancy in poor responders undergoing in vitro fertilization: a systematic review and meta-analysis.Fertil Steril. 2009; 91: 749-766Google Scholar, 3Sood A. Mohiyiddeen G. Ahmad G. Fitzgerald C. Watson A. Mohiyiddeen L. Growth hormone for in vitro fertilisation (IVF).Cochrane Database Syst Rev. 2021; 11CD000099Google Scholar). Considerable research has been conducted comparing stimulation protocols for poor responders with no clear evidence of superiority. It is important to consider circumstances where “less is more,” particularly with poor responders. For example, minimal stimulation protocols for poor responders have similar outcomes to standard protocols with significantly lower financial burden for patients (4Practice Committee of the American Society for Reproductive MedicineComparison of pregnancy rates for poor responders using IVF with mild ovarian stimulation versus conventional IVF: a guideline.Fertil Steril. 2018; 109: 993-999Google Scholar). Mild/minimal stimulation protocols significantly decrease the cost and allow patients to have repeat stimulations instead of draining their resources with 1 expensive treatment. Despite the endorsement of the Practice Committee of the American Society for Reproductive Medicine for the use of these protocols and providing evidence of similar efficacy to standard protocols, physicians have been slow or resistant to the adoption of these treatments. Diaz-Garcia et al. (5Díaz-García C. Herraiz S. Pamplona L. Subirá J. Soriano M.J. Simon C. et al.Follicular activation in women previously diagnosed with poor ovarian response: a randomized, controlled trial.Fertil Steril. 2022; 117: 747-755Google Scholar) present a well-designed randomized controlled trial with parallel assignment of 34 women with poor ovarian response according to the European Society of Human Reproduction and Embryology criteria. Patients were randomized to laparoscopic ovarian fragmentation in only 1 ovary vs. no intervention in the control group. This allowed for women receiving intervention to serve as their own internal controls while being compared with women who did not receive the intervention. After the intervention, ovarian reserve biomarkers were collected biweekly for 6 months. Ovarian stimulation for IVF was initiated after a doubling of antral follicle count (AFC) or at the end of the follow-up period. The primary outcome was number of metaphase II (MII) oocytes. The secondary outcomes included AFC, serum antimüllerian hormone, and reproductive outcomes (e.g., live birth rate). Exploratory outcomes included surgical results and gene expression/protein expression analyses reflecting Hippo pathway inhibition (YAP phosphorylation and expression of YAP target proteins, CCN and BIRC) (5Díaz-García C. Herraiz S. Pamplona L. Subirá J. Soriano M.J. Simon C. et al.Follicular activation in women previously diagnosed with poor ovarian response: a randomized, controlled trial.Fertil Steril. 2022; 117: 747-755Google Scholar). Ovarian fragmentation for follicular activation (OFFA) was associated with statistically significant increases in the intervention ovary compared with the control ovary and total AFC in the OFFA group compared with the control group. Ovarian fragmentation for follicular activation did not improve serum levels of antimüllerian hormone or follicle-stimulating hormone. In the control group, 33 MII oocytes were retrieved, and 18 embryo transfers were performed with pregnancy and live birth rates of 20% and 18.7%, respectively. In the OFFA group, 23 MII oocytes were retrieved, and 11 embryo transfers were performed with pregnancy and live birth rates of 13.3% and 6.7%, respectively. Among those who underwent OFFA, molecular expression analysis confirmed an 18.8% reduction in phosphor-YAP/YAP ratio and BIRC and CCN overexpression. The study investigators concluded that among women with poor ovarian response, OFFA resulted in an increase in AFC but did not modify IVF outcomes compared with controls. When considering the findings of this investigation, there are important limitations that warrant discussion. A major limitation in study design is related to differences in time to stimulation. The wait time to start the IVF treatment was on average 2 months earlier in the surgical group compared with that in the control group. Although the investigators stress that this was not statistically significant, it could be clinically significant for the control group because the wait time was 155 days. It is also unclear why the investigators expected an increase in the AFC over time in the control group. The number of mature eggs was lower, although not significant, in the treatment group than in the control group as well as the live birth rate. This study was not adequately powered to detect differences in live birth rate, which is the most important outcome for our patients. Despite known endometriosis being an exclusion criterion, 26% of participants were found to have endometriosis at the time of surgery. It is unclear how this diagnosis could affect ovarian stimulation. Rightfully, the study investigators conclude that this intervention should not be recommended given findings showing lack of benefit. Ovarian fragmentation for follicular activation involves a complex laparoscopic procedure that requires a high degree of surgical expertise. In addition, this procedure will require the presence of laboratory personnel trained in this new technique. Furthermore, such an intervention exposes patients to an increased financial cost and risk of surgical complications. Although there are patients who are willing to pay for expensive adjuvant interventions with hopes of improving their fertility treatment outcomes, it may not always be in their best interest. It is our duty as fertility specialists to rigorously evaluate emerging therapies and interventions to provide high-quality, evidence-based care. In this case, we clearly recognize that the benefits of this adjuvant intervention do not justify the potential risks and financial costs. Therefore, it should not be recommended for the improvement of IVF outcomes among poor responders. Follicular activation in women previously diagnosed with poor ovarian response: a randomized, controlled trialFertility and SterilityVol. 117Issue 4PreviewTo investigate whether ovarian fragmentation for follicular activation (OFFA) improves ovarian reserve markers and in vitro fertilization (IVF) outcomes in women with poor ovarian response (POR). Full-Text PDF

Importance Up to 4% of all births in developed nations involve assisted reproductive technology (ART), along with other fertility treatment modalities. Thus, ART pregnancies constitute an important epidemiologic population with a known increased risk of congenital anomalies. In this review, we summarize current fertility treatment modalities and their associated risk of congenital anomalies. Objective To review the risk of birth defects among pregnancies conceived with ART and other fertility treatments. Evidence Acquisition Articles were obtained from PubMed and the American College of Obstetricians and Gynecologists and American Society of Reproductive Medicine committee opinions. Results In vitro fertilization has been associated with a 25% to 50% increased risk of birth defects, including abnormalities of these organ systems: cardiovascular (25%–40% of anomalies), genitourinary (10%–60%), gastrointestinal (10%–20%), and musculoskeletal (10%–35%). Although the data are mixed, intracytoplasmic sperm injection has also been found to be associated with an increased risk of defects, particularly hypospadias, when compared with conventional in vitro fertilization. The risk among fresh versus frozen cycles and cleavage stage versus blastocyst transfers remains uncertain. There appears to be no significant added risk with preimplantation genetic testing, although more studies are needed. Ovulation induction with oral agents appears safe and not associated with an increased risk of anomalies. Oocyte cryopreservation also appears safe, but the data are still limited, requiring future investigation. Conclusions and Relevance While the relative risk of birth defects among ART pregnancies is increased when compared with spontaneous conceptions, the absolute risk remains low. There are no standard screening recommendations for ART pregnancies. Per the American College of Obstetricians and Gynecologists, patients who have undergone ART should be counseled regarding the risk of birth defects and available antenatal evaluation, including fetal echocardiogram and detailed ultrasound evaluation. Target Audience Obstetricians and gynecologists, family physicians. Learning Objectives Following completion of this CME article, readers should be better able to assess risk factors for birth defects among individuals undergoing fertility treatment; explain available antenatal screening modalities for detection of common birth defects associated with ART; and identify available resources and recommendations on risk factors for birth defects associated with infertility treatment.

The goal of ovarian stimulation for in vitro fertilization (IVF) is to recruit multiple oocytes for fertilization. The ovarian stimulation process can be a stressful experience for the patient with multiple office visits, blood draws, and ultrasounds in addition to the high cost of medications. High doses of gonadotropins given for a prolonged time are associated not only with lower clinical pregnancy rates and live births, but also with a higher risk of spontaneous miscarriage. Mild or minimal ovarian stimulation protocols attempt to reduce costs, improve patient compliance, and enhance endometrial receptivity, corpus luteum function, and oocyte and embryo quality. Mild stimulation strategies are an acceptable option for many infertile couples interested in lower costs, risks, and a more patient friendly approach. Physicians should counsel patients that the aim of IVF is to have a healthy live birth, and not necessarily to obtain as many oocytes and embryos as possible.

Our main objective was to determine the key purchase criteria (KPC) of US consumers of IVF, particularly for the decision points of proceeding with IVF and choosing REI clinics. A cross-sectional survey was developed in Qualtrics. From June-August 2020, respondents were recruited for a small monetary incentive to complete the survey via the Pollfish platform. Additional consumers from Instagram followers of #IVF were surveyed to ensure invested user opinions. Individuals screened in if they were US residents and reproductive-aged women, who had conceived/attempted to in the last 3 years. Two discrete survey paths were created, one for IVF-adopters and non-adopters. Data analysis was performed using SAS. A sub-analysis of qualitative responses was also conducted. In total, 695 consumers were included in the analysis. When ranking top 3 considerations in selecting an REI/clinic, over 60% of IVF-adopters reported good success rates, followed by the clinic accepting their insurance. The next most important KPCs were the doctor's personality, recommendations by friends/family, proximity, referral from their OB/GYN, and online reviews (e.g. Yelp). When ranking top 3 primary sources of information to research REIs/IVF clinics, over 40% reported the Society of Assisted Reproductive Technologies (SART) website, followed closely by clinic websites, their OB/GYN, online reviews, and Google search. Regarding likelihood to recommend IVF and their clinic, Net Promoter Scores, which track consumer loyalty (% promoters - % detractors), were 19.6 and 40.9, respectively. Common themes that consumers shared that pivoted their overall satisfaction with IVF or their clinic centered on outcomes, the doctor's bedside manner, personalized treatment, and communication; cost was not a critical pivot point. Compared to non-adopters, adopters were more likely to have IVF covered by employers' insurance policy or have state mandates, while more non-adopters would need to pay out-of-pocket. 60% of non-adopters chose not to pursue IVF due to cost, with 43% due to insurance not covering IVF. The identified KPC suggest that when deciding on proceeding with IVF or choosing an infertility clinic, the two gating criteria are outcomes and insurance coverage. What further differentiates the clinics are the REI's personality, proximity, being vetted by OB/GYNs, and online reviews. With over 40% of consumers using SART, this implies a highly educated sophisticated buyer. While satisfaction was driven by outcomes, ineffective communication, lack of personalized care, and poor bedside manner greatly impact consumer dissatisfaction, unlike cost. For non-adopters, the key deterrents to proceeding are cost and insurance coverage.

Importance: Turner syndrome (TS) is one of the most common chromosomal abnormalities in women. The condition is characterized by gonadal dysgenesis and is associated with structural cardiac abnormalities. Assisted reproductive technology with oocyte donation may be successful but places women with TS at increased risk of aortic dissection and death.Objective: To summarize all cases of aortic dissection associated with pregnancy in women with TS and provide guidance regarding the safety of pregnancy.Evidence Acquisition: Systematic review of PubMed for reports of women with TS, aortic dissection, and pregnancy.Results: There are 14 total reported cases of aortic dissection associated with pregnancy in women with TS. Ten of these cases occurred during pregnancy or in the first month postpartum. The majority of affected pregnancies resulted from oocyte donation, 2 of which were multiple gestations. Two women had a documented history of hypertension, and 3 pregnancies were complicated by preeclampsia. Bicuspid aortic valve and coarctation of the aorta were the most common associated cardiac anomalies. More than half of women had some degree of aortic dilatation. Two women had no identifiable risk factors.Conclusions and Relevance: Women with TS who desire pregnancy must be thoroughly counseled regarding the increased risk of aortic dissection during pregnancy and postpartum. Preconception consultation with maternal-fetal medicine, reproductive endocrinology, and cardiology is necessary along with a comprehensive physical evaluation. If women with TS choose to pursue pregnancy, they require rigorous cardiac monitoring each trimester during pregnancy and postpartum.Target Audience: Obstetricians and gynecologists, family physicians.Learning Objectives: After completing this activity, the learner should be able to describe the presentation of Turner syndrome, including the associated cardiovascular anomalies; identify the increased risk of aortic dissection associated with pregnancy in women with Turner syndrome; and recommend appropriate preconception consultation and optimal cardiac monitoring.

Objective: Oocyte donation has optimized our understanding of ovarian stimulation. Increasing the follicle-stimulating hormone (FSH) dose has been shown to adversely affect live birth rates in autologous cycles. Our objective is to assess whether this relationship holds true within the donor/recipient population. Design: Retrospective cohort study. Setting: Not applicable. Patients: Data from 2014-2016 included 8,627 fresh donor cycles. Interventions: None. Main outcome measures: Live birth, clinical pregnancy, and miscarriage rates. Results: The mean donor age +/- standard deviation (SD) was 25.8 +/- 2.8 years. Donors underwent a median of 16 days (interquartile range (IDRI 12, 19) of stimulation with a median (IQR) total FSH dose and daily dose of 2,350.0 (1,800.0, 3,025.0) and 153.8 (113.2, 205.0) IU, respectively. The live birth rate was 56.7% per transfer. For every 500-unit increase in FSH dose, there was a 3% reduction in the odds of a live birth (odds ratio [OR) 0.97; 95% confidence interval 0.95, 0.99), and a 3% reduction in the odds of a clinical pregnancy (OR 0.97; 95% confidence interval 0.95, 0.99). Days of stimulation and average daily dose were not significantly associated with live birth or clinical pregnancy. No significant association was found between miscarriage rates and total FSH dose, days of stimulation, or average daily dose. Conclusion: This is a novel report of a negative association of total FSH dosage on fresh IVF live births, performed in the donor population to control for oocyte source and endometrial receptivity. (C) 2020 by American Society for Reproductive Medicine.

Background In patients with low numbers of embryos, there is not yet consensus on whether to extend culture to the blastocyst stage, especially due to the risk that some or all of the embryos will not make it to the blastocyst stage. The objective of our study was to evaluate pregnancy outcomes in patients with a low number of fertilized oocytes (< 4), comparing single blastocyst transfer to one or more cleavage embryo transfer. Results We analyzed 6795 cycles from the 2014–2105 Society for Assisted Reproductive Technology (SART) registry. All patients were ≤ 38 years old, had less than four fertilized oocytes, and were undergoing first fresh in vitro fertilization (IVF) transfer. Primary outcomes were clinical pregnancy (CP), live birth (LB), and miscarriage rate in both cleavage stage transfer and single blastocyst transfer. A secondary outcome was the rate of twin gestation. The comparison of interest in day of transfer included (1) single blastocyst vs single cleavage and (2) single blastocyst vs multiple cleavage stage. The association between day of transfer and primary outcome was investigated using logistic regression, controlling for the age, race/ethnicity, BMI, smoking, gravidity, parity, infertility diagnoses, and assisted hatching. Single blastocyst transfer was associated with an increased odds of CP (adjusted OR 2.03) and LB (adjusted OR 1.86) when compared to single cleavage transfer, and no statistically significant association was observed when comparing single blastocyst transfer to multiple cleavage embryo transfer for CP (adjusted OR 0.94) and LB (adjusted OR = 0.88). The odds of having twins among single blastocyst transfer was significantly lower compared to those odds that among multiple cleavage stage transfer (unadjusted OR 0.09). Conclusions While pregnancy outcomes are similar between single blastocyst and multiple cleavage embryo transfer, the twin rate is reduced significantly among the single blastocyst transfers in patients with a low number of fertilized oocytes.

Turner syndrome (TS) is one of the most common chromosomal abnormalities in women. The condition is characterized by gonadal dysgenesis and is associated with structural cardiac abnormalities. Assisted reproductive technology with oocyte donation may be successful but places women with TS at increased risk of aortic dissection and death.To summarize all cases of aortic dissection associated with pregnancy in women with TS and provide guidance regarding the safety of pregnancy.Systematic review of PubMed for reports of women with TS, aortic dissection, and pregnancy.There are 14 total reported cases of aortic dissection associated with pregnancy in women with TS. Ten of these cases occurred during pregnancy or in the first month postpartum. The majority of affected pregnancies resulted from oocyte donation, 2 of which were multiple gestations. Two women had a documented history of hypertension, and 3 pregnancies were complicated by preeclampsia. Bicuspid aortic valve and coarctation of the aorta were the most common associated cardiac anomalies. More than half of women had some degree of aortic dilatation. Two women had no identifiable risk factors.Women with TS who desire pregnancy must be thoroughly counseled regarding the increased risk of aortic dissection during pregnancy and postpartum. Preconception consultation with maternal-fetal medicine, reproductive endocrinology, and cardiology is necessary along with a comprehensive physical evaluation. If women with TS choose to pursue pregnancy, they require rigorous cardiac monitoring each trimester during pregnancy and postpartum.

Background To evaluate the association of patient and IVF cycle characteristics with blastulation rate and formation of high-quality blastocysts Results We analyzed autologous blastocyst cycles from 2013 to 2017. Cycles were subdivided into low (< 33%), intermediate (33–66%), and high (> 66%) blastulation rates. Embryo quality was assigned by embryologists using Gardner Criteria. R statistical package was used, and the blastulation groups were compared using analysis of variance (ANOVA) for continuous variables and chi-squared tests for categorical variables. The Bonferroni correction was used to adjust for multiple comparisons. One hundred seventeen IVF cycles met our inclusion criteria. Of these, 20 (17.1%) had low, 74 (63.2%) had intermediate, and 23 (19.7%) had high blastulation rates. Low blastulation rate was associated with a lower number of blastocysts, including fewer high-quality blastocysts. The mean number of oocytes retrieved was highest (18.1) in the group with the lowest blastulation rate, and lowest (13.4) in those with the highest blastulation rate, although this did not reach statistical significance. There were no significant differences between blastulation rates and age, gravidity, prior live birth, anti-mullerian hormone, estradiol and progesterone levels on the day of ovulation trigger, follicle-stimulating hormone dose, or fertility diagnosis. Conclusions High blastulation rate is associated with a greater number of blastocysts, including a greater number of high-quality blastocysts. Higher oocyte yield, however, is not associated with improved blastulation rates. Blastulation rates, blastocyst number, and quality remain difficult to predict based on cycle characteristics alone, and oocyte yield may not be an accurate predictor of either outcome.

As part of the objectives set out in the Patient Protection and Affordable Care Act of 2010, the Institute of Medicine (IOM) published in its report on the future of nursing (1Committee on the Robert Wood Johnson Foundation Initiative on the Future of NursingThe future of nursing: focus on education. Institute of Medicine of the National Academies, 2010http://www.nationalacademies.org/hmd/Reports/2010/The-Future-of-Nursing-Leading-Change-Advancing-Health/Report-Brief-Education.aspxGoogle Scholar) a section entitled “The Future of Nursing: Leading Change, Advancing Health.” Within that section, the committee recognized the need to focus on higher education for nurses, specifically to promote “lifelong learning” and “the need for highly educated nurses” (1Committee on the Robert Wood Johnson Foundation Initiative on the Future of NursingThe future of nursing: focus on education. Institute of Medicine of the National Academies, 2010http://www.nationalacademies.org/hmd/Reports/2010/The-Future-of-Nursing-Leading-Change-Advancing-Health/Report-Brief-Education.aspxGoogle Scholar). According to the World Health Organization (WHO), nurses account for nearly 50% of the global health workforce (2World Health Organization Nursing and midwifery: WHO fact sheet. February 2018.https://www.who.int/mediacentre/factsheets/nursing-midwifery/en/Google Scholar), and within the United States there is a projected need for an additional 203,700 nurses each year through 2026 (3Bureau of Labor Statistics, U.S. Department of LaborOccupational outlook handbook, registered nurses.https://www.bls.gov/ooh/healthcare/registered-nurses.htmGoogle Scholar). These statistics reinforce how the nursing workforce is an integral part of our health care system, with nurses at the front lines of patient care, especially in the field of reproductive endocrinology and infertility. The article by Catherino et al. (4Catherino A. Halupa C. Sharara F.I. Bromer J.G. et al.Evaluation of an embryology and genetic testing patient counseling education intervention for reproductive endocrinology nurses.Fertil Steril. 2019; 112: 275-282Abstract Full Text Full Text PDF Scopus (2) Google Scholar) examines a structured educational intervention for infertility nurses that aims to improve their understanding of embryology and genetics in patient outcomes. The article highlights several of the issues in the IOM's 2010 report. The authors note that even though infertility nurses are an important part of a patient's in vitro fertilization (IVF) process, they are often “unfamiliar with complex embryo morphology and genetic testing results,” thus “limiting their ability to counsel effectively” (5Mitchell A. Mittelstaedt M.E. Wagner C. A survey of nurses who practice in infertility settings.J Obstet Gynecol Neonat Nurs. 2005; 34: 561-568Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar). The article also addresses the informal mentoring received by infertility nurses, who are often transitioning from working with labor and delivery. Their lack of formalized training in IVF is particularly apparent in the areas of embryology and genetics. The authors initiated an educational intervention composed of 25-minute “Lunch and Learn” topics focusing on both embryology laboratory and reproductive genetic terms, definitions, and processes. Two weeks after the intervention, 66% of the nurses felt more confident in counseling their patients on the aforementioned topics, which is notable given that the nurses in the study cited patient counseling to represent the majority of their clinical time (4Catherino A. Halupa C. Sharara F.I. Bromer J.G. et al.Evaluation of an embryology and genetic testing patient counseling education intervention for reproductive endocrinology nurses.Fertil Steril. 2019; 112: 275-282Abstract Full Text Full Text PDF Scopus (2) Google Scholar). Given that study participation was completely voluntary, the authors demonstrated not only that infertility nurses have a desire to learn but also that learning improved their confidence in counseling patients. This finding should not be discounted. As the field of medicine evolves amid the increasingly complex web of the U.S. health care system, physicians are unfortunately spending less time with our patients. Infertility nurses develop vital relationships with our patients, and regardless of whether it is within their scope of practice or the realm of their formalized training, they field the majority of the patients' questions. Educating nurses properly can empower them to correctly counsel patients in some of their most vulnerable moments. As the study's authors mentioned, physicians may inform patients about the specifics of genetic testing, but they simply do not get the same amount of face-to-face time as the nurses. However, although this educational intervention is overwhelmingly positive, it should be noted that formalized learning should not stop after several sessions. Like physicians, infertility nurses should engage in lifelong learning because our field is constantly evolving. Continued education is not only preferable but is recommended by the IOM. Infertility nurses should be included in all educational efforts taking place in our clinics, and they should be offered additional continuing medical education (CME). Also, IVF clinics should consider paying for their nurses to become members of the American Society for Reproductive Medicine (ASRM), currently $150 per year with online access provided to Fertility and Sterility. Key nursing staff should also be encouraged to join the ASRM Nurses' Professional Group and to attend the annual ASRM meeting at least every 2 to 3 years, with costs covered by the clinic. This is an excellent investment that will provide positive dividends with patients in terms of success rates and safety. This article is certainly a step in the right direction. Formalized training for our nurses is an aim that has been emphasized for over a decade—and it is time to start putting the gears in motion. Evaluation of an embryology and genetic testing patient counseling education intervention for reproductive endocrinology nursesFertility and SterilityVol. 112Issue 2PreviewTo study the impact of an educational program on the knowledge base of reproductive endocrinology nurses on embryology and genetics topics to determine both improvement in knowledge and confidence in the nurses' ability to counsel patients on such topics. Full-Text PDF Open Archive

There has been a trend in IVF cycles to culture to blastocyst (day 5-6) as blastocyst transfer has been shown to have higher clinical pregnancy rates and live birth rates compared to cleavage stage transfer (day 2-3). Practitioners are currently better able to choose a euploid embryo based on blastocyst morphology, and a blastocyst transfer is more physiologic as this is the time when an embryo enters the uterus in a natural cycle. However, there is always the risk that some or all of the embryos will not make it to the blastocyst stage. In a study of 142 patients that received extended culture, 22.5% of the embryos did not survive the extended culture [1]. Thus in patients with low numbers of embryos, there is not yet consensus on whether to extend these embryos to blastocyst. To evaluate pregnancy outcomes in patients with a low number of fertilized oocytes (<4), comparing single blastocyst transfer to one or more cleavage embryo transfer We analyzed 6,795 cycles from the 2014-2105 SART registry in a retrospective cohort study. All patients were ≤38 years of age, had less than 4 fertilized oocytes, and were undergoing first fresh IVF transfer. Donor oocyte cycles and patients undergoing preimplantation genetic testing were excluded. Primary outcomes were CP, LB, and miscarriage rate in both cleavage stage transfer and single blastocyst transfer. Student's t test and Wilcoxon rank sum test were used to compare the 2 groups for continuous variables while Chi-square test was used for categorical variables. Furthermore, we investigated the association between day of transfer and each outcome using logistic regression while controlling for the same confounders (age, race/ethnicity, BMI, smoking, gravidity, parity, and infertility diagnoses). All statistical analyses were conducted using R version 3.4.3 (Vienna, Austria) and SAS 9.4 (SAS Institute, Cary, NC). Among all cycles in the cohort, the CP, LB, and miscarriage rate was 38%, 31%, and 16%. Single blastocyst transfer was associated with higher odds of clinical pregnancy (OR = 2.52; 95% CI = 2.25, 2.81; p < 0.0001) and live birth (OR = 2.29; 95% CI = 2.05, 2.57; p < 0.0001) compared to one or more cleavage transfer. The odds of having twins among single blastocyst transfer was significantly lower than that among cleavage stage transfer (OR 0.12; 95% CI= 0.07, 0.22; p<0.0001).Table 1IVF cycle and characteristics of cleavage stage versus blastocyst transfer.Cleavage transfer (N = 5,657)Blastocyst transfer (N = 1,138)OR adjusted AAdjusted for age, BMI, smoker, race, parity, gravidity, infertility diagnoses, and assisted hatching.Age, years, mean ± SD33.6 ± 3.333 ± 3.4BMI kg/m2, mean ± SD26.3 ± 6.126 ± 5.9FSH dose IU, mean ± SD3602.4 ± 1778.53601.9 ± 1776.8Number of available oocytes, median (IQR)5 (3,8)6 (4,9)Mean number of embryos transferred1.7 ± 0.61 ± 0Clinical pregnancy rate38%43%1.84 (1.57, 2.17)BP < 0.0001Live birth rate32%35%1.67 (1.41, 1.98)BP < 0.0001Miscarriage rate15%17%1.16 (0.82, 1.65)BP < 0.0001Singleton rate CSingleton rate and twin rate only included pregnancies with a documented fetal heartbeat.80%97%8.68 (4.95, 15.22)Twins rate CSingleton rate and twin rate only included pregnancies with a documented fetal heartbeat.19%3%0.12 (0.07, 0.22)A Adjusted for age, BMI, smoker, race, parity, gravidity, infertility diagnoses, and assisted hatching.B P < 0.0001C Singleton rate and twin rate only included pregnancies with a documented fetal heartbeat. Open table in a new tab Pregnancy outcomes (CP, LB) improve significantly with single blastocyst transfer compared to one or more cleavage embryo transfer in patients with <4 fertilized oocytes. Furthermore, the twin rate is significantly lower. IVF programs and patients are strongly encouraged to pursue extended culture with single embryo transfer if more than one embryo with good morphology is available on day 3.

Objective: To study the association between the total number of fertilized oocytes available and pregnancy outcomes in first fresh IVF cycles with a single blastocyst transfer. Design: Retrospective cohort study. Setting: Not applicable. Patient(s): A total of 15,803 patients from SART reporting fertility clinics. Intervention(s): None. Main Outcome Measure(s): Primary outcomes were clinical pregnancy (CP), live birth (LB), and miscarriage rates. Logistic regression was used to investigate the association between the number of fertilized eggs and each outcome. Result(s): The median number of total oocytes was 15, and the median number of fertilized oocytes was nine. The odds of a clinical pregnancy were 8% higher for each additional fertilized oocyte up to nine (odds ratio [OR] 1.08; 95% confidence interval [CI] 1.07-1.10) and declined by 9% for every additional fertilized oocyte after nine (OR 0.91; 95% CI 0.89-0.94). Similarly, the odds of an LB was 8% higher for every additional fertilized oocyte up to none (OR 1.08; 95% CI 1.06-1.10) and declined by 8% for every additional fertilized oocyte over nine (OR 0.92; 95% CI 0.90-0.94). Conclusion(s): Odds of pregnancy outcomes (CP, LB) increase significantly with every additional fertilized oocyte up to nine, and CP and LB decline after that in first fresh autologous cycles with a single blastocyst transfer. ((C) 2019 by American Society for Reproductive Medicine.)

Objective: To study the association between the number of blastocysts available and pregnancy outcomes in first fresh autologous single blastocyst transfer cycles. Design: Retrospective cohort study. Setting: Not applicable. Patient(s): Patients from the Society for Assisted Reproductive Technology reporting fertility clinics (n=16,666). Interventions(s): None. Main Outcome Measure(s): Primary outcomes were clinical pregnancy (CP), live birth (LB), and miscarriage rates. Logistic regression was used to investigate the association between the number of blastocysts and each outcome. Result(s): When comparing fresh single blastocyst transfer rates, the odds of a positive pregnancy outcome (CP) increased significantly with each additional supernumerary blastocyst up to five and declined by 2% for every additional blastocyst after five. Similarly, the odds of an LB was 17% higher for each additional blastocyst up to five and declined by 2% for every additional blastocyst after five. There was no significant association between blastocyst number and miscarriage rate. Conclusion(s): Odds of positive pregnancy outcomes (CP, LB) increased significantly with every additional blastocyst up to five, but declined after that, in first fresh autologous cycles with single-blastocyst transfer. The decline after five may be explained by a detrimental effect on endometrial receptivity in patients with a large number of oocytes or inadequate selection of the best embryo for transfer based on morphology alone. (C) 2019 by American Society for Reproductive Medicine.)

To evaluate whether the total number of fertilized oocytes available affects pregnancy outcomes in first fresh IVF cycles with a single blastocyst transfer. Retrospective cohort study. We analyzed 16,032 first fresh IVF cycles from the 2014-2015 SART registry. All patients were = 38 years old and undergoing first fresh IVF transfer with a single blastocyst. Cycles with conventional insemination and intracytoplasmic sperm injection were included. Donor oocyte cycles and patients undergoing preimplantation genetic testing were excluded. Primary outcomes were CP, LB, and miscarriage rates. Logistic regression was used to investigate the association between the number of fertilized eggs and each outcome. Using linear splines, a final logistic regression model was used to model each outcome while controlling for confounders (age, race/ethnicity, BMI, smoker, gravidity, parity, and infertility diagnoses). All statistical analyses were conducted using R version 3.4.3 (Vienna, Austria) and SAS 9.4 (SAS Institute, Cary, NC). The mean age +/- SD of the patients was 31.8 +/ 3.3. The median number of oocytes (IQR) was 15 (10, 20) and the median number of fertilized oocytes (IQR) was 9 (6, 13). Among all cycles in the cohort, the CP, LB and miscarriage rates were 57%, 49%, and 13% respectively. The odds of a clinical pregnancy was 8% higher for each additional fertilized oocyte up to 9 (OR = 1.08; 95% CI = 1.07, 1.10; p < 0.0001) and declined by 1% for every additional fertilized oocyte after 9 (OR = 0.99; 95% CI = 0.98, 0.999; p = 0.02). Similarly, the odds of a live birth was 8% higher for every additional fertilized oocyte up to 9 (OR = 1.08; 95% CI = 1.06, 1.10; p < 0.0001) and trended downward for every additional fertilized oocyte over 9 (OR = 0.99; 95% CI = 0.98, 1.00; p = 0.06). There was no significant association between the number of fertilized oocytes and miscarriage rate (OR = 1.00; 95% CI = 0.98, 1.01; p = 0.51). Pregnancy outcomes (CP, LB) improve significantly with every additional fertilized oocyte up to 9 and CP declines after that in first fresh autologous cycles with a single blastocyst transfer. Live birth rate has a downward trend with each additional fertilized oocyte after 9, although this was not statistically significant. The decline after 9 may be explained with a detrimental effect on endometrial receptivity in patients with a large number of oocytes and/or inadequate selection of the best embryo based on morphology alone.

To evaluate whether the total number of blastocysts available affect pregnancy outcomes in first fresh autologous single blastocyst transfer cycles. Retrospective cohort study. We analyzed 16,666 cycles from the 2014-2015 SART registry. All patient were = 40 years old and undergoing first fresh IVF transfer with a single blastocyst. Only cycles with a single blastocyst transfer were included. Donor oocyte cycles and patients undergoing preimplantation genetic testing were excluded. The total number of blastocysts included those that were transferred and cryopreserved. Primary outcomes were CP, LB, and miscarriage rates. Logistic regression was implemented to model the number of blastocyst embryos on each primary outcome. Using linear splines, a final logistic regression model was used to model each outcome while controlling for confounders (age, race/ethnicity, BMI, smoker, gravidity, parity, and infertility diagnoses). Statistical analyses were conducted using R version 3.4.3 (Vienna, Austria) and SAS 9.4 (SAS Institute, Cary, NC). 20% of the cycles had only a single blastocyst, and the proportion with more than 10 blastocysts decreased dramatically. Among all cycles in the cohort, the CP, LB, and miscarriage rates were 56%, 48%, and 14% respectively. The odds of a clinical pregnancy was 18% higher for each additional blastocyst up to 5 (OR = 1.18; 95% CI = 1.15, 1.21; p < 0.0001) and declined by 2% for every additional blastocyst after 5 (OR = 0.98; 95% CI = 0.97, 0.99; p = 0.05). Similarly, the odds of a LB was 17% higher for each additional blastocyst up to 5 (OR = 1.17; 95% CI = 1.14, 1.20; p < 0.0001) and declined by 2% for every additional blastocyst after 5 (OR = 0.98; 95% CI = 0.97, 0.998; p = 0.02). There was no significant association between the number of blastocysts and miscarriage rate. Of the pregnancies with a fetal heartbeat, the singleton rate was 98%, and the twin rate was 2%. Pregnancy outcomes (CP, LB) improve significantly with every additional blastocyst up to 5, but decline after that in first fresh autologous cycles with single blastocyst transfer. The decline after 5 may be explained by a detrimental effect on endometrial receptivity in patients with a large number of oocytes and/or inadequate selection of the best embryo for transfer based on morphology alone. Consideration should be given to perform preimplantation genetic screening in patients with more than 5 blastocysts in order to transfer a single euploid embryo.

Objective: To assess in vitro fertilization (IVF) and pregnancy outcomes in patients having their first frozen embryo transfer (FET) after a freeze-all cycle versus similar patients having their first fresh embryo transfer (ET). Design: Retrospective cohort study. Setting: None. Patient(s): Registry data on 82,935 patient cycles from the Society for Assisted Reproductive Technology (SART). Intervention(s): All first fresh autologous IVF cycles were analyzed and compared to first FET cycles after a freeze-all first IVF stimulation. The cycles were subdivided into cohorts based upon the number of oocytes retrieved (OR): 1-5 (low), 6-14 (intermediate), and 15+ (high responders). Univariate analyses were performed on cycle characteristics, and multivariable regression analyses were performed on outcome data. Main Outcome Measure(s): Clinical pregnancy rate (CPR) and live-birth rate (LBR). Results: Of the 82,935 cycles analyzed, 69,102 patients had their first fresh transfer, and 13,833 had a first FET. High responders were found to have a higher CPR and LBR in the FET cycles compared with the fresh ET cycles (61.5 vs. 57.4%; 52.0 vs. 48.9%). In intermediate responders, both CPR and LBR were higher after fresh ET compared with FET (49.6% vs. 44.2%; 41.2 vs. 35.3%). Similarly, in low responders, CPR and LBR were higher after fresh compared with FET (33.2% vs. 15.9%; 25.9% vs. 11.5%). Conclusion(s): A freeze-all strategy is beneficial in high responders but not in intermediate or low responders, thus refuting the idea that freeze-all cycles are preferable for all patients. (C) 2018 by American Society for Reproductive Medicine.