Failed In Vitro Fertilization Cycles Research Articles

ОТНОШЕНИЕ НАСЕЛЕНИЯ РЕСПУБЛИКИ БЕЛАРУСЬ К ПРИМЕНЕНИЮ ЭКСТРАКОРПОРАЛЬНОГО ОПЛОДОТВОРЕНИЯ

Purpose. To identify the attitude and stereotypical perception of the population about the use of in vitro fertilization (IVF) in the Republic of Belarus. Material and methods. A sociological survey of a representative republican sample, which consisted of 1805 respondents (851 (47%) men, 954 (53%) women) aged 18 to 65 years, was performed. Results. In general, there is a positive attitude on the part of society towards reproductive technologies (21.6% of respondents claimed absolutely positive attitude and 30.2% had rather positive attitude to IVF; a neutral attitude was revealed in 37.1% of respondents). Some of the population retain stereotypes associated with varying degrees of influence of reproductive technologies on the psychophysical health of children (about 34%). Conclusion. A system of measures is needed to improve the preparation of married couples with an established diagnosis of infertility and the ineffectiveness of other treatment methods for artificial conception. This approach will minimize the number of failed IVF cycles and reduce the risk of complications for the mother and child. The effective use of assisted reproductive technologies (ART) with positive outcomes in overcoming infertility will contribute to the formation of a positive attitude towards reproductive technologies on the part of society.

Clinical utility of office hysteroscopy following failed invitro fertilization-embryo transfer: A retrospective cohort study.

Despite its widespread use, invitro fertilization (IVF) outcomes are challenged by implantation failure, largely due to factors such as embryo quality and endometrial receptivity. In this study, we investigated the clinical effect of office hysteroscopy (OH) on the subsequent frozen-thawed embryo transfer (FET) in infertile women who experienced a failed IVF-embryo transfer (IVF-ET) cycle. We included 577 infertile women who underwent OH because of a history of failed ET between October 2019 and September 2021. During OH, visible endometrial polyps (EPs) were diagnosed and removed by curette or biopsy forceps; chronic endometritis (CE) was diagnosed by histopathology and immunohistochemistry and treated with oral doxycycline (0.2 g/d) for 14 days. According to the hysteroscopic findings and endometrial pathology with immunohistochemistry, patients were divided into three groups: group A (n = 161) had CE with or without EPs, group B (n = 156) had EPs only, and group C (n = 260) had no CE or EPs. In the following FET cycle, the implantation rates were 47%, 51%, and 45% (P = 0.411); the clinical pregnancy rates were 56%, 62%, and 55% (P = 0.436); the live birth rates were 45%, 51%, and 42% (P = 0.205); and the miscarriage rates were 18%, 16%, and 22% (P = 0.497) in groups A, B, and C, respectively. There were no significant differences among groups (P > 0.05). OH is helpful for diagnosis and treatment of abnormal intrauterine environment in women with a failed IVF cycle and further improves their pregnancy outcome in the following FET.

Oocyte in-vitro maturation primed with letrozole-HCG versus FSH-HCG in women with oocyte maturation abnormalities: a retrospective study

Research QuestionThe objective of this study was to compare letrozole-hCG primed IVM with FSH-hCG primed IVM in women with oocyte maturation abnormalities (OMAs) defined as at least two failed in vitro fertilization (IVF) cycles where immature oocytes were retrieved. DesignThis retrospective study was conducted at a private fertility clinic from January 2009 to April 2023. The final analysis included 75 women in Group 1 (FSH-hCG primed IVM) and 52 women in Group 2 (letrozole-hCG IVM). Result(s)Group 1 demonstrated a significantly higher median number of oocytes obtained [9, (IQR: 1-5) vs. 5 (IQR: 1-18)] (p<0.001). However, the groups had no differences in oocyte maturation stages at collection (p>0.05). At the end of IVM, group 1 had 73/666 mature oocytes, while group 2 had 106/322 mature oocytes, and the median MII oocyte rate per patient was higher in group 2 [33.3%, (IQR: 66.7-100.0%) vs. 0.0%, (IQR: 0.0-22.2%)] (p<0.001). Moreover, Group 2 demonstrated a higher median fertilization rate [66.7%, (IQR: 50.0-100.0%) vs. 50.0%, (IQR: 0.0-66.7%)] (p=0.027). The group 2 had a higher proportion of Grade 1 (17.1% vs. 0%) and Grade 2 (58.5% vs. 6.3%) embryos (p<0.001). Notably, all pregnancies obtained in the study were in Group 2 (5 vs. 0; p=0.042). Conclusion(s)IVM with Letrozole-hCG priming in women with prior failed IVF cycles due to OMAs may result in mature oocytes, clinical pregnancies, and live births. The effectiveness of letrozole priming IVM on the subtypes of OMAs need further investigation with studies including higher number of cases.

A pathogenic variant in the uncharacterized RNF212B gene results in severe aneuploidy male infertility and repeated IVF failure.

Quantitative and qualitative spermatogenic impairments are major causes of men's infertility. Although invitro fertilization (IVF) is effective, some couples persistently fail to conceive. To identify causal variants in patients with severe male infertility factor and repeated IVF failures, we sequenced the exome of two consanguineous family members who underwent several failed IVF cycles and were diagnosed with low sperm count and motility. We identified a rare homozygous nonsense mutation in a previously uncharacterized gene, RNF212B, as the causative variant. Recurrence was identified in another unrelated, infertile patient who also faced repeated failed IVF treatments. scRNA-seq demonstrated meiosis-specific expression of RNF212B. Sequence analysis located a protein domain known to be associated with aneuploidy, which can explain multiple IVF failures. Accordingly, FISH analysis revealed a high aneuploidy rate in the patients' sperm cells and their IVF embryos. Finally, inactivation of the Drosophila orthologs significantly reduced male fertility. Given that members of the evolutionary conserved RNF212 gene family are involved in meiotic recombination and crossover maturation, our findings indicate a critical role of RNF212B in meiosis, genome stability, and in human fertility. Since recombination is completely absent in Drosophila males, our findings may indicate an additional unrelated role for the RNF212-like paralogs in spermatogenesis.

P-329 Oocyte donation outcomes in endometriosis patients with multiple IVF failures

Abstract Study question What are the reproductive outcomes and the prognostic factors of live birth rates in endometriosis patients referred to oocyte donation after multiple in vitro fertilization(IVF)-failures? Summary answer In this specific population, oocyte donation appears to be a viable option to optimize the reproductive outcomes, as the cumulative live birth rate reaches 63.2%. What is known already Assisted Reproductive Technology(ART) is currently recognized as one of the main therapeutic options to manage endometriosis-related infertility, often resulting in satisfactory outcome. A burning issue in this field remains how to deal with patients undergoing recurrent ART failures. As there appear to be two main factors contributing to the failures, i.e., a deleterious effect of endometriosis on embryo implantation and altered oocyte and embryo quality, two competing therapeutic strategies can be considered:(i) endometriosis surgery and (ii) oocyte donation. However, no data has been published to date in the specific population of endometriosis patients with previous IVF failures, undergoing oocyte donation. Study design, size, duration Observational cohort study including fifty-seven women with endometriosis-related infertility and multiple IVF failures (≥ 2 failed IVF cycles) referred to oocyte donation who consulted at our institution between January 2013 and June 2022. Participants/materials, setting, methods Endometriosis was diagnosed based on published imaging criteria using transvaginal sonography and magnetic resonance imaging and confirmed histologically in women who had a history of surgery for endometriosis. The main outcomes measured were the clinical pregnancy rate (CPR) and the cumulative live birth rate (CLBR). We compared the characteristics of women who had a live birth versus those who did not using univariate and multivariate analysis to identify determinant factors of fertility outcome. Main results and the role of chance Fifty-seven patients underwent 90 oocyte donation cycles, after 244 failed autologous IVF cycles. The mean age of the population was 36.8 ± 3.3 years, with a mean infertility duration of 3.6 ± 2.2 years, and a mean number of autologous IVF/ICSI cycles of 4.4 ± 2.3 cycles per patient. Three patients (5.3%) had superficial endometriosis, 2 patients (3.5%) had ovarian endometriomas, and 52 patients (91.2%) had deep infiltrating endometriosis, among which 30 patients (57.7%) had bowel lesions. Thirty patients (52.6%) had associated adenomyosis. Overall, the CPR and the CLBR per patient were 49/57 (85.9%) and 36/57 (63.2%), respectively. After multivariate analysis, only being nulligravida (p = 0.002) remained an independent negative predictive factor of the live birth rate. Limitations, reasons for caution In 35.1% of patients there was no surgical/histological proof of endometriosis. However, for all the study participants, endometriosis was diagnosed and staged using patient interviews, clinical examination, and imaging techniques to assess for endometriosis phenotypes, which is in line with the structured diagnostic process acknowledged as being appropriate for endometriosis. Wider implications of the findings In this specific population, poor embryo quality may be the main limiting factor of ART success rates, rather than impaired endometrial receptivity. These data are reason for clinicians not to systematically refer infertile endometriosis patients with recurrent IVF failures to surgery. Trial registration number not applicable

Adding a ketogenic dietary intervention to IVF treatment in patients with polycystic ovary syndrome improves implantation and pregnancy

Patients with polycystic ovary syndrome (PCOS) on a high-carbohydrate diet intrinsically suffer from exacerbated glucotoxicity, insulin resistance (IR), and infertility. Lowering the carbohydrate content has improved fertility in patients with IR and PCOS; however, the effects of a well-controlled ketogenic diet on IR and fertility in PCOS patients undergoing in vitro fertilization (IVF) have not been reported. Twelve PCOS patients with a previous failed IVF cycle and positive for IR (HOMA1-IR>1.96) were retrospectively evaluated. Patients followed a ketogenic diet (50 g of total carbohydrates/1800 calories/day). Ketosis was considered when urinary concentrations were > 40 mg/dL. Once ketosis was achieved, and IR diminished, patients underwent another IVF cycle. The nutritional intervention lasted for 14 ± 11 weeks. Carbohydrate consumption decreased from 208 ± 50.5 g/day to 41.71 ± 10.1 g/day, which resulted in significant weight loss (−7.9 ± 1.1 kg). Urine ketones appeared in most patients within 13.4 ± 8.1 days. In addition, there was a decrease in fasting glucose (−11.4 ± 3.5 mg/dl), triglycerides (−43.8 ± 11.6 mg/dl), fasting insulin (−11.6 ± 3.7 mIU/mL), and HOMA-IR (−3.28 ± 1.27). All patients underwent ovarian stimulation, and compared to the previous cycle, there was no difference in oocyte number, fertilization rate, and viable embryos produced. However, there was a significant improvement in the implantation (83.3 vs. 8.3 %), clinical pregnancy (66.7 vs. 0 %), and ongoing pregnancy/live birth rates (66.7 vs. 0 %). Here, restriction in carbohydrate consumption in PCOS patients induced ketosis, improved key metabolic parameters, and decreased IR. Even though this did not affect oocyte or embryo quality or quantity, the subsequent IVF cycle significantly improved embryo implantation and pregnancy rates.

Intraovarian platelet-rich plasma administration could improve blastocyst euploidy rates in women undergoing in vitro fertilization.

ObjectivePlatelet-rich plasma (PRP) therapy has received a considerable attention as an adjunct to fertility treatments, especially in women with very low ovarian reserve and premature ovarian insufficiency. Although recent studies have demonstrated that PRP led to improvements in folliculogenesis and biomarkers of ovarian reserve, the effect of intraovarian PRP administration on embryo genetics has not been studied.MethodsWe report a pilot study of patients who had preimplantation genetic testing for aneuploidy (PGT-A) before and then within 3 months following PRP administration. Twelve infertile women with at least one prior failed in vitro fertilization (IVF) cycle underwent ovarian stimulation (cycle 1) with a gentle stimulation protocol and PGT-A performed at the blastocyst stage. Following cycle 1, autologous intraovarian PRP administration was performed. Within 3 months following PRP administration, the patients underwent cycle 2 and produced blastocysts for PGT-A. The percentage of euploid embryos between both cycles was compared.ResultsThe mean age of all participants was 40.08±1.46 years, and their mean body mass index was 26.18±1.18 kg/m2. The number of good-quality embryos formed at the blastocyst stage was similar between cycle 1 and cycle 2 (3.08±0.88 vs. 2.17±0.49, respectively; p=0.11). Among all patients in cycle 1, 3 of 37 embryos were euploid (8.11%) while in cycle 2, 11 out of 28 embryos were euploid (39.28%, p=0.002). Three clinical pregnancies were noted among this patient group.ConclusionThis novel study is the first to present an improvement in the embryo euploidy rate following intraovarian PRP application in infertile women with prior failed IVF cycles. The growth factors present in PRP may exhibit a local paracrine effect that could improve meiotic aberrations in human oocytes and thus improve euploidy rates. Whether PRP improves live birth rates and lowers miscarriage rates remains to be determined in large trials.

P-663 Dydrogesterone + progesterone gel vs. subcutaneous aqueous progesterone + progesterone gel for luteal phase supplementation in IVF cycles in women with previous IVF failure

Abstract Study question Does the live birth rate differ between the two regimens for luteal phase supplementation in IVF cycles in women with a history of IVF failure? Summary answer The live birth rate did not differ with dydrogesterone + progesterone gel vs. subcutaneous aqueous progesterone + progesterone gel. What is known already Supplementation of the luteal phase in in vitro fertilization (IVF) cycles is crucial to increase the chance of a live birth. Progesterone is the treatment of choice due to a lower risk of complications compared to human chorionic gonadotropin (hCG) and gonadotropin-releasing hormone (GnRH) analogues. There is no preferred progestogen for use in the general population of women undergoing IVF. The optimal progesterone treatment regimen in the event of previous IVF failure is unknown. Study design, size, duration A prospective randomized tertiary single-center study was conducted. The study included 161 women, aged 25-43 years, with FSH on cycle day 2-4 ≤10 IU/L, with at least one failed IVF cycle, undergoing government-funded IVF in the years 2015-2016. Participants/materials, setting, methods 161 included women were randomized after oocytes retrieval to 2 groups of luteal IVF cycle phase supplementation: dydrogesterone (Duphaston®) + progesterone in vaginal gel (Crinone®) or aqueous progesterone solution in subcutaneous injection (Prolutex®) + progesterone in vaginal gel (Crinone®). At least one blastocyst was obtained in the enrolled women. All women underwent fresh embryo transfer. After viable pregnancy confirmation, treatment was continued until the 12th week of gestation. Main results and the role of chance The indications for IVF were: male factor (51%), tubal factor (27%), endometriosis (24%), decreased ovarian reserve (17%), idiopathic infertility (14%), ovulation disorders (6%), occurring in various combinations. Out of 161 women enrolled in the study, 94 had a history of 1 failed IVF cycle, and 67 had at least 2 failed IVF cycles. Among 94 women with 1 failed IVF, 62 received dydrogesterone + progesterone gel vs. 32 aqueous progesterone + progesterone gel, and the percentages of live births, clinical pregnancies and biochemical pregnancies were: 29 vs. 21% (p = 0.37), 10 vs. 6% (p = 0.53), 5 vs. 12% (p = 0.21). Among 67 women with at least 2 failed IVFs, 24 received dydrogesterone + progesterone gel vs. 43 aqueous progesterone + progesterone gel, and the percentages of live births, clinical pregnancies and biochemical pregnancies were: 17 vs. 32% (p = 0.19), 4 vs. 0% (p = 0.14), 9 vs. 9% (p = 0.95). The results were comparable with both treatment regimens. There were no significant adverse events reported for both treatment regimens. Limitations, reasons for caution The limitations of the study are the small sample size, its single-center character and heterogeneity of indications for IVF. Wider implications of the findings In light of the lack of evidence of greater efficacy of either of the two luteal phase supplementation regimens of the IVF cycle in women with a history of IVF failure, the choice of treatment should be guided by other considerations, i.e. potential side effects, dosing convenience and patient preference. Trial registration number 1072.6120.47.2021

Evaluation of IL-1β and TNF-α level in endometrial flush in patients with recurrent implantation failure

Infertility is defined as the inability to conceive within a year of regular unprotected intercourse affecting one in six couples. The most common causes of infertility are ovulatory dysfunction, male factor infertility, and tubal disease [1]. Unexplained Infertility (UI) and Recurrent Implantation Failure (RIF) are diagnoses based on failed pregnancy attempts with current infertility treatment options. UI is diagnosed when testing is inconclusive and RIF is diagnosed after three failed In Vitro Fertilization (IVF) cycles. UI is the absence of conception despite 12 months of unprotected intercourse, not explained by anovulation, poor sperm quality, tubal pathology or other known cause of infertility. RIF is defined by three failed IVF cycles in which one or two high-quality embryos are transferred in each cycle or by two failures in oocyte donor recipients after the transfer of good quality embryos [1]. UI is a common cause of infertility affecting 10-30% of infertile couples [2], while RIF is present in around 10% of in vitro fertilization (IVF) cycles [3].

Validation of the existence of genuine Empty follicle syndrome, versus false empty follicle syndrome to make definitive decisions in cases where recurrent IVF failure encountered secondary to absence of oocytes on ovum pick up-a short communication

Aim: Worldwide a big altercation exists with regards to the actual existence of the term “ Empty follicle syndrome’’(EFS), so much so that certain big authorities in the field have been believing that true EFS does not exist. Basically EFS is a syndrome when no functionally intact oocyte get retrieved when attempting an oocyte pick up (OPU) for a successful in vitro fertilization (IVF), however such patients encounter recurrent IVF failures. Since it is has become a big problem for the treating reproductive endocrinologist, besides the patient encountering recurrent IVF failures, it has become essential to differentiate the true EFS alias genuine Empty follicle syndrome (gEFS) from what is labeled today as the false empty follicle syndrome (fEFS). In view of the recently documented presence of mutations, gEFS got verified and appears to silence this biggest conflict that arose secondary to the existence of a false empty follicle syndrome(fEFS), where one could manage to get successful IVF outcomes subsequent to repeated hCG injections/ gonadotropin releasing hormone (GnRH) agonist in addition to pregnancy, with lot of clinicians believing there is no true term like EFS. Methods: Recently Yang et al., performed a study In tertiary a university based reproductive center in China that was comprised of a big cohort of patients that presented with gEFS. Genetic evaluation was conducted on 35 non correlated infertile patients who went through 16 failed IVF cycles in addition to oocyte degeneration, besides the subjects got a diagnosis of possessing a particular kind of EFS- cumulus oocytes complexes (COC’s) but possessed oocytes that were undergoing degeneration, with the utilization of whole –exome sequencing along with targeted Sanger sequencing. Results: Yang et al., found 22 innovative genetic variant of zona pellucida (ZP), genes in 18 subjects, that were inclusive of 20 variants in ZP 1 gene, 2 in ZP 2 gene in addition to 1 recurring variant in ZP3 gene that had been earlier documented. The homogenous /compound heterogenous ZP 1 mutations were inherited in an autosomal recessive manner, while the heterogenous variants of ZP 2 as well as ZP3 genes possessed an autosomal dominant manner of inheritance. Conclusions: These mutations were anticipated to be harmful in silico along with got further experimentally corroborated to be functionally null dependent on their ectopic expression in vitro. Thus with this further evidence that has been recently provided with regards to the existence of genuine Empty follicle syndrome (gEFS), it is significant for the youngsters to realize if they encounter similar cases after trial of rescue hCG injections / GnRH) agonist, not to further keep waiting, but evaluate further with regards to the existence of mutations for Zona Pellucida (ZP), ZP 1, ZP2 as well as ZP3 genes mutations, or LH/ chorionic gonadotropins receptor (LHCGR) gene mutation without subjecting the patient to repeated IVF, with her psychological as well as financial health in mind

P–695 Establishing predictors of the mode of conception in fertility patients presenting with a clinical pregnancy

Abstract Study question What are the predictors for pregnancies conceived spontaneously (SC), by ovulation induction+/-insemination (OI±IUI) or via In-Vitro Fertilization(IVF), and what proportion of pregnancies were conceived with each method? Summary answer Pregnancies were conceived by SC(27.7%), OI±IUI(33%) or IVF(39.2%).Unexplained infertility positively-predicted SC and OI±IUI-conceptions. Male factor-infertility demonstrated the opposite trend, positively predicting IVF. Endometriosis negatively-predicted SC. What is known already Spontaneous conception (SC) occurs regularly among infertility patients. Most studies have evaluated predictors of pregnancy among women with infertility who were trying to conceive. Few studies have addressed the role of different factors on the mode of conception in infertility patients who were pregnant. Factors found in some studies to be related with a SC were younger female age, shorter duration of infertility, fewer failed IVF cycles, and diagnosis of unexplained-infertility. Study design, size, duration We conducted a retrospective cohort study at a University fertility-center over a six-month period in 2019 and 2020. We reviewed viability scans of 285-patients. Mode of conception was recorded as Spontaneous, OI±IUI, or IVF. Patients’ demographics, obstetric and fertility diagnosis as well as base-line hormones and ovarian reserve testing were extracted to calculate predictors for the mode of conception. Pregnancy was defined as an intra-uterine fetal sac on a transvaginal ultrasound in the 1st-trimester. Participants/materials, setting, methods Parametric analysis was done using ANOVA and Tukey’s post-hoc test. Nonparametric analysis was performed using the chi-square test. Predictors of the mode of conception were calculated by multivariate regression analysis using the variables not in the equation model including the following parameters: male and female age, gravidity, parity, ectopic-pregnancies, infertility diagnosis, baseline serum: FSH, estradiol, TSH, AMH, and AFC. Data is presented as mean ±SD or percentage. P &amp;lt; 0.05 was significant. IRB approval was obtained. Main results and the role of chance 79 (27.7%) of pregnancies were SC, 94 (33%) resulted from OI±IUI, and 112 (39.2%) from IVF. Demographics didn’t differ between the groups including: female age(p = 0.06), male age(p = 0.79), gravidity (p = 0.47), parity(p = 0.7), ectopic-pregnancies(p = 0.07), baseline serum FSH(p = 0.29), estradiol(p = 0.65), TSH(p = 0.56), AMH(p = 0.42), and AFC(p = 0.06). Infertility diagnoses differed when comparing SC, OI±IUI and IVF conceptions respectively: Unexplained (22.7%, 22.3%, 15.1%, p = 0.03), Male-Factor(MF) (25%, 27.6%, 42.8%, p = 0.042), Tubal-factor (2.5%, 2.1%, 13.4, p = 0.002) and Ovulation-disorders/PCOS (24%, 32%, 12.5% p = 0.002). Endometriosis trended higher in women with IVF (p = 0.09). A positive predictor for SC was unexplained infertility(p = 0.0001). A negative predictor was endometriosis(p = 0.005). SC was sub-significantly less likely in the presence of MF (p = 0.057). Unexplained-infertility was a positive predictor for OI±IUI pregnancies(p = 0.047), whereas MF was a negative predictor(p = 0.0001). As for IVF-conceptions, MF was a positive predictor(p = 0.008), while unexplained-infertility negatively predicted conception by IVF(p = 0.018). Ovulation-disorders/PCOS trended lower in women with IVF (p = 0.052). While baseline serum estradiol levels were similar between groups (means 194–218pmol/L), multivariate regression showed it to be a predictor for OI±IUI and IVF conceptions. The clinical significance of this finding is not clear. Interestingly, female age and ovarian reserve were not found to predict one type of conception over another. Other possible predictors in the model were not significant. Limitations, reasons for caution This retrospective cohort may hide underlying bias. Clinical pregnancies were evaluated and not live birth. Our cohort represents patients that conceived and do not offer information about the entire sub-fertile population that is treated in our center, which is also a strength as it’s a novel way of evaluating predictors. Wider implications of the findings: Among patients that conceived spontaneously, advanced age and ovarian reserve did not play a negative role. Predictors of pregnancy were confirmed as expected with the majority of unexplained infertility conceptions occurring spontaneously or with OI+/-IUI, patients with Male factor infertility often conceived by IVF, and ovulation disorders by OI+/-IUI. Trial registration number NA

Микробиом эндометрия у женщин с многократными неудачами экстракорпорального оплодотворения

Objective. To assess endometrial microbiome in women with infertility and multiple failed in vitro fertilization (IVF) cycles. Patients and methods. The study included 42 women; group 1 consisted of 22 women aged 20 to 42 with infertility and repeated unsuccessful IVF cycles; in group 2 (control), there were 20 healthy women aged 20 to 42 years, planning pregnancy. Microbiome samples for the study were taken from 20 to 24 days of the menstrual cycle. Results. Higher relative concentrations of Lactobacillus iners, Lactobacillus acidophilus, Lactobacillus jensenii, Lactobacillus crispatus, Prevotella melaninogenica, Bacteroides vulgatus, Corynebacterium bouchesdurhonense, Bacteroides caccae, Bifidobacterium gallinarum, Bifidobacterium adolescentis were revealed in the group of healthy women without aggravating factors in obstetric and gynecological medical history. Higher relative concentrations of Methylobacterium aerolatum and Comamonas testosteroni were found in women in group 1. A distinctive feature of endometrial microbiota in women in this group was the presence of Streptococcus spp. and Gardnerella vaginalis in low concentrations. The average relative representation of the genus Lactobacillus was 34.4% in group 1 and 63.0% in group 2. In general, the composition of the uterine microbiome contained bacteria characteristic of oral and intestinal biotopes. Conclusion. Women with multiple failed IVF cycles have greater biodiversity than healthy women. The presence of high concentrations of Lactobacillus may be a marker of favorable reproductive outcomes. Key words: endometrial microbiome, failure, in vitro fertilization, Lactobacillus

PD25-01 DOES THE USE OF TESTICULAR SPERM IMPROVE OUTCOMES IN NON-AZOOSPERMIC COUPLES WITH PREVIOUS IN-VITRO FERTILIZATION (IVF) FAILURE USING EJACULATED SPERM?

You have accessJournal of UrologyInfertility: Epidemiology & Evaluation II (PD25)1 Apr 2020PD25-01 DOES THE USE OF TESTICULAR SPERM IMPROVE OUTCOMES IN NON-AZOOSPERMIC COUPLES WITH PREVIOUS IN-VITRO FERTILIZATION (IVF) FAILURE USING EJACULATED SPERM? M. Blake Evans, Jessica Marinaro*, Allison Eubanks, Kate Devine, Micah Hill, Alan DeCherney, Russell Hayden, Paul Shin, and Cigdem Tanrikut M. Blake EvansM. Blake Evans More articles by this author , Jessica Marinaro*Jessica Marinaro* More articles by this author , Allison EubanksAllison Eubanks More articles by this author , Kate DevineKate Devine More articles by this author , Micah HillMicah Hill More articles by this author , Alan DeCherneyAlan DeCherney More articles by this author , Russell HaydenRussell Hayden More articles by this author , Paul ShinPaul Shin More articles by this author , and Cigdem TanrikutCigdem Tanrikut More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000882.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The use of testicular sperm for prior in-vitro fertilization (IVF) failure has been shown to have higher clinical pregnancy rates (CPR), live birth rates (LBR), and reduced spontaneous abortion (SAB) rates compared to ejaculated sperm (ES). However, some argue that this treatment is an invasive surgical procedure without clear benefit. This study evaluates the outcomes of IVF-intracytoplasmic sperm injection (ICSI) cycles using testicular sperm in non-azoospermic couples with prior IVF failure(s) using ES. METHODS: From 1/2015 to 10/2019, 116 non-azoospermic couples with ≥1 prior IVF cycle using ES underwent testicular sperm extraction (TESE) for IVF/ICSI. Failed cycles with ES were defined as those not progressing to clinical pregnancy. Outcomes using TESE sperm were compared to the mean values of couples’ prior cycles using ES. Primary outcomes included clinical pregnancy rates (CPR) and live birth rates (LBR). Secondary outcomes included fertilization and blastocyst conversion. RESULTS: Among 116 couples, the average number of prior failed IVF cycles using ES was 2.3 (range: 1-8). A total of 140 IVF/ICSI cycles were performed using TESE sperm (116 fresh TESE sperm, 24 frozen/thawed TESE sperm). Of these, there were 71 fresh blastocyst transfers, 31 frozen blastocyst transfers (FET), and 38 cycles without transfer. There were also 9 FETs using supernumerary embryos, for a total of 111 embryo transfers. Compared to ES, IVF/ICSI using TESE sperm significantly improved blastocyst development (p=0.003), blastocyst conversion (p=0.003) and number of embryos available for vitrification (p=0.003). A subset of men (n= 66) had a sperm DNA fragmentation (SDF) assessment of ES. Mean SDF was 45% (7- 90%). Of these 66 men, 55 (83%) had an SDF >25%. The outcomes for patients with elevated SDF did not differ significantly from the overall cohort. CONCLUSIONS: In non-azoospermic couples with prior failed IVF cycles using ES, IVF/ICSI using TESE sperm may improve embryo development, CPR and LBR. Testicular sperm may avoid the adverse effects of elevated SDF from ES and improve pregnancy outcomes in some patients. Further randomized studies are needed to determine if such a benefit exists. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e538-e538 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information M. Blake Evans More articles by this author Jessica Marinaro* More articles by this author Allison Eubanks More articles by this author Kate Devine More articles by this author Micah Hill More articles by this author Alan DeCherney More articles by this author Russell Hayden More articles by this author Paul Shin More articles by this author Cigdem Tanrikut More articles by this author Expand All Advertisement PDF downloadLoading ...

Spontaneous pregnancies in patients with at least one failed IVF cycle after the management of autoimmune disorders, hereditary thrombophilia, and methylation disorders.

Objective:This study aimed to describe the impact on achieving spontaneous pregnancy of treating patients with at least one failed in-vitro fertilization (IVF) cycle for autoimmune disorders, hereditary thrombophilia, and methylation disorders.Methods: Fifty-three patients who met the enrollment criteria seen between January 2007 and October 2017 were included in this retrospective cohort study. The patients were retrospectively assessed for the presence of hereditary thrombophilia, methylenetetrahydrofolate reductase (MTHFR) polymorphisms, serum vitamin B12/folate/homocysteine levels, and autoimmune antibody positivity. The required data were extracted from the institutional patient database. Statistical analyses were performed on Statistical Package for the Social Sciences (SPSS.22®). The Kolmogorov-Smirnov test was used to evaluate the distribution of the data, and since the data did not following a normal distribution, proportions and median (minimum-maximum) values were used.Results:The 53 patients included in the study had singleton pregnancies. The distribution of autoantibodies was as follows: thyroid peroxidase (n=17); antithyroglobulin (n=11); double-stranded DNA (n=4); antinuclear (n=8); anti-smooth muscle (n=1); and anticardiolipin IgG and IgM (n=1). Autoimmune diseases included Hashimoto's thyroiditis (n=23); SLE (n=7); Behcet's disease (n=1); Sjogren's syndrome (n=1); ulcerative colitis (n=1); and anti-phospholipid antibody syndrome (n=1). Ten patients had heterozygous Factor V Leiden thrombophilia; two had homozygous Factor 5 Leiden thrombophilia; and three had the prothrombin 20210A heterozygous mutation. Twenty-eight patients were positive for autoantibodies and hereditary thrombophilia and/or MTHFR polymorphisms.Conclusions:Evaluation and management of hereditary thrombophilia, MTHFR gene polymorphisms, and/or autoimmune conditions may be beneficial for patients with unexplained infertility.

The impact of intentional endometrial injury on reproductive outcomes: a systematic review and meta-analysis.

Endometrial injury is an intentional damage made to the endometrium, usually produced by a Pipelle catheter. Over the last two decades, endometrial injury has been studied to improve implantation rates and decrease the incidence of implantation failure in invitro fertilization (IVF) cycles. Recently, additional studies of endometrial injury, performed not only in patients with implantation failure but also in intrauterine insemination cycles, have been conducted, and the endometrial injury made by hysteroscopy has been researched. The evidence describing the impact of endometrial injury is controversial; therefore, we conducted a systematic review and meta-analysis to examine the issue. Our objective is to review the research that has been done until now and perform a meta-analysis regarding endometrial injury and its influence on implantation success and pregnancy rates in patients with at least one failed IVF cycle. In particular, we aim to study the efficacy of the procedure and look for confounding factors, such as maternal age, in assessing the efficacy of endometrial injury. The systematic review of the literature was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. Study protocol can be assessed at PROSPERO International prospective register of systematic reviews (registration number CRD42018092773). Searches were conducted by an experienced research librarian in the following databases: MEDLINE(R) using the OvidSP interface and PUBMED, Embase, Web of Science and Cochrane Library. This review considered for inclusion randomized-controlled trials examining the success of performing local endometrial injury on IVF outcomes in women with previous failed IVF cycles. Ten studies, comprising a total of 1260 patients, were selected. Overall, when studying the effect of endometrial injury on clinical pregnancy rates (CPRs) and live birth rates (LBRs), higher rates were shown in the endometrial injury group. However, endometrial injury did not significantly improve CPRs and LBRs, when considering sub-group analyses of studies including patients with two or more failed IVF cycles, studies examining older patients or studies which did not include hysteroscopy. There was no significant difference found regarding multiple pregnancy rates, while a handful of studies showed an improvement in miscarriage rates. Endometrial injury should be used restrictively and not routinely in clinics. Maternal age and number of previous failed treatment cycles may be contributing factors which can influence the results when studying the effect of endometrial local injury. It is possible that the relative contribution of endometrial receptivity to the chances of implantation decreases with any additional failed cycle. The optimal study to prove the efficacy of local endometrial injury on implantation and pregnancy rates, should be a random-controlled trial studying the effect of local endometrial injury in oocyte donation cycles, in recipients with repeated implantation failure. This kind of study will conclude whether local endometrial injury is an efficient procedure with minimum confounding factors, and may assist in defining the population, even outside of donation cycles, that will benefit from the procedure.

Role of Low Dose Intravenous Immunoglobulin in IVF Failure - A Retrospective Analysis

Background: In developing countries the number of in vitro fertilization (IVF) attempts is often limited by the high costs of the procedure and relatively low success rates. In such a setup we have tried to evaluate the effect of low dose intravenous immunoglobulins (IVIg) administered to patients who have had previous failed IVF outcomes. Bearing in mind that the inherent fecundity of Indian population is higher and thus a lower dose of IVIg may suffice to give positive outcomes at an affordable price, in this manner providing them with the possibility of affording more attempts if required. Objective: To evaluate the role of low dose intravenous immunoglobulin in IVF failure. Design: Retrospective analysis Materials and methods: This is a retrospective study beginning from 1st January 2014 till 31st December 2014. During this period, 124 patients with two or more failed IVF cycles were included. The controlled ovarian stimulation was started on cycle day 2 using gonadotropins (225 - 450 iu daily) and GNRH antagonist was added on the day when follicle reached 13 -14 mm. When follicles reached 18mm, transvaginal ultrasound guided oocyte aspiration was performed within 36 hours of the hcg trigger. On the ovum pick up day, 5 grams IVIg was administered to the patient as a slow infusion. Embryo transfer was done on day 2 or 3. Serum beta hcg was done 14 days after the embryo transfer and pregnancy rate and clinical pregnancy were evaluated. Results: The total pregnancy rate was 46% (57/124) and clinical pregnancy rate was 42.7% (53/124). Conclusion: Our study concluded that low dose IVIg may play a significant role in improving pregnancy rates in women with previous failed IVF attempts.

The effects of local endometrial injury by hysteroscopy on in vitro fertilization outcome

Bacngraund/Aim. Regardless of embryos quality, an appropriate endometrial thickness and a successful embryo transfer (ET), implantation remains a difficulty for a favorable outcome of an in vitro fertilization (IVF). Numerous studies with the aim of increasing implantation rate and pregnancy rate suggest local endometrial injury (LEI) prior to the IVF procedure. Hysteroscopy is a method becoming more widely used both with patients after a failed IVF cycle and with patients before the first IVF, considering the large incidence of uterus cavum pathological states which have a negative impact on the favorable outcome. However, there is still no consensus reached over LEI, the way and time of its performing or its impact. The aim of this research was to determine the effect of hysteroscopically made local endometrial lesion on the IVF procedure outcome, both in the first and in the next IVF cycle and also to examine if the new method of LEI provoking using bipolare electrode has a favorable impact on post IVF pregnancy success. Methods. Total of 81 patients had hysteroscopy performed 30? 50 days prior to IVF, 40 of which had LEI made during hysteroscopy (the LEI group) using bipolar electrode in a way not described in any available literature. Remaning histeroscopically treated patients (n = 41) had no LEI (the non-LEI group). The control group included 151 patient who had IVF performed with no prior hysteroscopy and LEI. Results. The rate of clinical pregnancies after LEI was statistically more significant in comparison to the control group (52.50% vs 34.44%, p &lt; 0.05) and it meant 2.1 time bigger chance to conceive (OR=2.10; 95% CI: 1.04 ? 4.26; p &lt; 0.05). We noticed differences in the implantation rate between the LEI group and the non-LEI group on one side and the control group on the other, in favor of the two groups subjected to hysteroscopy (23.89%, 25.47% vs 18.18%, respectively), but they were not of any statistical significance. Not significantly higher rate of pregnancy was present, after the first and the next IVF, both in the LEI and the non-LEI group when compared to the control one. Conclusion. New method of LEI provoking by bipolar electrode in the process of hysteroscopy is a simple and safe method allowing higher rate of clinical pregnancies and doubling the probabilty of the positive IVF outcome.

The dilemma of counseling patients about poor prognosis: live birth after IVF with autologous oocytes in a 43-year-old woman with FSH levels above 30mIU/mL.

Providing reasonable expectations to patients with diminished ovarian reserve prior to attempting pregnancy through in vitro fertilization (IVF) is one of the most challenging aspects of fertility care. In some instances, advice from the clinician to pursue more effective treatment, such as donor oocytes, may not be acceptable to the patient. In this case report, a patient is presented who represents a poor prognosis candidate for IVF treatment. She was 43years old with six prior failed IVF cycles and repetitive basal FSH values above 30mIU/mL. Presented are the challenges in patient counseling and decision making. In her seventh IVF cycle, which she was strongly counseled against pursuing, the patient experienced the desired outcome of live birth. Increasing reports are emerging of live birth using autologous oocytes among women of advanced reproductive age. These instances, as well as the case of our patient, raise issues commonly encountered in patient counseling in poor prognosis patients. This discussion should include an emphasis on patient goals as well as an acknowledgement that no test for ovarian reserve has a 100% positive predictive value.

Predictors of treatment failure in young patients undergoing in vitro fertilization.

The purpose of the study was to evaluate whether routinely collected clinical factors can predict in vitro fertilization (IVF) failure among young, "good prognosis" patients predominantly with secondary infertility who are less than 35years of age. Using de-identified clinic records, 414 women <35years undergoing their first autologous IVF cycle were identified. Logistic regression was used to identify patient-driven clinical factors routinely collected during fertility treatment that could be used to model predicted probability of cycle failure. One hundred ninety-seven patients with both primary and secondary infertility had a failed IVF cycle, and 217 with secondary infertility had a successful live birth. None of the women with primary infertility had a successful live birth. The significant predictors for IVF cycle failure among young patients were fewer previous live births, history of biochemical pregnancies or spontaneous abortions, lower baseline antral follicle count, higher total gonadotropin dose, unknown infertility diagnosis, and lack of at least one fair to good quality embryo. The full model showed good predictive value (c = 0.885) for estimating risk of cycle failure; at ≥80% predicted probability of failure, sensitivity = 55.4%, specificity = 97.5%, positive predictive value = 95.4%, and negative predictive value = 69.8%. If this predictive model is validated in future studies, it could be beneficial for predicting IVF failure in good prognosis women under the age of 35years.

Gender differences in emotional reactions to in vitro fertilization treatment: a systematic review.

The purposes of this paper are to provide a comprehensive picture of men and women's emotional reactions to infertility treatment, specifically In Vitro Fertilization (IVF) pursued by heterosexual couples, and to identify any differences between the genders. Nonexperimental studies exploring the psychological effects of IVF treatment on infertile couples were included. Six electronic databases were used to conduct a systematic search from the years 2000 to 2014. The references of the articles selected for review and other related systematic reviews were also screened to retrieve additional relevant articles. The quality of the included studies was assessed using the Joanna Briggs Institute Critical Appraisal Checklist. Descriptive analysis was adopted to synthesize the results. A total of 22 quantitative and 4 qualitative studies were identified and included in this review. Although both men and women experienced psychological distress during the treatment, gender differences existed. Women had elevated anxiety and depression levels prior to the treatment, which became even higher on the day of the oocyte retrieval, pre- and post embryo transfer, and during the waiting period before the pregnancy test. Men of the infertile couples reported elevated depression scores before treatment, which usually increased during the time spent waiting for the outcome of the IVF treatment. Both men and women had lower scores on positive affect before the pregnancy test. A failed IVF cycle had long-term negative psychological consequences for both spouses. The results of this review pointed to the need for a couple-based support program, aimed at improving the psychological well-being of couples.