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BACKGROUND: Repeated implantation failure (RIF) refers to the condition where high quality embryos are unable to successfully implant after multiple cycles of in vitro fertilization (IVF) treatment. The aim of this study is to investigate the impact of intrauterine granulocyte colony-stimulating factor (G-CSF) and platelet-rich plasma (PRP) on pregnancy rate in patients with RIF. MATERIALS AND METHODS: The present randomised clinical trial study was conducted at the IVF Centre of Mehr Medical Institute in Rasht, Iran, from 2020 to 2022. The research consisted of 200 individuals who had experienced multiple failed cycles. These patients were randomised into two groups: intrauterine infusion of 1 ml of G-CSF and intrauterine infusion of 1 ml autologous PRP at least 48 hours before embryo transfer (ET). The groups were compared in terms of implantation rate, and chemical, clinical, and ongoing pregnancy. RESULTS: The implantation rate was significantly higher in patients who received PRP (P=0.016). Chemical pregnancy in the PRP group was significantly higher than G-CSF group (P=0.003). Both clinical pregnancy and ongoing pregnancy rates were significantly higher in the PRP group (P=0.001) compared to the G-CSF group (P=0.02). CONCLUSION: The utilisation of PRP via intrauterine infusion is considerably more successful than G-CSF in enhancing pregnancy and live birth rates among patients with RIF.

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Background: In vitro fertilization (IVF) has revolutionized infertility treatment. Nevertheless, male infertility requires more effective solutions. In 1992, the first-ever case of human birth via intracytoplasmic sperm injection (ICSI) was reported. ICSI involves microscopically injecting a sperm into an ovum. Successful ICSI has become a reliable therapy for couples facing infertility, a significant milestone. However, it has also introduced various challenges. This study also delves into ethical dilemmas arising from widespread ICSI use. Methods: This review traces the history of ICSI, presenting pioneering attempts, first successful attempts, and critical reports on account of the initial skepticism toward the technology. The review also focuses on chronological progress until ICSI was recognized as effective and became widely applied. Main findings: The review reveals that ICSI, although transformative, presents challenges. Successes include addressing male infertility and aiding fertilization. However, concerns arise regarding optimal sperm and embryo selection, genetic mutations, and long-term health implications. Ethical considerations surrounding ICSI's broad applications also surface. Conclusions: Despite its success and effectiveness, ICSI is still evolving as a therapeutic method. By comprehensively evaluating the historical progress and the current status of ICSI and exploring its future prospects, this study highlights the importance of ICSI in infertility treatment.

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Objective: This study compared the outcomes of conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in patients with polycystic ovarian syndrome (PCOS), tubal factor (TF) infertility, and unexplained infertility whose partners had normal semen parameters. Methods: This retrospective study included 360 couples diagnosed with infertility involving PCOS (n=157), unexplained infertility (n=140), and TF infertility (n=63). Sibling oocytes were randomly assigned to undergo ICSI or conventional IVF insemination. The fertilization rate and embryo morphology were evaluated as outcomes. Results: Retrieved cumulus-oocyte complexes from patients with PCOS (2,974), unexplained infertility (1,843), and TF infertility (844) were split and inseminated by conventional IVF and ICSI respectively. In comparison to the ICSI method, the conventional IVF approach was linked to a significantly higher fertilization rate in groups with PCOS (68.81% vs. 77.49%), unexplained infertility (67.62% vs. 78.84%), and TF issues (69.23% vs. 78.63%) (p<0.05). The proportion of embryos with grade A produced by the conventional IVF method was significantly higher than that produced using the ICSI method in the PCOS and unexplained infertility groups (p<0.05). Additionally, the percentage of grade B embryos produced with the ICSI method was significantly higher than that produced with the conventional IVF method in PCOS patients (p=0.002). Conclusion: Our results indicated that the conventional IVF method was associated with higher zygote production and a higher proportion of grade A embryos when all infertile groups were evaluated together. Thus, ICSI is not suggested for patients with these causes of infertility if their partner has normal semen parameters.

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OBJECTIVE: To explore whether intracytoplasmic sperm injection (ICSI) would increase the malformation risk in fetuses and live births compared with conventional in vitro fertilization (IVF). DESIGN: Retrospective cohort study. PATIENT(S): Data were collected from couples who underwent conventional IVF or ICSI from January 2009 to December 2019 at the Center for Reproductive Medicine of Peking University Third Hospital in the People's Republic of China. A total of 46,167 conventional IVF fresh transfer cycles and 33,247 ICSI fresh transfer cycles were included. INTERVENTION(S): Intracytoplasmic sperm injection and conventional IVF. MAIN OUTCOME MEASURE(S): The primary outcomes were congenital abnormalities in live births. The secondary outcomes included the pregnancy outcomes, the malformations among the miscarriages, specific types of malformations in live births, birth weight, and sex. RESULT(S): The rates of congenital malformations in conventional IVF and ICSI were 5.44‰ and 5.78‰, respectively. There was no statistically significant difference between the two groups, as indicated by the adjusted odds ratio of 1.098 (95% confidence interval 0.787, 1.532). The rates of specific malformations were comparable between ICSI and IVF. Additionally, no discernible disparities were noted in pregnancy outcomes, the malformations among the miscarriages,birth weight between the two groups. CONCLUSION: Our study suggested the safety of ICSI and provided novel evidence by comparing pregnancy outcomes and congenital malformations in offspring between patients undergoing conventional IVF and ICSI.

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Purpose: The Japan Society of Obstetrics and Gynecology (JSOG) registry gathers comprehensive data from registered assisted reproductive technology (ART) facilities in Japan. Herein, we report 2021 ART cycle characteristics and outcomes. Methods: Descriptive statistics were used to summarize and analyze 2021 data. Results: In 2021, 625 ART facilities participated in the registry; 27 facilities did not conduct ART cycles and 598 registered treatment cycles. In total, 498 140 cycles were registered, and there were 69 797 neonates (increases of 10.7% and 15.5%, respectively, from the previous year). The number of freeze-all in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles decreased in 2021; the number of neonates born was 2268 for IVF-embryo transfer (ET) cycles and 2850 for ICSI cycles. Frozen-thawed ET (FET) cycles increased markedly from 2020 (11.2% increase). In 2021, 239 428 FET cycles were conducted, resulting in 87 174 pregnancies and 64 679 neonates. For fresh transfers, the total single ET, singleton pregnancy rate, and singleton live birth rates were 82.7%, 97.0%, and 97.3%; for FET, these rates were 84.9%, 96.9%, and 97.1%. Conclusions: The 2021 Japanese ART registry analysis showed marked increases in both total treatment cycles and live births from the previous year.

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OBJECTIVE: This study investigated the clinical and laboratory factors associated with the presence of dysmorphic oocytes in intracytoplasmic sperm injection (ICSI) cycles. METHODS: The study involved 200 ICSI cycles, performed from 2020 to 2021, that yielded at least one mature oocyte. Clinical characteristics and ovarian stimulation methods were compared between 68 cycles with at least one dysmorphic oocyte (the dysmorphic group) and 132 cycles with normal-form oocytes only (the non-dysmorphic group). Dysmorphic oocytes were characterized by dark cytoplasm, cytoplasmic granularity, cytoplasmic vacuoles, refractile bodies in the cytoplasm, smooth endoplasmic reticulum in the cytoplasm, an oval shape, an abnormal zona pellucida, a large perivitelline space, debris in the perivitelline space, or an abnormal polar body. RESULTS: The ages of the women, indications for in vitro fertilization, serum anti-Müllerian hormone levels, and rates of current ovarian endometrioma were similar between the dysmorphic and non-dysmorphic groups. In both groups, the three ovarian stimulation regimens, two types of pituitary suppression, and total gonadotropin dose were employed similarly. However, the dual-trigger method was used more frequently in the dysmorphic group (67.6% vs. 50%, p=0.024). The dysmorphic group contained significantly more immature oocytes and exhibited significantly lower oocyte maturity (50% vs. 66.7%, p=0.001) than the non-dysmorphic cycles. Within the dysmorphic group, significantly lower oocyte maturity was found in the cycles using a dual-trigger, but not in those with a human chorionic gonadotropin trigger. CONCLUSION: ICSI cycles with dysmorphic oocytes are closely associated with reduced oocyte maturity. This association was observed exclusively in dual-trigger cycles.

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OBJECTIVE: To describe the reproductive and obstetric outcomes of an intracytoplasmic sperm injection cycle with preimplantation genetic testing for aneuploidy in an advanced reproductive-age woman with high-grade mosaic Turner syndrome. METHODS: Case report of a 39-year-old woman diagnosed with mosaic Turner Syndrome 45,X[90]/46,XX[10] karyotype who underwent in vitro fertilization treatment with blastocyst trophectoderm biopsy for preimplantation genetic testing using next-generation sequencing. RESULT(S): Two of the four blastocysts biopsied were euploid. The patient achieved ongoing pregnancy after the first single euploid frozen embryo transfer, followed by the birth of a healthy child. CONCLUSION: Autologous intracytoplasmic sperm injection cycles can be considered in a select group of advanced reproductive-age women diagnosed with high-grade mosaic Turner syndrome.

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Objective: The aim of this study was to determine the role played by psychological distress in the relation between personality dimensions and pregnancy outcome of women undergoing in vitro fertilization/Intra-Cytoplasmic Injections (IVF/ICSI) treatment. Method : This prospective cohort study was conducted for 12 months on 154 infertile women who were receiving IVF/ICSI assisted reproductive treatment for the first time. Research instruments for measuring psychological distress included the Fertility Problem Inventory (FPI) and the Depression, Anxiety, and Stress Scale (DASS-21). One of these was completed prior to ovarian stimulation and the other during the embryo transfer stage. The temperament and Character Inventory-Revised (TCI-R 125) was employed once to assess personality dimensions prior to the ovarian stimulation stage. Independent t-test, Mann Whitney test, Repeated Measures and path analysis were performed for statistical analysis of data. Results: The results of this study showed no significant difference between the pregnant and non-pregnant groups in personality traits (Harm avoidance and self-directness) and psychological distress (FPI and DASS scores). Repeated measures showed a significant difference in stress, anxiety, and depression levels between the two stages of ovarian stimulation and embryo transfer (P < 0.01). Path analysis showed no significant direct and indirect effect for harm avoidance on the pregnancy outcome when psychological distress was mediated. Conclusion: The effect of psychological factors on IVF outcomes is more complicated than is generally assumed and more studies are mandatory to clarify the relationship between personality traits and infertility treatments.

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AIM: From April 2022, the Japanese government funding system for assisted reproductive technology (ART) has shifted from government subsidies to universal health insurance. To date, studies estimating the health care expenditure for ART are scarce. We estimated health care expenditures for ART cycles and compared the proportion of patients' out-of-pocket payment by ovarian stimulation protocols under the Japanese government subsidy system. METHODS: We linked payment information for government subsidies in Saitama Prefecture during 2016 and 2017 with the Japanese ART registry. Health care expenditures for all treatment cycles in Japan during 2017 among women aged <43 years (n = 369 757) were estimated using a generalized linear model. RESULTS: We linked 6269 subsidy applications to the Japanese ART registry. The average treatment fee for a fresh cycle was 376 434 JPY (standard deviation = 159 581). However, significant variation was observed across ovarian stimulation protocols. The estimated health care expenditure for ART during 2017 was 101 278 629 888 JPY (920 714 817 USD), leading to a 0.24% increase in the national health care expenditure for fiscal year 2017. Fresh cycles accounted for 70% of the expenditure. The proportion of the average patient out-of-pocket payment for one treatment cycle was smaller for natural (0%) and mild ovarian stimulation using clomiphene citrate (4.5%-20.7%) than those of conventional stimulation (30.3%-32.4%). CONCLUSIONS: Health insurance coverage for ART would increase national health care expenditure by 0.24%. Under the subsidy system, the proportion of the average patient out-of-pocket payment was smaller for natural and mild ovarian stimulation than conventional stimulations.

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OBJECTIVE: This study aimed to compare the efficacy of physiological intracytoplasmic sperm injection (PICSI) and intracytoplasmic sperm injection (ICSI) in terms of the fertilization rate and embryo quality using sibling oocyte cycles. METHODS: This prospective, cross-sectional study collected data from 76 couples who underwent their first cycle at the Hue Center for Reproductive Endocrinology and Infertility, Vietnam, between May 2019 and November 2021. The inclusion criteria were cycles with at least eight oocytes and a sperm concentration of 5×106/mL. Sperm parameters, sperm DNA fragmentation (SDF), fertilization, and the quality of cleavage-stage embryos on day 2 and blastocysts on day 5 were examined. RESULTS: From 76 ICSI cycles, 1,196 metaphase II (MII) oocytes were retrieved, half of which were randomly allocated to either the PICSI (n=592) or ICSI (n=604) treatment group. The results showed no significant difference between the two groups in terms of fertilization (72.80% vs. 75.33%, p=0.32), day 2 cleavage rate (95.13% vs. 96.04%, p=0.51), blastulation rate (52.68% vs. 57.89%), and high-quality blastocyst rate (26.10% vs. 31.13%, p=0.13). However, in cases where SDF was low, 59 cycles consisting of 913 MII oocytes produced a considerably higher blastulation rate with PICSI than with ICSI (50.49% vs. 35.65%, p=0.00). There were no significant differences between the pregnancy outcomes of the PICSI and ICSI embryo groups following embryo transfer. CONCLUSION: Using variable sperm quality provided no benefit for PICSI versus ICSI in terms of embryo outcomes. When SDF is low, PICSI appears to be able to produce more blastocysts.

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Purpose: Since 1986, the Japan Society of Obstetrics and Gynecology assisted reproductive technology (ART) registry system has collected data on national ART use and outcomes trends in Japan. Herein, we describe the characteristics and outcomes of ART cycles registered during 2020 and compare the results with those from 2019. Methods and Results: In 2020, 621 ART facilities participated in the registration. The total number of registered cycles was 449 900, and there were 60 381 live births, which decreased from the previous year (1.79% and 0.36% decrease, respectively). The number of freeze-all in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles increased in 2020, and the number of neonates born was 2282 for IVF-embryo transfer (ET) cycles and 2596 for ICSI cycles, which had decreased from the previous year. Frozen-thawed ET (FET) cycles had slightly increased from 2019 (0.04%). In 2020, 215 285 FET cycles were conducted, resulting in 76 196 pregnancies and 55 503 neonates. Single ET was performed in 81.6% of fresh transfers and 85.1% of frozen-thawed cycles, respectively, resulting in over 97% singleton pregnancies/livebirths rates. Conclusion: Despite the COVID-19 pandemic during 2020, the overall number of ART cycles and neonates born demonstrated only a slight decrease in 2020 compared with 2019.

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PURPOSE: This study evaluated the predictors of sperm retrieval (SR) in non-mosaic Klinefelter syndrome (KS) patients undergoing microsurgical testicular sperm extraction (mTESE). The cutoff values of the predictors of SR and overall pregnancy rates after intracytoplasmic sperm injection (ICSI) were analyzed for the positive SR (PSR) cases. MATERIALS AND METHODS: The study was a dual-center retrospective study. Overall 118 patients with KS underwent mTESE between January 2011 and July 2021. Clinicopathological factors including comorbidities, endocrine profiles, and testicular volumes were analyzed. RESULTS: A total of 58 patients showed PSR (49.2%) and 60 patients (50.8%) had negative SR (NSR). The mean overall age of the patients was 32.5 years. The NSR patients had a significantly greater prevalence of obesity, diabetes mellitus, and cerebrovascular disease. The PSR group had a significantly higher left testis mean volume (p=0.039). The differences between the two study groups regarding follicular-stimulating hormone, luteinizing hormone, and testosterone variations at 1 and 3 months after mTESE were insignificant. Preoperative mean neutrophil-to-lymphocyte ratio was significantly greater in the NSR group (p=0.011), but the platelet-to-lymphocyte ratio showed no significant difference between the two study groups. A live child birth was achieved in 53.4% of the PSR patients. Multivariate logistic analysis showed that total testicular volume >3.93 mL, left testis volume >1.79 mL, and neutrophil-to-lymphocyte ratio ≤1.82 were significantly associated with PSR. CONCLUSIONS: mTESE-ICSI is a feasible method for KS patients to have a child, and total testicular volume, left testis volume, and neutrophil-to-lymphocyte ratio might be predictors of successful SR.

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Purpose: Relugolix is an oral gonadotropin-releasing hormone antagonist (GnRHant), which was first introduced in 2019. This study investigated the effects of the conventional injectable GnRHant formulation and this new oral GnRHant formulation on controlled ovarian stimulation (COS) cycles. Methods: Relugolix was administered in 126 cycles and conventional GnRHant injection was administered in 658 cycles (controls). The follicle stimulation was performed by an antagonist method, and for final oocyte maturation, recombinant human chorionic gonadotropin (rHCG), or gonadotropin-releasing hormone agonist (GnRHa), or both (dual trigger) were selected. The number of retrieved oocytes was counted and then they were evaluated for subsequent development up to cleavage stage. Results: The number of retrieved oocytes which was the primary outcome of this research was affected by the combination of GnRHant type and the final oocyte maturation agent. The combination of relugolix and a GnRHa trigger showed a significantly lower number of retrieved oocytes (p < 0.001) than the other combinations. Conclusions: Relugolix is a new option for COS cycles, but should be carefully combined with the final maturation agent. Clinical trial approval: This study was conducted after approval by the Medical Corporation Sankeikai Institutional Ethics Committee (approval number: 2019-34).

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Purpose: The Japan Society of Obstetrics and Gynecology records online annual cycle-based information for assisted reproductive technology (ART). This report presents the characteristics and treatment outcomes of ART cycles registered during 2019. Methods: The Japanese ART registry includes cycle-specific information from 619 participating facilities, including treatment and pregnancy outcomes. Descriptive analyses were conducted for cycles registered during 2019. Results: In 2019, 458 101 treatment cycles and 60 598 neonates were reported, both of which increased from 2018. The number of fresh cycles, including in vitro fertilization and intracytoplasmic sperm injection, decreased, while frozen-thawed embryo transfer (ET) cycles increased. The mean maternal age was 37.9 years (standard deviation ± 4.7). Of 239 348 oocyte retrievals, 123 690 (51.7%) involved freeze-all-embryos cycles; fresh ET was performed in 41 831 cycles (a decreasing trend since 2015). In 2019, there were 211 597 frozen-thawed ET cycles, resulting in 74 882 pregnancies and 54 168 neonates born. Single ET was performed in 82.6% of fresh transfers and 85.1% of frozen-thawed cycles, with singleton live birth rates of 97.3% for both. Conclusions: The number of fresh cycles decreased but frozen cycles increased in 2019. Single ET was performed in >80% of cases, and the proportion of babies born from frozen-thawed ET increased.

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BACKGROUND: The outcomes of the use of commercial in vitro maturation (IVM) medium to culture immature oocytes obtained from conventional ovulation induction, followed by rescue intracytoplasmic sperm injection (RICSI), are not ideal. It is thus difficult to widely adopt this approach in clinical practice. Therefore, it is necessary to explore methods for improving the clinical outcome of IVM. AIM: To study the effect of sperm on the developmental potential of in vitro-matured oocytes in conventional culture. METHODS: This was a retrospective study of patients whose immature oocytes were harvested from conventional oocyte stimulation cycles and underwent ICSI at our hospital between June 2018 and August 2020. RICSI was performed using sperm collected on the day of oocyte harvest (old) and sperm collected on the day of RICSI (fresh) and oocytes matured in vitro after 24 h of culture in conventional medium. The rates of in vitro oocyte maturation, normal fertilization, normal cleavage, day-3 top-quality embryos, and useful blastocyst formation were compared between the two groups. RESULTS: In total, 102 germinal vesicle (GV)-stage immature oocytes were cultured in the old sperm group. In the fresh sperm group, 122 GV-stage immature oocytes were collected and cultured in vitro for 24 h. There were no significant differences in the general conditions of males and females between the two groups (P > 0.05). The oocyte maturation, normal fertilization, and normal cleavage rates of the old and fresh groups were 51.0% vs 55.7%, 61.5% vs 64.7%, and 93.8% vs 93.2%, respectively. None of the rates differed significantly (P > 0.05) between the two groups. However, the day-3 top-quality embryo and useful blastocyst rates of the old and fresh sperm groups were 16.6% vs 63.4%; 6.67% vs 34.6%, respectively. The day-3 top-quality embryos and useful blastocyst rates of the old sperm group were significantly lower than those of the fresh group (P < 0.05). CONCLUSION: In vitro maturation with conventional culture medium combined with the use of fresh sperm collected on the day of RICSI is an easy-to-implement strategy for patients whose oocytes are completely or mostly immature.

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BACKGROUND: Despite all research efforts during this era of novel time-lapse morphokinetic parameters, a morphological grading system is still routinely being used for embryo selection at the blastocyst stage. The blastocyst expansion grade, as evaluated during morphological assessment, is associated with clinical pregnancy. However, this assessment is performed without taking the dynamics of blastocoel expansion into account. Here, we studied the dynamics of blastocoel expansion by comparing longitudinal blastocoel surface measurements using time-lapse embryo culture. Our aim was to first assess if this is impacted by fertilization method and second, to study if an association exists between these measurement and ongoing pregnancy. METHODS: This was a retrospective cohort study including 225 couples undergoing 225 cycles of in vitro fertilization (IVF) treatment with time-lapse embryo culture. The fertilization method was either conventional IVF, intracytoplasmic sperm injection (ICSI) with ejaculated sperm or ICSI with sperm derived from testicular sperm extraction (TESE-ICSI). This resulted in 289 IVF embryos, 218 ICSI embryos and 259 TESE-ICSI embryos that reached at least the full blastocyst stage. Blastocoel surface measurements were performed on time-lapse images every hour, starting from full blastocyst formation (tB). Linear mixed model analysis was performed to study the association between blastocoel expansion, the calculated expansion rate (µm2/hour) and both fertilization method and ongoing pregnancy. RESULTS: The blastocoel of both ICSI embryos and TESE-ICSI embryos was significantly smaller than the blastocoel of IVF embryos (beta -1121.6 µm2; 95% CI: -1606.1 to -637.1, beta -646.8 µm2; 95% CI: -1118.7 to 174.8, respectively). Still, the blastocoel of transferred embryos resulting in an ongoing pregnancy was significantly larger (beta 795.4 µm2; 95% CI: 15.4 to 1575.4) and expanded significantly faster (beta 100.9 µm2/hour; 95% CI: 5.7 to 196.2) than the blastocoel of transferred embryos that did not, regardless of the fertilization method. CONCLUSION: Longitudinal blastocyst surface measurements and expansion rates are promising non-invasive quantitative markers that can aid embryo selection for transfer and cryopreservation. TRIAL REGISTRATION: Our study is a retrospective observational study, therefore trial registration is not applicable.

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AIMS: To evaluate the results of microdissection testicular sperm extraction (micro-TESE) and intracytoplasmic sperm injection (ICSI) for treatment of non-obstructive azoospermia (NOA). MATERIALS AND METHODS: We retrospectively analysed data of 88 consecutive patients with clinical NOA who were treated with micro-TESE by a single surgeon, between August 2014 and September 2020, in Melbourne, Victoria. Upon a successful sperm retrieval, sperm was either used fresh for ICSI, frozen for future use or both. The outcome measures were sperm retrieval rate (SRR), and in vitro fertilisation (IVF)/ICSI results. Furthermore, SRR was calculated for the predominant causes and histopathological patterns. RESULTS: The overall SRR was 61.2%. It was significantly higher in patients with a history of cryptorchidism and other childhood diseases (100%) than in the other NOA groups (P < 0.05). Patients with Klinefelter syndrome had a 75% SRR. Among the different types of testicular histology, the highest SRR were noted in patients with complete hyalinisation (100%) and hypospermatogenesis (92.9%), and low with Sertoli cell-only syndrome (46.3%). The SRR has significantly increased from 33.3% in 2015-2016 to 73.6% in 2019-2020 (P = 0.009). Of the 52 patients with SSR, 47 underwent IVF/ICSI. Fertilisation rate was 42.4%. Twenty-nine couples achieved at least one good-quality embryo and had embryo transfer. Nineteen achieved pregnancy (40.4%), and in three patients a miscarriage resulted. CONCLUSIONS: This is the first report from Australia showing that micro-TESE is an effective treatment for NOA with high SRR. The increasing success rates over several years indicate the importance of surgical skill and laboratory staff experience.

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BACKGROUND: In vitro fertilisation is a widely used reproductive technique that can be undertaken with or without intracytoplasmic sperm injection. The endometrial scratch procedure is an in vitro fertilisation 'add-on' that is sometimes provided prior to the first in vitro fertilisation cycle, but there is a lack of evidence to support its use. OBJECTIVES: (1) To assess the clinical effectiveness, safety and cost-effectiveness of endometrial scratch compared with treatment as usual in women undergoing their first in vitro fertilisation cycle (the 'Endometrial Scratch Trial') and (2) to undertake a systematic review to combine the results of the Endometrial Scratch Trial with those of previous trials in which endometrial scratch was provided prior to the first in vitro fertilisation cycle. DESIGN: A pragmatic, multicentre, superiority, open-label, parallel-group, individually randomised controlled trial. Participants were randomised (1 : 1) via a web-based system to receive endometrial scratch or treatment as usual using stratified block randomisation. The systematic review involved searching electronic databases (undertaken in January 2020) and clinicaltrials.gov (undertaken in September 2020) for relevant trials. SETTING: Sixteen UK fertility units. PARTICIPANTS: Women aged 18-37 years, inclusive, undergoing their first in vitro fertilisation cycle. The exclusion criteria included severe endometriosis, body mass index ≥ 35 kg/m2 and previous trauma to the endometrium. INTERVENTIONS: Endometrial scratch was undertaken in the mid-luteal phase of the menstrual cycle prior to in vitro fertilisation, and involved inserting a pipelle into the cavity of the uterus and rotating and withdrawing it three or four times. The endometrial scratch group then received usual in vitro fertilisation treatment. The treatment-as-usual group received usual in vitro fertilisation only. MAIN OUTCOME MEASURES: The primary outcome was live birth after completion of 24 weeks' gestation within 10.5 months of egg collection. Secondary outcomes included implantation, pregnancy, ectopic pregnancy, miscarriage, pain and tolerability of the procedure, adverse events and treatment costs. RESULTS: One thousand and forty-eight (30.3%) women were randomised to treatment as usual (n = 525) or endometrial scratch (n = 523) and were followed up between July 2016 and October 2019 and included in the intention-to-treat analysis. In the endometrial scratch group, 453 (86.6%) women received the endometrial scratch procedure. A total of 494 (94.1%) women in the treatment-as-usual group and 497 (95.0%) women in the endometrial scratch group underwent in vitro fertilisation. The live birth rate was 37.1% (195/525) in the treatment-as-usual group and 38.6% (202/523) in the endometrial scratch group: an unadjusted absolute difference of 1.5% (95% confidence interval -4.4% to 7.4%; p = 0.621). There were no statistically significant differences in secondary outcomes. Safety events were comparable across groups. No neonatal deaths were recorded. The cost per successful live birth was £11.90 per woman (95% confidence interval -£134 to £127). The pooled results of this trial and of eight similar trials found no evidence of a significant effect of endometrial scratch in increasing live birth rate (odds ratio 1.03, 95% confidence interval 0.87 to 1.22). LIMITATIONS: A sham endometrial scratch procedure was not undertaken, but it is unlikely that doing so would have influenced the results, as objective fertility outcomes were used. A total of 9.2% of women randomised to receive endometrial scratch did not undergo the procedure, which may have slightly diluted the treatment effect. CONCLUSIONS: We found no evidence to support the theory that performing endometrial scratch in the mid-luteal phase in women undergoing their first in vitro fertilisation cycle significantly improves live birth rate, although the procedure was well tolerated and safe. We recommend that endometrial scratch is not undertaken in this population. TRIAL REGISTRATION: This trial is registered as ISRCTN23800982. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 10. See the NIHR Journals Library website for further project information.

The endometrial scratch is a simple procedure that involves 'scratching' the lining of the womb (the endometrium). Several small studies have shown that undertaking this before the first in vitro fertilisation cycle may improve live birth rates; however, other studies have contradicted this. This large study was carried out to confirm whether or not having an endometrial scratch before the first in vitro fertilisation cycle would increase the number of women having a live birth compared with those having 'usual' in vitro fertilisation treatment (known as the 'control' group). We collected information about pregnancy, miscarriage, stillbirth, pain during the procedure and costs of treatment to find out if there were any meaningful differences. A total of 1048 women aged between 18 and 37 years were randomly allocated to the two groups, so participants had a 50% chance of having the endometrial scratch. Women were followed up throughout their pregnancy to ascertain the outcome of their in vitro fertilisation cycle. Although the live birth rate was 1.5% higher in the endometrial scratch group (38.6%) than in the control group (37.1%), the difference was not large enough to show any benefit of having the procedure. Other outcomes did not differ significantly between the two groups. However, the procedure was safe and tolerable. We found that the cost of treatment was, on average, £316 per participant higher in the group that received endometrial scratch than in the control group; the difference was not large enough to show that receiving endometrial scratch was more cost-effective. We combined the results of this trial with those of previous trials that looked to answer a similar question, and found that, overall, the endometrial scratch procedure does not enhance the chances of achieving a live birth. We conclude that endometrial scratch before first-time in vitro fertilisation does not improve the outcome of treatment, and we recommend that this procedure is not undertaken prior to a first cycle of in vitro fertilisation.

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Objective:To explore the effect of dyslipidemia on the clinical outcome of intracytoplasmic sperm injection-embryo transfer (ICSI-ET) in infertility patients receiving donor eggs.Methods:A total of 118 patients were selected to receive egg donors and ICSI-ET at the First Affiliated Hospital of Nanjing Medical University between April 2007 and December 2020. According to the levels of triacylglycerol, serum cholesterol, high density lipoprotein (HDL), and low density lipoprotein, they were divided into dyslipidemia group (35 cases) and normal blood lipids group (83 cases). The influence of body mass index (BMI) and age was adjusted by 1∶1 propensity score matching, and the general condition and clinical outcome of the two groups were analyzed retrospectively. Finally, the relationship between lipid composition and clinical outcome was analyzed according to patients′ age and BMI.Results:(1) Comparing the pre-matching dyslipidemia group with the normal blood lipids group, the BMI of the dyslipidemia group was significantly higher than that of the normal blood lipids group [(23.5±2.4) vs (22.4±2.7) kg/m 2], and the embryo implantation rate was significantly lower than that of the normal blood lipids group [13.6% (8/59) vs 27.3% (36/132)], the differences were statistically significant (both P<0.05). (2) There were no significant differences in years of infertility, number of pregnancies, number of abortions, number of transplanted embryos, protocol of endometrial preparation, endometrial thickness on transplantation day and high quality embryo rate between the two groups, through propensity score matching (all P>0.05). The biochemical pregnancy rate [28.6% (10/35)], embryo implantation rate [13.6% (8/59)] and live birth rate [20.0% (7/35)] in dyslipidemia group were significantly lower than those in the normal blood lipids group ( P<0.05). The clinical pregnancy rate was lower than that of the normal blood lipids group ( P>0.05). (3) The results of stratified analysis showed that the level of HDL in the clinically non-pregnant group was significantly lower than that in the pregnant group in patients ≤ 35 years old [(1.5±0.3) vs (1.8±0.5) mmol/L; P<0.05]. In the overweight recipient patients, the level of HDL of the clinically non-pregnant group was lower than that of the pregnant group ( P>0.05). Conclusions:Dyslipidemia significantly reduces the biochemical pregnancy rate, embryo implantation rate and live birth rate in patients with receiving donor eggs. Especially in patients aged ≤35 years old, the reduction of HDL is closely related to adverse pregnancy outcomes.

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Advanced reproductive technologies are being applied for the propagation of squirrel monkeys, to ensure their preservation as a genetic resource and the effective use of their gametes in the future. In the present study, oocytes and spermatozoa were collected from live squirrel monkeys, following which piezo intracytoplasmic sperm injection (ICSI) was performed using these gametes. Follicular development was induced by administering equine chorionic gonadotropin (eCG) containing inhibin antiserum to an immature squirrel monkey female. The unilateral ovary was excised after the administration of human chorionic gonadotropin (hCG), to induce ovulation, following which the larger developed follicular oocytes were collected. Follicular oocytes were prepared for ICSI using sperm from the epididymal tail of a unilateral testis extracted from a mature male. The embryos were continuously incubated in CMRL 1066 medium supplemented with 10% (v/v) fetal bovine serum. Embryo culture was performed with cumulus cells. Two experiments of ICSI carried out with three females resulted in 14 mature oocytes from the 49 cumulus-oocyte complexes collected and five embryos, three of which developed into blastocysts. These blastocysts were vitrified, thawed, and transferred to recipient monkeys, but no pregnancies resulted. In conclusion, the present study is the first to successfully produce ICSI-derived blastocysts from MII oocytes obtained by means of hormone administration (a combination of eCG+inhibin antiserum and hCG) and in vitro maturation in immature squirrel monkeys.

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