Assisted Reproductive Technology Success Research Articles

Artificial intelligence model utilizing endometrial analysis to contribute as a predictor of assisted reproductive technology success

This study addresses the development of EndoClassify, an artificial intelligence (AI) model designed to assess endometrial characteristics and enhance embryo receptivity. Utilizing a dataset of 402 endometrial ultrasound images augmented to 14.989, EndoClassify, incorporating Attention U-Net for image segmentation and GoogLeNet Inception for image classification, demonstrated exceptional performance with an accuracy of 95%, loss of 10%, a sensitivity of 93%, and specificity of 93%. The significance of EndoClassify extends beyond its robust metrics. This AI model has transformative potential in clinical settings, offering specialists a reliable, rapid, and accurate tool for endometrial assessment in assisted reproduction technology (ART) cycles. Identifying ‘good endometrium’ with 71% accuracy, corresponding to a 74% pregnancy rate, underscores EndoClassify’s role in significantly improving patient outcomes. In conclusion, the seamless integration of ultrasonographic parameters and AI techniques enhances efficiency in clinical decision-making and signifies a crucial collaboration between advanced technology and clinical expertise. While acknowledging the retrospective design as a limitation, it is imperative to highlight potential biases introduced by this design. Additionally, including fresh and frozen embryo transfers without known ploidy status adds transparency to the study’s limitations. EndoClassify stands as a beacon of progress, poised to revolutionize personalized treatment strategies and bring tangible benefits to specialists and patients in the dynamic landscape of assisted reproductive technology.

A scoping review of infertility research conducted in the Republic Of Ireland

Background Approximately 25 million citizens in Europe experience infertility. Until September 2023, the Republic of Ireland (RoI) was the only state in the European Union that did not offer any state-funded access to Assisted Reproductive Technology (ART). As research supports the understanding, and improvement, of care delivery, and research activity is associated with healthcare performance, it seems timely to develop an understanding of infertility research to-date in RoI. The aim of this scoping review was to examine the extent and nature of research on infertility conducted in RoI. Methods A protocol for this scoping review was published through the Open Science Framework (https://doi.org/10.17605/OSF.IO/H8F4Y) in March 2023. The search strategy was comprised of electronic searches, review of reference lists, grey literature searches, and screening of publications from the European Society of Human Reproduction and Embryology and the International Committee for Monitoring Assisted Reproductive Technologies. Studies focused on infertility or infertility care that were conducted in RoI were included. Deductive content analysis was used to cluster studies. Results In total, 105 studies were included and published between 1951 and 2023, with a marked increase from 2010. Studies most frequently considered Success Rates of ART (31.4%), Service Description and Evaluation (12.4%), and Optimising Treatment Regimes or Protocols (11.4%). Conclusions The sizable body of research is congruent with the increasing burden of infertility. However, the literature is limited by a predominant focus on ART success rates, a dearth of qualitative studies, limited engagement with healthcare providers, and limited exploration of the quality of care provision. This review may offer a useful model for researchers in other countries. The variability in availability, and outcomes, of ART across Europe conveys the necessity of understanding and advancing research within individual countries and health systems as well as internationally.

Prediction of embryo euploidy and pregnancy outcome by blastocyst morphology and development speed for women receiving single embryo transfer

Background Selection of high-quality blastocysts is the most important factor determining the success of assisted reproductive technology. The objective of this study is to assess the values of blastocyst morphological quality and development speed for predicting euploidy and clinical pregnancy outcome. Methods A total of 155 preimplantation genetic testing cycles including 959 blastocysts and 154 euploid blastocyst transfer cycles conducted between January 2018 and December 2019 were retrospectively analysed. The associations of blastocyst morphological quality and development speed (D) with chromosomal status, clinical pregnancy rate, early miscarriage rate, and ongoing pregnancy rate were evaluated by univariate and multivariate regression. Results The euploidy rate of development speed D5 blastocysts was significantly greater than that of D6 blastocysts (61.4% vs. 38.1%, P < 0.001), and the euploid rate of morphologically high-grade blastocysts was significantly greater than that of non-high-grade blastocysts. Development speed D5 (OR = 1.6, 95% CI 1.2–2.2, P = 0.02) and high-grade morphology (OR = 2.1, 95% CI 1.5–2.9, P = 0.01) were independent predictors of euploidy. The ongoing pregnancy rate of D5 blastocysts was significantly higher than that of D6 blastocysts (62.3% vs. 43.8%, P = 0.04). Transfer of euploid blastocysts with high-grade morphology resulted in a greater ongoing pregnancy rate than transfer of non-high-grade euploid blastocysts (60.7% vs. 43.2%, P = 0.049). Alternatively, D6 development speed was an independent risk factor for early pregnancy loss after euploid blastocyst transfer. Multivariate regression analysis adjusting for confounding factors identified maternal age, blastocyst development speed, and blastocyst morphological grade as independent predictors of euploidy but not of clinical pregnancy. Conclusion The recommended sequence of embryo transfer based on the present study is D5 high-grade > D6 high-grade > D5 non-high-grade > D6 non-high-grade.

Poor ovarian response classification systems in the clinical setting - time for an update?

Poor ovarian response (POR) remains a key challenge to the success of assisted reproductive technology. Here, we offer a comprehensive review of the two main classification systems for POR, discussing their promises and pitfalls, evaluating their performance, and exploring potential avenues for improving upon these definitions of POR. The Bologna criteria represented the first meaningful attempt to create a universal POR definition. Subsequently, the POSEIDON classification system was published to provide a more nuanced view of POR, classifying patients into four groups based on age and ovarian reserve markers. A recent study evaluated the likelihood of achieving at least one euploid embryo for transfer and found that, indeed, these classification systems are effective predictors of this outcome.While these criteria provide an effective counseling tool, several limitations - not considering underlying conditions, selecting somewhat arbitrary cutoffs, and evaluating the number of oocytes retrieved regardless of maturity - highlight the importance of improving upon these systems to create a more useful tool to more accurately predict ovarian response for clinical and research purposes. In the era of personalized medicine, it is time to reconsider whether diagnostic criteria for a continuous metric such as ovarian response should be based on meeting all-or-nothing thresholds for specific parameters.

Current understanding of the pathogenesis of placenta accreta spectrum disorder with focus on mitochondrial function.

The refinement of assisted reproductive technology, including the development of cryopreservation techniques (vitrification) and ovarian stimulation protocols, makes frozen embryo transfer (FET) an alternative to fresh ET and has contributed to the success of assisted reproductive technology. Compared with fresh ET cycles, FET cycles were associated with better in vitro fertilization outcomes; however, the occurrence of pregnancy-induced hypertension, preeclampsia, and placenta accreta spectrum (PAS) was higher in FET cycles. PAS has been increasing steadily in incidence as a life-threatening condition along with cesarean rates worldwide. In this review, we summarize the current understanding of the pathogenesis of PAS and discuss future research directions. A literature search was performed in the PubMed and Google Scholar databases. Risk factors associated with PAS incidence include a primary defect of the decidua basalis or scar dehiscence, aberrant vascular remodeling, and abnormally invasive trophoblasts, or a combination thereof. Freezing, thawing, and hormone replacement manipulations have been shown to affect multiple cellular pathways, including cell proliferation, invasion, epithelial-to-mesenchymal transition (EMT), and mitochondrial function. Molecules involved in abnormal migration and EMT of extravillous trophoblast cells are beginning to be identified in PAS placentas. Many of these molecules were also found to be involved in mitochondrial biogenesis and dynamics. The etiology of PAS may be a multifactorial genesis with intrinsic predisposition (e.g., placental abnormalities) and certain environmental factors (e.g., defective decidua) as triggers for its development. A distinctive feature of this review is its focus on the potential factors linking mitochondrial function to PAS development.

Legal and ethical challenges in assisted reproductive technology practice in Ghana

Objective: Infertility remains a global challenge, with assisted reproductive technology (ART) progressively gaining relevance in developing countries, including Ghana. However, associated ethico-legal challenges have not received the needed policy attention. This study explored the legal and ethical challenges of ART practice in Ghana.Design: The study employed an exploratory phenomenological approach to examine ART in Ghana, focusing on ethics and law governing this practice.Participants: Respondents were ART practitioners, managers, facility owners, representatives of surrogacy/gamete donor agencies, and regulatory body representatives.Methods: A semi-structured interview guide was used to collect data. The in-depth interviews were audiotaped, and responses transcribed for analysis through coding, followed by generation of themes and sub-themes, supported with direct quotes.Results: It emerged that there are no ethical and legal frameworks for ART practice in Ghana, and this adversely affects ART practice. Ethical challenges identified border on informed consent, clients’ privacy and clinical data protection, gamete donation issues, multiple gestations, single parenting, and social and religious issues. The legal challenges identified include the non-existence of a legal regime for regulating ART practice and the absence of a professional body with clear-cut guidelines on ART practice. In the absence of legal and ethical frameworks in Ghana, practitioners intimated they do comply with internationally accepted principles and general ethics in medical practice.Conclusion: There are no regulations on ART in Ghana. Legal and ethical guidelines are essential to the provision ofsafe and successful ART practices to protect providers and users. Governmental efforts to regulate Ghana need to beprioritized.

Outpatient hysteroscopy impact on subsequent assisted reproductive technology: a systematic review and meta-analysis in patients with normal transvaginal sonography or hysterosalpingography images

BackgroundStandard management for intrauterine lesions typically involves initial imaging followed by operative hysteroscopy for suspicious findings. However, the efficacy of routine outpatient hysteroscopy in women undergoing assisted reproductive technology (ART) remains uncertain due to a lack of decisive high-quality evidence. This study aimed to determine whether outpatient hysteroscopy is beneficial for infertile women who have unremarkable imaging results prior to undergoing ART.MethodsA systematic review and meta-analysis were conducted following PRISMA guidelines, incorporating data up to May 31, 2023, from databases such as PubMed, Embase, and the Cochrane Library. The primary outcome assessed was the live birth rate, with secondary outcomes including chemical pregnancy, clinical pregnancy rates, and miscarriage rates. Statistical analysis involved calculating risk ratios with 95% confidence intervals and assessing heterogeneity with the I2 statistic.ResultsThe analysis included ten randomized control trials. Receiving outpatient hysteroscopy before undergoing ART was associated with increased live birth (RR 1.22, 95% CI 1.03–1.45, I2 61%) and clinical pregnancy rate (RR 1.27 95% CI 1.10–1.47, I2 53%). Miscarriage rates did not differ significantly (RR 1.25, CI 0.90–1.76, I2 50%). Subgroup analyses did not show a significant difference in clinical pregnancy rates when comparing normal versus abnormal hysteroscopic findings (RR 1.01, CI 0.78–1.32, I2 38%). We analyzed data using both intention-to-treat and per-protocol approaches, and our findings were consistent across both analytical methods.ConclusionsOffice hysteroscopy may enhance live birth and clinical pregnancy rates in infertile women undergoing ART, even when previous imaging studies show no apparent intrauterine lesions. Treating lesions not detected by imaging may improve ART outcomes. The most commonly missed lesions are endometrial polyps, submucosal fibroids and endometritis, which are all known to affect ART success rates. The findings suggested that hysteroscopy, given its diagnostic accuracy and patient tolerability, should be considered in the management of infertility.Database registrationThe study was registered in the International Prospective Register of Systemic Review database (CRD42023476403).

Metabolomics Integration in Assisted Reproductive Technologies for Enhanced Embryo Selection beyond Morphokinetic Analysis.

Embryo quality evaluation during in vitro development is a crucial factor for the success of assisted reproductive technologies (ARTs). However, the subjectivity inherent in the morphological evaluation by embryologists can introduce inconsistencies that impact the optimal embryo choice for transfer. To provide a more comprehensive evaluation of embryo quality, we undertook the integration of embryo metabolomics alongside standardized morphokinetic classification. The culture medium of 55 embryos (derived from 21 couples undergoing ICSI) was collected at two timepoints (days 3 and 5). Samples were split into Good (n = 29), Lagging (n = 19), and Bad (n = 10) according to embryo morphokinetic evaluation. Embryo metabolic performance was assessed by monitoring the variation in specific metabolites (pyruvate, lactate, alanine, glutamine, acetate, formate) using 1H-NMR. Adjusted metabolite differentials were observed during the first 3 days of culture and found to be discriminative of embryo quality at the end of day 5. Pyruvate, alanine, glutamine, and acetate were major contributors to this discrimination. Good and Lagging embryos were found to export and accumulate pyruvate and glutamine in the first 3 days of culture, while Bad embryos consumed them. This suggests that Bad embryos have less active metabolic activity than Good and Lagging embryos, and these two metabolites are putative biomarkers for embryo quality. This study provides a more comprehensive evaluation of embryo quality and can lead to improvements in ARTs by enabling the selection of the best embryos. By combining morphological assessment and metabolomics, the selection of high-quality embryos with the potential to result in successful pregnancies may become more accurate and consistent.

Evidence for Functional Roles of MicroRNAs in Lineage Specification During Mouse and Human Preimplantation Development.

Proper formation of the blastocyst, including the specification of the first embryonic cellular lineages, is required to ensure healthy embryo development and can significantly impact the success of assisted reproductive technologies (ARTs). However, the regulatory role of microRNAs in early development, particularly in the context of preimplantation lineage specification, remains largely unknown. Taking a cross-species approach, this review aims to summarize the expression dynamics and functional significance of microRNAs in the differentiation and maintenance of lineage identity in both the mouse and the human. Findings are consolidated from studies conducted using in vitro embryonic stem cell models representing the epiblast, trophectoderm, and primitive endoderm lineages (modeled by naïve embryonic stem cells, trophoblast stem cells, and extraembryonic endoderm stem cells, respectively) to provide insight on what may be occurring in the embryo. Additionally, studies directly conducted in both mouse and human embryos are discussed, emphasizing similarities to the stem cell models and the gaps in our understanding, which will hopefully lead to further investigation of these areas. By unraveling the intricate mechanisms by which microRNAs regulate the specification and maintenance of cellular lineages in the blastocyst, we can leverage this knowledge to further optimize stem cell-based models such as the blastoids, enhance embryo competence, and develop methods of non-invasive embryo selection, which can potentially increase the success rates of assisted reproductive technologies and improve the experiences of those receiving fertility treatments.

The “freeze-all” strategy seems to improve the chances of birth in adenomyosis-affected women

ObjectiveTo compare assisted reproductive technologies(ART) outcomes between fresh versus freeze-all strategies in infertile women affected with adenomyosis. DesignA single-center observational study SettingsUniversity hospital-based research center PatientsAdenomyosis-affected women undergoing blastocyst embryo transfer following in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) between 01/01/2018 and 31/11/2021. The diagnosis of adenomyosis was based on imaging criteria (i.e., transvaginal ultrasound and/or magnetic resonance imaging). Intervention(s)Women who underwent a freeze-all strategy were compared to those who underwent a fresh embryo transfer (ET) strategy.Main outcome measure(s): cumulative live birth rate (LBR) ResultsA total of 306 women were included in the analysis: 111 in the fresh ET group and 195 in the freeze-all group. The adenomyosis phenotype (internal diffuse adenomyosis, external focal adenomyosis, and adenomyoma) was not significantly different between the two groups. The cumulative LBR [86 (44.1%) vs. 34 (30.6%), respectively; p = 0.020] and the cumulative ongoing pregnancy rate [88 (45.1%) versus 36 (32.4%), respectively; p = 0.029] were significantly higher in the freeze-all group compared to the fresh ET group. After multivariate logistic regression analysis, the freeze-all strategy in women with adenomyosis was associated with significantly higher odds of live birth compared to fresh ET (OR = 1.80; 95% CI = 1.02–3.16). ConclusionThe freeze-all strategy in women afflicted with adenomyosis undergoing ART was associated with significantly higher cumulative live birth rates. Our preliminary results suggest that the freeze-all strategy is an attractive option that increase ART success rates. Additional studies, with a randomized design, should be conducted to further test whether the freeze-all strategy enhances the pregnancy rate in adenomyosis-affected women.

#289 : Mitochondrial Activator BGP-15 Protects Sperm from DNA Damage During Sperm Recovery for Assisted Reproductive Technology

Background and Aims: The recovery of sperm by assisted reproductive technology (ART) results in significant DNA damage. Elevated levels of DNA damage in sperm have been linked to poor-quality embryos and increased pregnancy loss after ART. Therefore, in this study, we aimed to investigate potential of the new mitochondrial activator BGP-15 to prevent sperm DNA damage in an in vitroejaculate over time. Additionally, we sought to determine whether BGP-15 can preserve sperm quality during various sperm recovery techniques used in ART. Method: We incubated donated human semen specimens untreated or treated with BGP-15, then examined sperm motility and DNA damage (DNA fragmentation and oxidation). Semen samples were then processed using different clinical sperm recovery methods: simple wash (SW), swim-up (SU) and density gradient centrifugation (DGC); and the purified sperm underwent further analysis including motility, vitality, ROS levels, mitochondrial membrane integrity and mitochondrial membrane potential (MMP), and DNA damage. Results: Semen samples incubated with BGP-15 demonstrated improved sperm motility and reduced DNA damage levels. SW samples had the highest sperm count, while SU had the highest vitality and DNA integrity, but the lowest MMP. DGC sperm had increased MMP after BGP-15 Treatment. Although BGP-15 treatment only reduced sperm DNA fragmentation in SW samples, it reduced DNA oxidation in all recovery methods. Conclusion: Our findings indicate that clinical manipulation of patient semen samples can negatively impact sperm quality, and different sperm recovery methods have unique effects. However, the addition of BGP-15 to clinical processes can preserve sperm quality, potentially leading to improved embryo quality and ART success.

Forty years of successful assisted reproductive technologies in Croatia

Forty years of successful assisted reproductive technologies in Croatia

#83 : Human Sperm Cryo-Survival Rate

Background and Aims: Sperm cryopreservation plays an important role in the suite of services available to fertility patients. The ability to preserve the motility and viability of human spermatozoa is a key component in delivering successful assisted reproductive technologies (ART) outcomes. Cryopreservation methods expose sperm to stress, resulting in cellular damage which consequently leads to a reduction in their survival rate. The aim of this study was to evaluate the average cryo-survival rate of semen samples frozen in a clinical setting, to help improve and manage patient expectations prior to accessing this service. Method: Pre and post sperm freeze data from patients who presented at the Genea Sydney clinic for sperm cryopreservation between 2017 and 2022 was analysed. The post-thaw survival rate for 1467 specimens was assessed by averaging the total post-thaw motility with total pre-freeze motility. Only ejaculated samples, frozen on-site, who had a raw motility calculated as well as a post-thaw motility analysis able to be performed were included in the study. Results: The range of post-thaw survival was 57% to 67% per annum over the six years of examined data, with an overall cryo-survival rate of 62%. Conclusions: The data shows a consistent recovery rate of post-thaw sperm motility over the time period analysed. Literature indicates average sperm cryo-survival rates range from 30% to 50%, and previous advice to patients has been to expect around 50% sperm survival. With this new data, Genea can revise its guidance to match the current average figure of around 60%. In addition, future internal freeze optimisation studies can use this figure as a benchmark to improve upon techniques and processes.

Transcriptomic signature of luteinized cumulus cells of oocytes developing to live birth after women received intracytoplasmic sperm injection

ObjectiveTo compare the transcriptome of human cumulus cells (CCs) from oocytes with different outcomes (pregnancy yes/no, live birth yes/no), to identify noninvasive biomarkers for oocyte selection as well as new therapeutic targets to increase live birth rates from assisted reproductive technologies (ART). DesignRetrospective observational study. SubjectsSubfertile couples undergoing controlled ovarian superstimulation and intracytoplasmic sperm injection (ICSI) with subsequent unbiopsied embryo transfer (ET) below the female age of 43 years. Intervention(s)RNA sequencing (RNA-seq) of CCs from oocytes resulting in a pregnancy, no pregnancy, live birth and no live birth. Main outcome MeasuresDifferential gene expression (DEG) between CCs of oocytes resulting in A) “no pregnancy” versus “pregnancy” and B) “pregnancy only” versus “live birth”. ResultsWhile RNAseq did not reveal DEGs when comparing the transcriptomic profiles of the groups “no pregnancy” with “ pregnancy”, we identified 139 DEGs by comparing “pregnancy only” with “live birth” of which 28 belonged to clusters relevant to successful ART outcomes (i.e. CTGF, SERPINE2, PCK1, HHIP, HS3ST, BIRC5). A functional enrichment analysis revealed that the transcriptome of CCs associated with live birth depicts pathways of extracellular matrix, inflammatory cascades leading to ovulation, cell patterning, proliferation and differentiation, and silencing pathways leading to apoptosis. ConclusionWe identified a CCs transcriptomic profile associated with live birth after ET that, after further validation, could serve to predict successful ART outcomes. The definition of relevant pathways of CCs related to oocyte competency contributes to a broader understanding of the cumulus oocyte complex to identify further therapeutic targets for improving ART success.

Risk factors for the ineffectiveness of assisted reproductive technology programs after a woman’s illness with COVID-19

Purpose - to determine the risk factors for the ineffectiveness of ART programs after a woman’s illness with COVID-19. Materials and methods. In the group of 80 examined patients with symptoms of “long-COVID” who applied to the reproductive technology clinic for infertility treatment, 2 subgroups were distinguished: the Subgroup 1: 64 patients in whom assisted reproductive technologies (ART) was unsuccessful (cancellation of transfer, non-occurrence of pregnancy or its loss) and the Subgroup 2: 16 women with successful ART (live birth). Results. Significant differences were found among patients with unsuccessful use of ART in terms of the frequency of the main symptoms of “long-COVID”, the following symptoms stand out: “depression, anxiety” (54.7% vs. 18.8%, p&lt;0.05) and “sleep disturbances” (59.4% vs. 31.3%, p&lt;0.05). A significant difference was also found in social and household factors: the presence of stress (35.9% vs. 12.5%, p&lt;0.05), especially in everyday life (31.3% vs. 6.3%, p&lt;0.05), the presence of bad habits (21.9% vs. 6.3%, p&lt;0.05). A significantly higher frequency of decreased ovarian reserve (32.8% vs. 12.5%, p&lt;0.05) and corresponding hormonal disorders: increased follicle-stimulating hormone (21.9% vs. 6.3%, p&lt;0.05) and decreased anti-Müllerian hormone (25.0% vs. 6.3%, p&lt;0.05). Among somatic pathology, endocrine pathology stands out (45.3% vs. 12.5%, p&lt;0.05), in particular metabolic disorders (34.4% vs. 12.5%, p&lt;0.05). A significant difference was also established in the frequency of liver diseases (21.9% vs. 6.3%, p&lt;0.05) and gastrointestinal tract (23.4% vs. 12.5%, p&lt;0.05). There is a higher frequency of menstrual disorders, namely a decrease in the duration of menstruation (20.3% vs. 6.3%) or, conversely, prolonged menstruation (17.2% vs. 6.3%), an irregular cycle (25.0% vs. 6.3%, p&lt;0.05) and luteal phase insufficiency (21.9% vs. 6.3%, p&lt;0.05). Urogenital infections were noted in 43.8% of patients (vs. 12.5%, p&lt;0.05). Conclusions. Risk factors for the ineffectiveness of ART programs have been established, among which stress, depression and anxiety, bad habits, endocrine pathology, metabolic disorders, liver pathology, menstrual cycle disorders, and urogenital infections are especially highlighted. The research was carried out in accordance with the principles of the Declaration of Helsinki. The research protocol was approved by the Local Ethics Committee of the institution mentioned in the work. Informed consent of the women was obtained for the research. No conflict of interests was declared by the authors.

Assisted reproductive technology use and outcomes in childhood cancer survivors.

Treatment exposures for childhood cancer reduce ovarian reserve. However, the success of assisted reproductive technology (ART) among female survivors is not well established. Five-year survivors of childhood cancer in the Childhood Cancer Survivor Study were linked to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System, which captures national ART outcomes. The authors assessed the live birth rate, the relative risk (RR) with 95% confidence intervals (95% CIs), and associations with treatment exposure using generalized estimating equations to account for multiple ovarian stimulations per individual. Siblings from a random sample of survivors were recruited to serve as a comparison group. Among 9885 female survivors, 137 (1.4%; median age at diagnosis, 10years [range, 0-20 years]; median years of follow-up after age 18 years, 11years [range, 2-11 years]) underwent 224 ovarian stimulations using autologous or donor eggs and/or gestational carriers (157 autologous ovarian stimulation cycles, 67 donor ovarian stimulation cycles). In siblings, 33 (1.4%) underwent 51 autologous or donor ovarian stimulations. Of those who used embryos from autologous eggs without using gestational carriers, 97 survivors underwent 155 stimulations, resulting in 49 live births, for a 31.6% chance of live birth per ovarian stimulation (vs. 38.3% for siblings; p=.39) and a 43.9% chance of live birth per transfer (vs. 50.0%; p=.33). Prior treatment with cranial radiation therapy (RR, 0.44; 95% CI, 0.20-0.97) and pelvic radiation therapy (RR, 0.33; 95% CI, 0.15-0.73) resulted in a reduced chance of live birth compared with siblings. The likelihood of live birth after ART treatment in survivors was not affected by alkylator exposure (cyclophosphamide-equivalent dose, ≥8000mg/m2 vs. none; RR, 1.04; 95% CI, 0.52-2.05). Childhood cancer survivors are as likely to undergo treatment using ART as sibling controls. The success of ART treatment was not reduced after alkylator exposure. The results from the current study provide needed guidance on the use of ART in this population.

A decennial cross-sectional review of assisted reproductive technology in a Tertiary Hospital in Southwest Nigeria

BackgroundThe World Health Organization recommends that Assisted Reproductive Technology be complementary to other ethically acceptable solutions to infertility. Whereas fertility centres are increasing in number in urban regions of Africa, published reports of their performance are sparse. We present a 10-year review of assisted reproductive technology performed in a public tertiary centre in Lagos, Nigeria.MethodsThis was a hospital-based, retrospective, cross-sectional review of 604 women, over a 10-year period that had in-vitro fertilization or in-vitro fertilization with intra-cytoplasmic sperm injection at the Institute of Fertility Medicine, Lagos State University Teaching Hospital. Data obtained were expressed in descriptive statistics and Pearson correlation was used to determine the strength of linear relationship between two continuous variables at a significance level of p < 0.05.ResultsThe mean age of the women was of 37.7 ± 6.2 years and 89.7% had no previous parous experience. About 27.2% of the male partners had normal seminal fluid parameters while 4.6% had azoospermia. Median serum follicle stimulating hormone of the women was 8.1 IU/L and median serum anti-mullerian hormone was 6.3 pmol/L. There was weak positive correlation between age and serum follicle stimulating hormone (r = 0.306, p < 0.001); weak negative correlation between age and serum anti-mullerian hormone (r = -0.48, p < 0.001) and very weak correlation between body mass index and serum follicle stimulating hormone (r = 0.173, p = 0.011). In-vitro fertilization and intra-cytoplasmic sperm injection was the method of fertilization used in 97.4% of the cases and 81.8% of embryos formed were of good quality. Most women (94.5%) had 2 embryos transferred and 89.9% had day-5 embryo transfer done. About 1 in 4 of the women (143/604, 23.7%) had clinical pregnancy and 49.7% of women who got pregnant had delivery of a live baby at term while 11.9% had preterm delivery of a live baby.ConclusionDespite increasing use and success of assisted reproductive technology in south-western Nigeria, there is room for improvement in clinical pregnancy rates and live birth rates post- assisted reproductive technology. Complication rates are desirably low.

Does the decrease in E2 levels between the trigger of ovulation and embryo transfer affect the reproductive outcome in IVF-ICSI cycles?

This study aimed to evaluate the effect of the rate of decline in serum estradiol (E2) levels between hCG injection and the day of embryo transfer (ET) on the success of assisted reproductive technology (ART) in women with infertility of different etiologies. Women 20-45 years of age who underwent a standard GnRH antagonist or long agonist protocol and fresh ET during day 3 of their first ART cycle were included. Group 1 was diagnosed with low ovarian reserve, group 2 comprised high ovarian responders, and group 3 consisted of normal responders. Both groups were divided into four subgroups according to the decrease in E2 levels between the day of hCG injection and the day of ET. Subgroup A patients had a decrease of <20%, subgroup B a decrease of 20-40%, subgroup C a decrease of 41-60%, and subgroup D a decrease >60%. The primary outcome measure was the effect of an E2 decline, based on the measurement of E2 on the day of hCG administration and day of ET, on the implantation rate. The secondary outcome was the change in E2 values in these three groups. The study was conducted on 1.928 women. Of these, 639 were poor responders (group 1), 502 were high responders (group 2), and 787 women had a normal ovarian response (group 3). Patients with a 60% decrease in their E2 levels on the ET day after hCG had a lower live birth rate (LBR) and higher miscarriage rate (MCR), except normoresponders, in whom a similar decline was significant only with respect to MCR. We indicate that high ovarian responders who underwent fresh ET cycles with a 60% decrease in their E2 levels on the ET day after human chorionic gonadotropin had lower LBRs and higher miscarriage. However, in normoresponder women, this decline was only significant in miscarriage.

Assisted reproductive technology outcomes and gene expression in unexplained infertility patients.

Background: Unexplained infertility (UI) can be a frustrating and challenging diagnosis for doctors and couples as it can be difficult to understand why they are unable to conceive despite increasing diagnostic tools. Assisted reproductive technology (ART) procedures have been successfully applied to many couples aiming to overcome UI. However, they can be not only expensive but also require multiple cycles to achieve a successful pregnancy. The endometrium and the follicular fluid have been investigated as target tissues not only to determine the cause of UI but also to increase conception rates. Results: In this study, we analyzed the outcomes of ART in 223 UI couples and gene expression associated with DNA modification, cell death, immune response and senescence (TET1, TET2, BCL2, BAK1, HMGA2, IL-6, IL-8) in infertile women's endometrium and follicular fluid. We found significant differences in women who successfully got pregnant compared to women unable to conceive depending on age, duration of infertility, number of retrieved oocytes, zygotes, transferred embryos. Further, the expression of genes BAK1 (pro-apoptotic), TET2 (associated with epigenetic DNA modification) and IL-6 (associated with immune responses) were significantly higher in the endometrium of women who successfully got pregnant. Conclusion: Younger parental age couples showed higher ART success rates, shorter duration of infertility, higher number of retrieved oocytes, zygotes and transferred embryos. The gene expression analysis revealed significant changes in the endometrium depending on genes associated with cell death and immune response which were upregulated in females with diagnosed unexplained infertility.

Minor changes in the incidence of primary and secondary involuntary childlessness across birth cohorts 1916 to 1975, but major differences in treatment success.

There have been tremendous advances in assisted reproductive technologies (ARTs) over the past 50 years. The present study assessed infertility outcomes among women of reproductive age during this period. The seventh survey of the Tromsø Study (Tromsø7, 2015-16) recruited Tromsø residents aged 40-98 years. The questionnaire collected information on sociodemographics and infertility, as well as data from a wide range of validated health questionnaires. Primary involuntary childlessness was defined as reporting one or more of the following: the clinical definition of infertility (i.e., infertility period of >1 year), infertility examination, use of ART, and/or the birth of a child conceived during ART. Women with secondary involuntary childlessness were those who reported infertility experience and had least one naturally conceived child. Parous women without infertility experience were classified as fertile, and nulliparous women without infertility experience as voluntarily childless. The main exposure was birth cohort (1916-35, aged 80-98 years; 1936-45, aged 70-79 years; 1946-55, aged 60-69 years; 1956-65, aged 50-59 years; 1966-75, aged 40-49 years). The incidence of primary involuntary childlessness was significantly higher in the 1956-75 cohort (6.0%; 95% CI: 5.4-6.6) than the 1916-55 cohort (3.7%; 95% CI: 3.2-4.3). The incidence of secondary involuntary childlessness was higher than that of primary involuntary childlessness across all birth cohorts and was highest for the 1966-75 cohort (10%), with no differences observed across the other birth cohorts (6-7%). An increasing proportion of women from the oldest to the youngest birth cohorts reported infertility examination and ART. ART success increased substantially with time, reaching 58% for primary and 46% for secondary infertility in the 1966-75 cohort. Voluntarily childless women comprised 5-6% of the 1916-55 cohort and 9-10% of the 1956-75 cohort. There were minor differences in the incidence of primary and secondary involuntary childlessness across the 1916-75 cohorts. Advances in ART over the past 50 years comprised 2.0% and 3.3% of population growth in the 1956-65 and 1966-75 cohorts, respectively: a remarkable achievement.