In Vitro Fertilization Clinics Research Articles

Cost-effectiveness of in vitro fertilization and controlled ovarian hyperstimulation before and after the COVID-19 outbreak

The goal of the current study is to compare the cost of assisted reproductive technologies (ART) and cost-effectiveness of biotechnology products used in in vitro fertilization (IVF) procedures before and after the COVID-19 outbreak. We performed a cross sectional, observational, retrospective study of patients admitted at the biggest reference IVF clinic in Bulgaria before and after the COVID-19 outbreak with 1237 participants. Information was from patients’ records; micro-costing and cost-effectiveness analysis were performed for evaluating the unit cost per successful pregnancy with different biological products. The analysis showed that the cost of therapy is lower with recombinant gonadotropins (1543.19 BGN) in the pre-COVID-19 period and with the urinary gonadotropins (1534.03 BGN) in the second period. In addition, during the second period we observed higher expenses due to additional costs for cryopreservation. During the pre-pandemic period the less effective therapy (0.14% clinical pregnancies) was the combination therapy, as well as bearing a higher cost (1749.36 BGN). The cost-effective alternative during the first, (ICER= −7000 BGN per successful pregnancy) and the second period (ICER= −2800 BGN per successful pregnancy) is the therapy with recombinant hormones. It was prescribed in 37% of the patients. After the COVID-19 outbreak the overall cost of IVF increased, even though controlled ovarian hyperstimulation cost decreased. Additional procedures are playing а role for this increase. In both periods, before and after the COVID-19 outbreak, short protocols with recombinant hormones appear to be more effective and cost-effective as an alternative.

Association between estradiol levels and clinical outcomes of IVF cycles with single blastocyst embryo transfer

Objective: To determine the correlation of different serum estradiol levels on the trigger day with the clinical and laboratory outcomes of in-vitro fertilization (IVF) cycles comprising a single fresh top-quality blastocyst transfer. Methods: This was a retrospective observational study performed in Morula IVF Clinic Jakarta. Five hundred forty-two women were recruited and grouped according to their serum estradiol levels on the trigger day of follicular maturation as follows: Results: Clinical pregnancy and miscarriage rates did not differ among the groups (P>0.05). Nonetheless, the study demonstrated a positive correlation of the serum estradiol levels with the overall laboratory outcomes including the number of retrieved, mature, and fertilized oocytes, the total sum of derived embryos, and top-quality embryos at cleavage and blastocyst stage (P Conclusions: Although an apparent positive correlation is observed between estradiol levels and laboratory outcomes, serum estradiol level on hCG trigger day is not associated with the clinical outcomes of IVF.

Society for Assisted Reproductive Technology advertising guidelines: How are member clinics doing?

To examine whether Society for Assisted Reproductive Technology (SART) member invitro fertilization (IVF) centers adhere to the Society's new advertising policy, updated in January 2018, and evaluate other services advertised by region, insurance mandate and university affiliation status. Historically, a large percentage of IVF clinics have not adhered to SART guidelines for IVF clinic website advertising and have had variability in how financial incentives and other noncore fertility services are advertised. Cross-sectional study. Not applicable. None. None. Adherence of SART participating websites to objective criteria from the 2018 SART advertising guidelines. All 361 SART participating clinic websites were evaluated. Approximately one third of clinics reported success rate statistics directly on their websites, but only 52.6% of those clinics reported current statistics. Similarly, only 67.5% of SART member clinics included the required disclaimer statement regarding their outcome statistics. Only 10.5% of websites were wholly compliant with SART guidelines regarding presentation of supplemental data. There were no significant differences between academic and nonacademic centers, programs in mandated versus nonmandated states, or East versus West Coast clinics in any of these areas. Many of the SART member websites failed to adhere to core guidelines surrounding reporting IVF clinic success rates. Consideration for additional education and streamlining as well as simplifying success rate advertising guidelines is recommended.

Abstract PR05: Utilizing electronic fertility clinic records and registry linkage to establish a retrospective population-based cohort study to evaluate the association between in vitro fertilization (IVF) and subsequent cancer risk in women

Abstract Background: Since the introduction of in vitro fertilization (IVF) in 1978, the use of assisted reproduction technology (ART) has increased annually with an estimated 240,000 ART-conceived children born each year worldwide. Despite its widespread use, the impact on subsequent maternal and child health is not well understood. Specifically, cancer risk in women receiving IVF treatment has not been adequately evaluated, in part due to the complex nature of the research question and the need for large numbers of exposed women with long follow-up to evaluate rare cancer outcomes. Methods: To address this research question, we designed a country-wide retrospective medical record linkage study that utilizes electronic records from all IVF units in operation in Israel between 1997 and 2014. Linkage to cancer registry is facilitated via unique national identification numbers. We selected Israel for this study because it has the highest rate of ART/IVF exposure in the world, with 24 IVF units in the country that perform more than 45,000 ART cycles annually. Fertility treatment is fully covered by national health insurance with no restriction on the number of cycles or type of procedure, thus reducing potential selection issues related to access to care that may exist in other populations. We are currently collecting medically documented and detailed exposure information from the IVF units, including causes of infertility, hormonal treatments, procedures (e.g., IVF), and important covariates (e.g., parity, body mass index, etc.). To date we have collected exposure and covariate information from 18,470 women receiving treatment at 9 IVF clinics and conducted an interim linkage with the cancer registry through December 2014, providing on average 15 years of follow-up. We calculated standardized incidence ratios (SIRs) for all cancers combined and separately for breast cancer and further evaluated breast cancer risk with number of treatment cycles using Cox proportional hazards regression. Results: Based on interim registry linkage we identified 611 invasive cancers including 272 breast cancers among 18,470 women with more than 236,000 woman-years of follow-up. The incidence of cancer [SIR (95% confidence interval (CI)): 0.96 (0.88-1.04)] or breast cancer [0.98 (0.87-1.11)] was not elevated compared to the general population. Further, breast cancer risk was not associated with increased number of IVF treatment cycles [adjusted hazard rate ratio (RR) (95% CI) per IVF cycle: 1.01 (0.96-1.09)]. Conclusions: With this data we have demonstrated the feasibility of linking IVF clinic data with the nationwide cancer registry to evaluate cancer risk. In our preliminary analyses, IVF treatment was not associated with risk of incident invasive cancer or breast cancer. Given that continued linkage with the cancer registry is feasible, we will be able to monitor long-term cancer risks associated with IVF treatment using the enumerated data. This abstract is also being presented as Poster A15. Citation Format: Britton Trabert, Galit Hirsh-Yechezkel, Adel Farhi, Inna Zaslavsky, Shai E. Elizur, Arik Kahana, Raoul Orvieto, Hananel Holzer, Ilan Calderon, Shevach Friedler, Einat Shalom-Paz, Raphael Ron-El, Arie Raziel, Louise A. Brinton, Liat Lerner-Geva. Utilizing electronic fertility clinic records and registry linkage to establish a retrospective population-based cohort study to evaluate the association between in vitro fertilization (IVF) and subsequent cancer risk in women [abstract]. In: Proceedings of the AACR Special Conference on Modernizing Population Sciences in the Digital Age; 2019 Feb 19-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(9 Suppl):Abstract nr PR05.

Randomized study of G-TL and global media for blastocyst culture in the EmbryoScope: morphokinetics, pregnancy, and live births after single-embryo transfer

To evaluate the efficacy of two different invitro fertilization culture media for blastocyst development, pregnancy, and live birth rate. Global (GB) medium (used without refreshment) and G-TL medium (designed specifically for culture in time-lapse incubators) were compared. Prospective randomized study of sibling embryo culture in two culture media. Invitro fertilization clinic. Women undergoing fresh or frozen cycles using autologous or donor oocytes. None. The primary endpoints were implantation, pregnancy, and live birth rate (LBR) after single blastocyst transfer. Secondary endpoints included embryo morphokinetics, development of good-quality blastocysts, and euploidy rate. Kinetic data from 10,768 sibling pronucleate embryos cultured in the EmbryoScope were compared. GB embryos initiated compaction earlier and formed morula sooner than their G-TL counterparts. The mean timing for start of blastulation did not differ. The interval between start of blastulation and time of blastocyst formation was observed to be <12 hours for proportionately more GB compared with G-TL-cultured embryos. Despite a higher rate of observed dysmorphisms in GB embryos, the euploidy rate among biopsied blastocysts did not differ between media. A total of 820 single-embryo transfer cycles were performed. Implantation rates were similar between media, independent of whether the embryo transferred was fresh (GB 58.7% vs. G-TL 61.7%) or frozen (GB 64.1% vs. G-TL 60.5%). Live birth rates were also not different. With GB medium, the LBR for fresh and frozen transfers was 54.2% and 53.1%, respectively, as compared with 51.1% and 50%, respectively, with G-TL. Uninterrupted culture in a time-lapse incubator without medium refreshment was well supported by both media tested. Differences in morphokinetics did not necessarily dictate the superiority of one media over the other. Both pregnancy and LBR were not significantly influenced by choice of culture medium. The euploidy rate was also independent of culture medium.

First effective mHealth nutrition and lifestyle coaching program for subfertile couples undergoing in vitro fertilization treatment: a single-blinded multicenter randomized controlled trial

To study compliance and effectiveness of the mHealth nutrition and lifestyle coaching program Smarter Pregnancy in couples undergoing invitro fertilization (IVF) treatment with or without intracytoplasmic sperm injection (ICSI). Multicenter, single-blinded, randomized controlled trial, conducted from July 2014 to March2017. IVF clinics. A total of 626 women undergoing IVF treatment with or without ICSI and 222 male partners. Couples were randomly assigned to the light (control group) or regular (intervention group) Smarter Pregnancy program. Both groups filled out a baseline screening questionnaire on nutrition and lifestyle behaviors, and the intervention group received coaching tailored to inadequate behaviors during the 24-week period. Difference in improvement of a composite dietary and lifestyle risk score for the intake of vegetables, fruits, folic acid supplements, smoking, and alcohol use after 24 weeks of the program. Compared with control subjects, women and men in the intervention group showed a significantly larger improvement of inadequate nutrition behaviors after 24 weeks of coaching. At the same time, the women also showed a significantly larger improvement of inadequate lifestyle behaviors. The mHealth coaching program Smarter Pregnancy is effective and improves the most important nutritional and lifestyle behaviors among couples undergoing IVF/ICSI treatment. International multicenter randomized trials are recommended to study the effect of using Smarter Pregnancy on pregnancy, live birth, and neonatal outcome. NTR4150.

Per- and poly-fluoroalkyl substances (PFASs) in follicular fluid from women experiencing infertility in Australia

Per- and poly-fluoroalkyl substances (PFASs) have been widely used and detected in human matrices. Evidence that PFAS exposure may be associated with adverse human reproductive health effects exists, however, data is limited. The use of a human matrix such as follicular fluid to determine chemical exposure, along with reproductive data will be used to investigate if there is a relationship between PFAS exposure and human fertility. ObjectiveThis study aims to: (1) assess if associations exist between PFAS concentrations and/or age and fertilisation rate (as determined in follicular fluid of women in Australia who received assisted reproductive treatment (ART)); and (2) assess if associations exist between PFAS concentrations and infertility aetiology. MethodsFollicular fluids were originally collected from participants who underwent fully stimulated ART treatment cycles at an in vitro fertilisation (IVF) clinic in the period 2006–2009 and 2010–11 in Queensland, Australia. The samples were available for analysis of 32 PFASs including perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonate (PFHxS), and perfluorononanoic acid (PFNA) using high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). 97 samples were matched with limited demographic data (age and fertilisation rate) and five infertility factors (three known female factors): 1) endometriosis, 2) polycystic ovarian syndrome (PCOS), and 3) genital tract infections - tubal/pelvic inflammation disease; as well as 4) male factor, and 5) idiopathic or unknown from either males or females. SPSS was used for linear regression analysis. ResultsPFASs were detected in all follicular fluid samples with the mean concentrations of PFOS and PFOA, 4.9, and 2.4 ng/ml, respectively. A lower fertilisation rate was observed at higher age when age was added as a covariate, but there was no relationship between PFAS concentrations and fertilisation rate. There were few statistically significant associations between PFAS concentrations in follicular fluid and infertility factors. Log-transformed PFHxS concentrations were lower in females with endometriosis (factor 1) than in women who had reported ‘male factors’ as a reason of infertility, while PFHpA was higher in women who had infertile due to female factors (factor 1–3) compared to those who had infertile due to male factor. ConclusionPFASs were detected in follicular fluid of Australian women who had been treated at an IVF clinic. PFAS exposure found in follicular fluids is linked to increased risk of some infertility factors, and increased age was associated with decreased fertilisation rate in our data. But there was no relationship between PFAS and ferlitisation rate. Further large-scale investigations of PFAS and health effects including infertility are warranted.

Endometriosis screening in patients attending an IVF clinic: a proof-of-concept retrospective cohort study

Given that (i) endometriosis affects approximately 40% of women diagnosed with fertility problems and (ii) this condition may be an underestimated cause of idiopathic infertility, it is essential to identify high-risk patients for laparoscopic screening and reduce the diagnostic delay. We performed a retrospective analysis of 312 women (208 diagnosed with endometriosis and 104 controls) admitted to an in vitro fertilisation (IVF) unit in the city of Brest (France) between June 2007 and July 2014. As part of the women’s infertility treatment, levels of cancer antigen 125 (CA-125) were assayed in blood samples collected on the day of oocyte retrieval. Surplus serum was used to set up a new sperm agglutination test. It was observed that sperm agglutination was significantly correlated with endometriosis and CA-125 levels (p < 0.01 for both). By building a decision tree, we identified a subpopulation of patients with low CA-125 levels and a high risk of endometriosis. This proof-of-concept study constitutes a first step towards a high-quality, controlled, multi-centre trial. If our preliminary results are confirmed, the decision tree should improve the medical care given to women in IVF programmes by identifying potential endometriosis sufferers for laparoscopic examination and enabling them to be counselled about precautionary measures.

Double trouble? Clinic-specific risk factors for monozygotic twinning

To investigate clinic-specific risk factors for monozygotic twinning (MZT) using a large, electronic database. Retrospective case-control study. Infertility clinics. Using an electronic medical record system, viable clinical pregnancy (confirmation of a gestational sac(s) and presence of at least one fetal pole with a heartbeat on first trimester ultrasound), data were obtained from homologous invitro fertilization (IVF) cycles after single ET from June 1, 2004, to December 31, 2016. Monozygotic twinning was defined as a pregnancy with two fetal heartbeats on ultrasound with sex concordance at birth. None. Risk factors for MZT including cycle type, method of insemination, and method of cryopreservation. Of the 28,265 IVF cycles that met inclusion criteria over the study period, 8,749 (31.0%) resulted in a viable intrauterine clinical pregnancy. There were 102 (2.7%) MZT in the fresh cycle cohort and 133 (2.7%) in the frozen cycle cohort. Neither cryopreservation nor the method of cryopreservation was a significant risk factor for MZT. However, the use of sequential media was an independent risk factor for MZT in fresh, but not frozen, ETs (odds ratio = 1.72, 95% confidence interval, 1.10-2.68). Significant differences were seen in the incidence of MZT between clinics, and this difference persisted after controlling for known risk factors (clinic 0, reference; clinic 2, odds ratio = 2.22; 95% confidence interval, 1.48-3.32; clinic 3, odds ratio = 1.93; 95% confidence interval, 1.30-2.87). Differences in MZT rates exist between individual IVF clinics, suggesting that variations in practice patterns may contribute to this event. The present study noted the use of sequential media was an independent risk factor for fresh but not frozen cycles.

Why is use of donor eggs not viewed as treatment failure? A call for improvements in treatments with autologous oocytes

Based on national registry reports, after age 42, the number of IVF cycles utilizing autologous oocytes is very small; after age 43, autologous oocyte use in US IVF cycles is almost non-existent. We here argue that the in vitro fertilization (IVF) field has created a self-fulfilling prophecy by basically abandoning the utilization of autologous oocytes after ages 42-43years. This not only resulted in almost no IVF cycles with autologous oocytes being performed but also in abandonment of research that could lead to improvements in IVF outcomes in older women when using autologous oocytes. As a consequence, IVF has largely stagnated in this area. We further argue that third-party oocyte donation in clinical IVF should be considered a treatment failure, as it requires patients to choose a second rather than a first-choice treatment. Such a redesignation of third-party egg donation would not only be appropriate but could lead to necessary changes in physician attitudes, considering that women almost exclusively prefer to conceive with their autologous oocytes.

Cumulative Live Birth Rates According to Maternal Body Mass Index After First Ovarian Stimulation for in vitro Fertilization: A Single Center Analysis of 14,782 Patients.

Objective: To investigate the cumulative live birth rates (CLBR) according to body mass index (BMI) in women undergoing their first in vitro fertilization (IVF).Design: Retrospective cohort analysis.Setting: An IVF clinic in a public hospital.Patients: This is a retrospective study of 14,782 patients undergoing their first fresh IVF cycles and subsequent frozen embryo transfers in our clinic from January 2014 to January 2017. The follow-up for CLBR continued until January 2019. Patients with a BMI <18.5 kg/m2 were considered to be underweight and those with a BMI > 24 kg/m2 were considered to be overweight. Patients with a BMI ≥ 28 kg/m2 were considered to be obese.Intervention(s): None.Primary Outcome Measure: The primary outcome was cumulative live birth rate (CLBR).Result(s): This study illustrated the “inverted U shape” associations between body weight and IVF outcome (CLBR). The turning points in threshold analysis, as found by an automatic search, were BMIs of 18.5 and 30.4 kg/m2. The main finding of this retrospective data analysis is that the CLBR increased in underweight women, plateaued for normal weight and overweight women with a BMI between 18.5 and 30.4 kg/m2, and decreased in obese women.Conclusion(s): The data suggested an “inverted U shape” association between BMI and CLBR. The CLBR increases in underweight women, plateaus in normal weight and overweight women, and then decreases in obese women.

Preimplantation genetic testing for aneuploidy (PGT-A)-finally revealed.

Natural fecundity of women decreases gradually and more rapidly after age 37 years. This decrease is accompanied by rising aneuploidy rates of pregnancies and can also be observed in products of conception of spontaneous abortions [1]. These observations lead to the hypothesis that transferring only euploid embryos in association with in vitro fertilization (IVF) might decrease miscarriages and increase live birth rates (LBRs), attesting-procedure now called preimplantation genetic testing (of embryos) for aneuploidy (PGT-A), until recently generally referred to as preimplantation genetic screening (PGS). Verlinsky and Kuliev further proposed that the removal of all aneuploid embryos prior to transfer would improve implantation rates and live birth rates and suggested that the diagnosis be made via biopsy of both polar bodies [2]. Polar body biopsy, however, proved technically too difficult for general IVF practice and would have revealed only meiotic aneuploidies. The procedure was, therefore, initially performed biopsying 1–2 blastomeres of day-3 cleavage-stage embryos, often given the acronym PGS 1.0. This form of embryo testing has, since, been replaced by PGS 2.0, with the embryo biopsy being moved from day-3 cleavage stage to trophectoderm biopsy of blastocyst-stage embryos on days 5–6 after fertilization. In July 2016, another major change in PGT-A was announced, for the first time introducing the concept pf “mosaic” embryos (also called PGS 3.) (Preimplantation Genetic Diagnosis Society (PGDIS) position statement on chromosome mosaicism and preimplantation aneuploidy testing at the blastocyst stage, Chicago, IL; July 19, 2016 http://pgdis.org/docs/newsletter_071816.html). After almost two decades of PGS 1.0 through PGS 3.0, the procedure has, however, still been unable to demonstrate the promised improvements in live births and anticipated declines in miscarriage rates [3–5]. Several studies, even summarized in a meta-analysis [6], have claimed improved clinical IVF outcomes following PGT-A. They, however, reported IVF outcomes with reference point embryo transfer rather than cycle start (intent-to-treat) and, therefore, by excluding poorer prognosis patients, were severely biased [7]. The STAR study This is why the recently published STAR study [8] attracted special attention: It avoided at least some patient selection biases of earlier fresh-cycle studies by being prospectively randomized and reporting on IVF outcomes from transfers of only single frozen-thawed embryos at blastocyst stage. That qualifying patients required having at least two frozen embryos from a prior fresh cycle, however, still demonstrates a favorable patient selection bias. Importantly, however, the study at least analyzed outcomes for study and control groups with reference point initial first cycle start [7]. In doing so, the study convincingly revealed no improvements in live birth rates and no reduction in miscarriage rates when cycle outcomes were compared in singe-embryo transfers at blastocyst stage between women, randomized to either PGT-A or only morphological assessments of a single embryo prior to transfers [8]. For no declared reason, the authors then, however, performed a post hoc sub-group analysis based on age and reported, between ages 35 and 40 years, that PGT-A, still, offered significant increases in ongoing pregnancy rate (OPR). In the discussion of their manuscript, they emphasized this finding as “continuous evidence” for the clinical utility of PGT-A in at least that age group. Again, in contrast to the overall study that had been performed with reference point cycle start (intent-to-treat), their post hoc analysis was performed with reference embryo transfer and, therefore, statistically suspect. Because results of the STAR study are already impacting IVF practice worldwide, we here offer a statistically corrected analysis of the STAR study, reaffirming the study’s overall findings by refuting the results of the post hoc analysis and its interpretation by the authors, claimed benefits for PGT-A utilization for all age groups.

Blastocyst elective single embryo transfer improves perinatal outcomes among women undergoing assisted reproductive technology in Indonesia

Objective: To compare the effectiveness of blastocyst elective single embryo transfer (eSET) and double embryo transfer (DET) in reducing low birth weight, preterm birth, and perinatal mortality in in vitro fertilization (IVF) cycles of Indonesian women.Methods: A retrospective observational study was conducted at Morula IVF Clinic, Jakarta, Indonesia. A total of 179 women who underwent either eSET or DET and had met the eligibility criteria were included. Seventy-six women underwent eSET while 103 underwent DET in their IVF cycles. Low birth-weight rate, preterm birth rate, and perinatal mortality rate of both groups were measured as the primary study outcomes. Neonatal intensive care unit (NICU) admission rate, Apgar score, multiple pregnancy, and maternal complications during pregnancy were also evaluated.Results: The risk of low birth weight [odds ratio (OR)=0.21, 95% confidential interval (CI): 0.10-0.45, P<0.001] and preterm birth (0R=0.25, 95% CI: 0.13-0.49, P<0.001) was significantly lower in the eSET group compared with the DET group. Furthermore, eSET efficiently reduced the incidence of NICU admission and multiple pregnancy (P=0.01 and P<0.001, respectively). No significant difference was observed in terms of perinatal mortality rate, Apgar score, and maternal complications including gestational diabetes, preeclampsia as well as pregnancy-induced hypertension (P>0.05). However, a lower incidence of antepartum hemorrhage was noticed in the eSET group than in the DET group (P=0.03).Conclusions: Compared with DET, infants conceived through IVF cycles with eSET have a significantly lower risk of low birth weight, preterm birth, and NICU admissions. Moreover, eSET is shown to reduce multiple pregnancy rate, yet no significant differences are observed in the perinatal mortality rates, Apgar score and maternal complications (except for the incidence of antepartum hemorrhage) between both groups.

Sperm selection in IVF: the long and winding road from bench to bedside.

Spermatozoa wage battle to conquer fertilization but the traits needed to succeed remain elusive. The natural advantageous qualities that enable only a few selected sperm cells to reach the site of fertilization remain unknown. Although in vitro fertilization (IVF) facilitates the job of spermatozoa, a universally acceptable means of sperm selection is yet to be developed. No objective or reliable sperm quality indicators have been established and sperm selection is, to a great extent, based on subjective qualitative evaluation. The best method for sperm selection in IVF presents several challenges: intrinsic sperm qualities cannot be evaluated and the ideal endpoint for these studies is debatable. An ideal method for sperm selection in ART should be noninvasive and cost-effective, and allow the identification of high-quality spermatozoa and yield better outcomes in terms of pregnancy and live birth rates. This narrative review included 85 papers and focused on the new available methods and technologies that might shed some light on sperm selection in IVF. It discusses the available data on microfluidic devices, omics profiling, micronuclei studies, sperm plasma membrane markers, and other techniques, such as Magnetic Activated Cell Sorting (MACS), Raman micro-spectroscopy, and artificial intelligence systems. The new techniques herein reviewed offer fresh approaches to an old problem, for which a definite solution has yet to cross the bridge from bench to IVF clinics around the world, since clinical usefulness and application remain unproven.

Depression and Anxiety Disorders amongst a Cohort of Infertile Women Attending an In-Vitro Fertilization Clinic in South-western Nigeria

Background: Psychological consequences of infertility have been documented in both developed and less developed countries. Depression and anxiety disorders have been identified as important causative factors. The prevalence of psychiatric morbidity amongst infertile women has been shown to be quite high with values as high as 46.4%. A high premium is placed on childbirth in Nigeria and failure to conceive is associated with disastrous consequences. Failed In-Vitro Fertilization (IVF) cycles have been implicated in psychological distress.&#x0D; Objective: This study aimed to determine the prevalence of anxiety and depression amongst infertile women undergoing IVF and to examine the psychosocial stressors associated with the development of these morbidities.&#x0D; Materials and Methods: A descriptive crosssectional study of fifty-one infertile women attending an In-Vitro Fertilization clinic in Lagos, South Western, Nigeria. Participants were recruited consecutively at their first consultation visit and a self-administered questionnaire consisting of sociodemographic information along with the Hospital Anxiety and Depression Scale (HADS) was completed by the participants. Data obtained from the respondents was analyzed using the Statistical Package for Social Sciences (IBM SPSS, New York) version 21. The Chi-Square statistic was used in testing for associations between categorical variables.&#x0D; Results: The mean age of the respondents was 38.96 ± 5.91 years with a range of 23-49 years. 76.5% (39/51) of the women had infertility greater than 5 years, while 49 % (25/51) of the women were aged 40 years and above with 96% (24/25) of this group experiencing infertility greater than 5 years. Anxiety was recorded in 24 respondents (47.1%) while Eighteen respondents (35.3%) had evidence of depression. Marital disharmony was found to be associated with the development of anxiety (P&lt;0.05).&#x0D; Conclusion: The impact of infertility on the Nigerian couple can be devastating. Lack of support coupled with the overbearing and intrusive nature of family members predisposes to the development of psychosocial distress. We therefore recommend that Physicians pay attention to the psychosocial stressors experienced by infertile women prior to In-Vitro Fertilization with the aim of ensuring appropriate referral for psychiatric assessment and treatment.

Preliminary assessment of aneuploidy rates between the polar, mid and mural trophectoderm.

The objective of this study is to compare aneuploidy rates between three distinct areas of the human trophectoderm: mural, polar and a region in between these two locations termed the 'mid' trophectoderm. This is a cohort study on in vitro fertilization (IVF) patients undergoing comprehensive chromosome screening at the blastocyst stage at a private IVF clinic. All embryos underwent assisted hatching on day 3 with blastocyst biopsy and comprehensive chromosome screening. Biopsied blastocysts were divided into three groups depending on which area (polar, mid, or mural) of the trophectoderm was protruding from the zona pellucida and biopsied. Aneuploidy rates were significantly higher with cells from the polar region of the trophectoderm (56.2%) compared with cells removed from the mural region of the trophectoderm (30.0%; P = 0.0243). A comparison of all three areas combined also showed a decreasing trend, but this did not reach clinical significance, polar (56.2%), mid (47.4%) and mural trophectoderm (30.0%; P = 0.1859). The non-concordance demonstrated between polar and mural trophectoderm can be attributed to biological occurrences including chromosomal mosaicism or procedural differences between embryologists.

The Affordability and Accessibility of Ontario's Publicly Funded IVF Program: A Survey of Patients

On December 21, 2015, the Province of Ontario created the Ontario Fertility Program to fund one cycle of in vitro fertilization (IVF) to improve IVF affordability and access for Ontarians below age 43. The objective of this study was to determine whether the Program was meeting this goal, based on the experiences of participating patients. Participation in an electronic survey was invited through posters and brochures placed within the waiting rooms of all 25 IVF clinics providing funded IVF in Ontario and by a survey link placed on websites focused on fertility issues. The survey was carried out at the end of the second year of the Program (September to December 2017), with 514 participants completing >75% of it. Program strengths were noted as follows: decreases in financial inequities of family building for the infertile; lowering of the opportunity cost of accessing IVF; and destigmatizing and raising public awareness of infertility as a legitimate medical condition. Weaknesses were as follows: lack transparency and consistency in clinics' patient prioritization schemes; clinic concentration in cities leading to geographic inequities in access; and high ancillary costs being financially burdensome. The following opportunities were suggested: funding of more than one IVF cycle and its supporting medications; standardization of prioritization schemes; and tying Program access to means testing. Patients strongly support the Program and noted improved IVF affordability, but the Program's reliance on existing private clinics for treatment provision has meant unresolved geographic inequities and inconsistent prioritization schemes. Because this is the first Program study of patients' experience, the results will help policymakers determine areas to re-evaluate for continued or increased funding and opportunities to collaborate with health care providers and clinic owners to improve provision and access.

Oocyte meiotic spindle morphology is a predictive marker of blastocyst ploidy—a prospective cohort study

To evaluate oocyte meiotic spindle (OMS) morphology at intracytoplasmic sperm injection (ICSI) as a predictor of blastocyst ploidy and whether OMS morphology could aid standard morphology-based blastocyst selection. Prospective cohort study. Invitro fertilization clinic. Patients undergoing ICSI cycles with an intention to perform preimplantation genetic testing for aneuploidy (PGT-A) from October 2014 to December2017. The OMS was visualized with the use of polarized light microscopy at the time of ICSI and the morphology classified as normal, dysmorphic, translucent, not visible, or in telophase. Blastocyst biopsy for PGT-A was performed on embryos with suitable development. The association of OMS morphology with the resulting blastocyst ploidy was evaluated on an "intention-to-treat" (ITT) and an "as-treated analysis" (ATA) basis. The morphology of 2,056 OMSs were classified. A strong association of OMS morphology with fertilization, cleavage to at least 6cells on day 3, and good/top-quality blastocyst formation was present. Normal OMS was positively associated with blastocyst euploidy compared with all other OMS types combined, per either ITT or ATA. Even after controlling for female age, blastocyst quality, and developmental stage, the presence of a normal OMS was strongly associated with the probability of blastocyst euploidy. OMS morphology is a predictive marker of blastocyst ploidy and can potentially aid standard morphology-based blastocyst selection.

Identification of Novel Microsatellite Markers Flanking the SMN1 and SMN2 Duplicated Region and Inclusion Into a Single-Tube Tridecaplex Panel for Haplotype-Based Preimplantation Genetic Testing of Spinal Muscular Atrophy.

Preimplantation genetic testing for the monogenic disorder (PGT-M) spinal muscular atrophy (SMA) is significantly improved by supplementation of SMN1 deletion detection with marker-based linkage analysis. To expand the availability of informative markers for PGT-M of SMA, we identified novel non-duplicated and highly polymorphic microsatellite markers closely flanking the SMN1 and SMN2 duplicated region. Six of the novel markers within 0.5 Mb of the 1.7 Mb duplicated region containing SMN1 and SMN2 (SMA6863, SMA6873, SMA6877, SMA7093, SMA7115, and SMA7120) and seven established markers (D5S1417, D5S1413, D5S1370, D5S1408, D5S610, D5S1999, and D5S637), all with predicted high heterozygosity values, were selected and optimized in a tridecaplex PCR panel, and their polymorphism indices were determined in two populations. Observed marker heterozygosities in the Chinese and Caucasian populations ranged from 0.54 to 0.86, and 98.4% of genotyped individuals (185 of 188) were heterozygous for ≥2 markers on either side of SMN1. The marker panel was evaluated for disease haplotype phasing using single cells from two parent–child trios after whole-genome amplification, and applied to a clinical IVF (in vitro fertilization) PGT-M cycle in an at-risk couple, in parallel with SMN1 deletion detection. Both direct and indirect test methods determined that none of five tested embryos were at risk for SMA, with haplotype analysis further identifying one embryo as unaffected and four as carriers. Fresh transfer of the unaffected embryo did not lead to implantation, but subsequent frozen-thaw transfer of a carrier embryo produced a pregnancy, with fetal genotype confirmed by amniocentesis, and a live birth at term.

Noninvasive embryo selection: kinetic analysis of female and male pronuclear development to predict embryo quality and potential to produce live birth

To evaluate a noninvasive method of examining euploid embryos, focusing on kinetic analyses, from second polar body extrusion to pronuclear membrane breakdown (PNMBD). Retrospective embryo cohort study. Private IVF clinic. 213 frozen-thawed single blastocyst transfers. Fertilized oocytes were recorded by means of time-lapse photography, followed by kinetic analysis of female and male pronuclei (PNs). The differences in size between the 2PNs in embryos resulting in live births compared with those of embryos from failed pregnancies were analyzed according to sequential size from early PN stages to PNMBD. It was found that the difference in areas between male and female PNs immediately before PNMBD is a better predictor of embryo quality if this difference is below a known cutoff value. The size of male PNs 8hours before the onset of PNMBD should be larger than female PNs (B). The difference in size between male and female PNs 8hours before PNMBD should be larger than the difference in their size immediately before PNMBD. When normal embryos were defined using the equation (A∪C)∩B, the birth rates for invitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) were 68.1% and 50.0%, respectively. For the remaining embryos, defined as abnormal according to the above criteria, birth rates were 9.4% for IVF and 4.2% for ICSI. We have developed a method for noninvasive embryo evaluation by means of the kinetic analysis of female and male PN growths. This method should enable us to select embryos that have a higher potential for healthy births.