Prediction of Reproductive Outcomes of Intracytoplasmic Sperm Injection Cycles Using a Multivariate Scoring System.

Background: Prediction of in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) success is crucial in counselling patients about their real chance of getting a live birth before commencing treatment. A multivariate scoring system proposed by Younis et al., 2010, was amongst the predictive models used to evaluate IVF/ICSI success. The score entitles basal endocrine, clinical and sonographic parameters. Aims: The objective of this study is to assess the predictability of the Younis multivariate score for pregnancy outcomes in ICSI cycles. Settings and Design: This prospective observational cohort study (NCT03846388) included patients who pursued IVF or ICSI in a tertiary infertility unit between February 2019 and December 2021. Materials and Methods: The score variables were age, body mass index, antral follicle count, basal follicle-stimulating hormone (FSH), basal FSH/luteinising hormone ratio, infertility duration, number of previous cancellations and mean ovarian volume. For each woman included in the study, Younis multivariate score was calculated. Then, we correlate the different reproductive outcomes with score levels to validate the score predictability. A score of ≤14 was defined as a low score based on the previous study's results. Statistical Analysis Used: The student's t-test and Mann-Whitney test were used to compare numerical variables, whereas categorical variables were analysed using the Chi-square test. A receiver operating curve (ROC) and a multivariate logistic regression model were used to investigate the predictability of the Younis scoring model for cycle outcomes. Results: Two hundred ninety-two ICSI-ET cycles were analysed. Of the total cohort, 143 (48.97%) women included showed a low score (≤14), whereas 149 (51.03%) women showed a high score (>14). Women with low scores had significantly higher pregnancy and live birth rates compared to women with high scores (60.1% vs. 7.4%, respectively, P < 0.001; 44.7% vs. 6.7%, respectively, P < 0.001). The area under the curve (AUC) in the ROC curve analysis showed a higher predictability for the scoring system for live birth rate with an AUC of 0.796, with a sensitivity of 86.5% and specificity of 63.8% when using a cut-off level of ≤14. For pregnancy prediction, the AUC was 0.829, with a sensitivity of 88.66% and a specificity of 70.77% when using the same cut-off. Women who have a low score have a high chance of having frozen embryos. Likewise, women who have a high score have a very high chance of cycle cancellation. Conclusions: The Younis multivariate score can be used for the prediction of ICSI cycle outcomes and to calculate the chance of cycle cancellation, pregnancy and take-home baby before ICSI.

Genetic Counseling for an Infertile Couple With Premature Chromatid Separation (PCS) Syndrome: A Case Report.

We report the first case of successful genetic counseling for an infertile couple with premature chromatid separation (PCS) syndrome. After our careful genetic counseling, the couple decided to continue infertility treatment. As a result, they gave birth to a baby (girl: 2,930 g) by caesarean section in May 2018. To our knowledge, there have not been any published reports regarding genetic counseling for an infertile couple with PCS after PubMed, EMBASE, and Web of Science searches until March 2024.

High estradiol levels in fresh embryo transfer cycles are not associated with detrimental impact on birth outcomes.

PURPOSE: There is an unclear relationship between estradiol levels and fresh embryo transfer (ET) outcomes. We determined the relationship between estradiol on the day of trigger, in fresh ET cycles without premature progesterone elevation, and good birth outcomes (GBO). METHODS: We identified autologous fresh ET cycles from 2015 to 2021 at multiple clinics in the USA. Patients with recurrent pregnancy loss, uterine factor, and elevated progesterone on the day of trigger (progesterone > 2 ng/mL or 3-day area under the curve > 4.5 ng/mL) were excluded. The primary outcome was GBO (singleton, term, live birth with appropriate weight). Log-binomial generalized estimating equations determined the likelihood of outcomes. RESULTS: Of 17,608 fresh ET cycles, 5025 (29%) yielded GBO. Cycles with estradiol ≥ 4000 pg/mL had a greater likelihood of GBO compared to cycles < 1000 pg/mL (aRR = 1.32, 95% CI 1.13-1.54). Pairwise comparisons of estradiol between < 1000 pg/mL versus 1000-1999 pg/mL and 1000-1999 pg/mL versus 2000-2999 pg/mL revealed a higher likelihood of GBO with higher estradiol (aRR 0.83, 95% CI 0.73-0.95; aRR 0.91, 95% CI 0.85-0.97, respectively). Comparisons amongst more elevated estradiol levels revealed that the likelihood of GBO remained similar between groups (2000-2999 pg/mL versus 3000-3999 pg/mL, aRR 1.04, 95% CI 0.97-1.11; 3000-3999 pg/mL versus ≥ 4000 pg/mL, aRR 0.96, 95% CI 0.9-1.04). CONCLUSION: In fresh ET cycles, higher estradiol levels were associated with an increased prevalence of GBO until estradiol 2000-2999 pg/mL, thereafter plateauing. In fresh ET candidates, elevated estradiol levels should not preclude eligibility though premature progesterone rise, and risk of ovarian hyperstimulation syndrome must still be considered.

Effect of Day 3 cell number on the live birth rate of vitrified-warmed Day 5 single blastocyst transfer in young women.

BACKGROUND: Previous studies have reported inconsistent results regarding blastocyst selection with a high day 3 (D3) cell number and the eventual pregnancy outcomes. Thus, in this study, the relationship between the D3 cell number and clinical outcomes of day 5 single blastocyst transfer (SBT) in vitrified-warmed transfer cycles was investigated. METHODS: Our retrospective study included 1144 day 5 SBT in vitrified-warmed cycles between February 2016 and February 2021. All cycles were the first vitrified-warmed cycles, and the female patients were less than 35 years of age. Based on the D3 cell number, the cycles were divided into four groups, as follows: group A (3-7 cells, n = 130); group B (8-9 cells, n = 621); group C (10-12 cells, n = 328); and group D (13-16 cells, n = 65). The differences in the live birth rate (LBR), clinical pregnancy rate, and miscarriage rate were examined among the four groups. RESULTS: The LBR and clinical pregnancy rate increased with the D3 cell number (P < 0.01). No significant difference was found in the miscarriage rate among the groups (P = 0.055). After adjusting for confounding factors, the LBR was significantly higher in groups C (odds ratio [OR] = 1.477, 95% confidence interval [CI]: 1.124-1.941, P = 0.005) and D (OR = 2.000, 95% CI: 1.166-3.429, P = 0.012) than in group B. CONCLUSIONS: A high D3 cell number (> 9 cells) was associated with a high LBR in the vitrified-warmed day 5 SBT cycles of patients < 35 years of age. The cell number of D3 embryos can be an important reference indicator for blastocyst selection. Among blastocysts with the same morphological score, those with > 9 cells on D3 can be preferentially selected for transplantation.

Can serum progesterone concentration direct a fresh or freeze-all transfer strategy in the first in vitro fertilisation cycle?

PURPOSE: To examine the interaction between serum progesterone concentration on the trigger day and choice of freeze-all and fresh transfer strategies on live birth in an unselected population as well as in patients over 35 years old. METHODS: We performed a retrospective cohort study of 26,661 patients commencing their first IVF cycle in a large fertility centre between 2015 and 2019, including 4687 patients over 35 years old. We performed a multivariable fractional polynomial interaction analysis within a logistic regression model to investigate the interaction between serum progesterone concentration and the choice of freeze-all or fresh transfer strategy following the first transfer. RESULTS: 15,539 patients underwent a fresh embryo transfer and 11,122 underwent a freeze-all strategy in their first IVF cycle. The freeze-all group had a higher live birth rate compared to the fresh group (43.9% vs 40.3%). After adjusting for confounding factors, there was a positive interaction between serum progesterone concentrations and the choice of a freeze-all versus fresh embryo transfer on live birth (p for interaction 0.0001), with a larger magnitude of effect when progesterone concentration was higher. Such an interaction was also observed in patients over 35 years old (p for interaction 0.01), but the treatment effect curve over progesterone concentrations was almost flat. CONCLUSIONS: In an unselected population, frozen transfer is associated with greater chances of live birth, especially in patients with higher serum progesterone concentration. In patients over 35 years old, the benefit of a freeze-all policy appears small across all serum progesterone concentrations.

Impact of thyroid autoimmunity on the cumulative live birth rates after IVF/ICSI treatment cycles.

BACKGROUND: Cumulative live birth rate (CLBR) is considered as the most important endpoint for assessing the probability of having a baby in a complete in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment cycle. Many previous studies have focused on the association between thyroid autoimmunity (TAI) and live birth rate after first embryo transfer cycle, however, evidence on whether the presence of TAI affects the CLBR is lacking. The purpose of this study is to investigate the impact of TAI on the CLBR in a complete IVF/ICSI cycle. METHODS: This retrospective study included 12,796 women who underwent their first IVF/ICSI treatment between January 2019 and February 2021. Based on the levels of thyroid antibodies, 2,603 women were assigned to the TAI group, and 10,193 women were assigned to the control group. Subgroup analysis was performed according to the different causes of infertility (including male factor only, ovulation disorder, tubal factor, endometriosis and unexplained infertility) and different types and titres of thyroid antibodies. The primary outcome in this study was CLBR, which included live births from the fresh embryo transfer cycle and all subsequent frozen-thawed embryo transfer cycles performed before December 2021. RESULTS: There was no significant difference in the CLBR between the TAI and control groups, even after adjusting for relevant confounders including age, body mass index, cause of infertility, thyroid function, protocols of controlled ovarian stimulation, type of transfer (fresh vs. frozen), type of transferred embryo (cleavage-stage embryo vs. blastocyst), and fertilization method (IVF vs. ICSI) (cumulative live birth: 50.6% vs. 52.1%, OR 0.94, 95% CI 0.86-1.02, adjusted OR 0.97, 95%CI 0.89-1.06). Subgroup analysis showed that no significant difference was observed in CLBR between the TAI and control groups for all causes of infertility, except for infertility attributed to endometriosis. Among women with endometriosis, the CLBR was significantly lower in the TAI group than that in the control group; however, this difference was not significant after adjusting for potential confounders including age, body mass index, thyroid function, protocols of controlled ovarian stimulation, type of transfer (fresh vs. frozen), type of transferred embryo (cleavage-stage embryo vs. blastocyst), and fertilization method (IVF vs. ICSI) (cumulative live births: 43.1% vs. 51.0%, OR 0.73, 95% CI 0.53-0.99, adjusted OR 0.74, 95% CI 0.53-1.02). Another subgroup analysis demonstrated that the type and titre of thyroid antibody did not affect CLBR in women with TAI. CONCLUSIONS: In our study, there was no significant difference in the CLBR between women with TAI and those without TAI, which suggests that TAI did not affect the chances of having a baby in a complete IVF/ICSI treatment cycle.

[Live birth rates after breast cancer among women who desired a child]. / Naissances vivantes après cancer du sein parmi les femmes désirant un enfant.

INTRODUCTION: In France, the breast cancer is the most common cancer among women under the age of 40. From 38 to 70% of women have not fulfilled their parental plans at the time of diagnosis. The gonadotoxicity of the treatments and the follicular physiological decline linked to age can become an obstacle to this project. METHODS: Among the patients, 386 were treated for breast cancer at the Centre Georges-François-Leclerc in Dijon between January 2011 and December 2018 were identified. 192 patients aged under 39 met the inclusion criteria. We excluded metastatic cancers, cancer in situ and pregnant patients at diagnosis. A total of 124 patients agreed to participate in the study. The included patients filled out a self-questionnaire. Data were collected from the patient's electronic medical. The primary endpoint of this study was the live birth rate. RESULT: Among women who desired a child after breast cancer, the overall rate of live births was 36.2 % (21/58). Most achieved pregnancies were spontaneous (90.5 %). No factor was significantly associated with the absence of obtaining birth. Fertility was preserved by oocyte cryopreservation in 13.8 % of patients (17/124). The median time to conception in patients who received chemotherapy was 8 months [1.0-60.0] vs 2 months [1.0-7.0] in women who did not receive chemotherapy. DISCUSSION: The non-negligible proportion of live births following spontaneous pregnancy after breast cancer allows us to be reassuring for patients. However, the emergence of new chemotherapy protocols whose consequences on long-term gonadotoxicity are still not well known requires further studies and prompts the promotion of fertility preservation as a precautionary measure.

The utility of human two plus one small pronucleated zygotes (2.1PN) based on clinical outcomes and the focused ploidy analysis.

PURPOSE: Are human embryos arising from two plus one small pronucleated zygotes, called 2.1 pronuclei (PN), clinically useful? METHODS: In a retrospective embryo cohort study and prospective experimental study, a total of 287 cycles in which at least one 2.1PN was identified in the fertilization check were included. Embryonic development and clinical outcome were compared for the 1395 2PN zygotes and 304 2.1PN zygotes that were siblings. All embryos were individually cultured in time-lapse systems. Twenty-five 2.1PN-derived blastocysts, donated for research, were used in focused single-nucleotide variant ploidy analysis to identify the distribution pattern of heterozygosity. RESULTS: The average diameter of PN was 24.9 ± 2.4 µm for large PN and 10.2 ± 2.4 µm for small PN; 79.9% of small PN was derived from female pronuclei. Blastocyst formation rate and good-quality blastocyst rate were significantly lower with 2.1PN embryos than with 2PN embryos (40.0% vs. 57.7%, 21.4% vs. 33.5%, respectively). A total of 13 embryos derived from 2.1PN were transferred, and three healthy babies were born. In ploidy constitutions of trophectoderm (TE), 2.1PN-derived blastocyst TE was shown to be mostly diploid (95.8%, 23/24), and only one blastocyst showed triploid. CONCLUSIONS: It was suggested that 2.1PN embryos have lower embryonic developmental potential than 2PN embryos, but most of the 2.1PN were diploid, indicating that they are likely to be clinically usable. It is recommended to perform embryo transfer following a combination of PGT-A and ploidy analysis.

Age-related increase in live-birth rates of first frozen thaw embryo versus first fresh transfer in initial assisted reproductive technology cycles without PGT.

BACKGROUND: The landscape of assisted reproductive technology (ART) has seen a significant shift towards frozen-thawed embryo transfers (FET) over fresh transfers, driven by technological advancements and clinical considerations. This study aimed to compare live birth outcomes between primary FET and fresh transfers, focusing on cycles without preimplantation genetic testing (PGT), using United States national data from the SART CORS database spanning from 2014 to 2020. METHODS: We performed a retrospective cohort study of autologous first ART cycles without PGT comparing primary embryo transfer (frozen thaw vs. fresh) success rates from the 2014-2020 SARTCORS database. Live-birth rates (LBR) and cumulative live-birth rates (CLBR) were compared between first FET versus first fresh embryo transfer from an index retrieval. Multivariate logistic regression (MLR) determined association between live birth outcomes and method of transfer. In a subsequent sub-analysis, we compared these two embryo transfer methods among patients with either diminished ovarian reserve (DOR) or male factor infertility. RESULTS: 228,171 first ART cycles resulted in primary embryo transfer. 62,100 initial FETs and 166,071 fresh transfers were compared. Initial FETs demonstrated higher LBR and CLBR compared to fresh transfers (LBR 48.3% vs. 39.8%, p < 0.001; CLBR 74.0% vs. 60.0%, p < 0.0001). MLR indicated greater chances of live birth with FET across all age groups, with adjusted odds ratio (aOR) of live-birth incrementally increasing with advancing age groups. For DOR cycles, LBR and CLBR were significantly higher for FET compared to fresh (33.9% vs. 26.0%, p < 0.001, 44.5% vs. 37.6%, p < 0.0001), respectively. MF cycles also demonstrated higher LBR and CLBR with FET (52.3% vs. 44.2%, p < 0.001, 81.2% vs. 68.9%, p < 0.0001), respectively. MLR demonstrated that in DOR cycles, initial FET was associated with greater chance of live birth in age groups ≥ 35yo (p < 0.01), with aOR of live birth increasingly considerably for those > 42yo (aOR 2.63, p < 0.0001). CONCLUSIONS: Overall LBR and CLBR were greater for first FET than fresh transfers with incremental increases in odds of live birth with advancing age, suggesting the presence of a more favorable age-related change in endometrial receptivity present in frozen-thawed cycles. For both DOR and MF cycles, LBR and CLBR after primary transfer were greater for first FET than fresh. However, this was particularly evident in older ages for DOR cycles. This suggests that supraphysiologic stimulation in older DOR cycles may be detrimental to endometrial receptivity, which is in part corrected for in FET cycles.

Impact of dehydroepiandrosterone sulfate and free androgen index on pregnancy and neonatal outcomes in PCOS patients.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder associated with infertility and pregnancy complications. The pathogenesis of PCOS and its impact on reproductive function may be influenced by the source of androgens, including testosterone, free androgen, dehydroepiandrosterone sulfate (DHEAS). However, the differential effects of these androgen on pregnancy and neonatal outcomes and the cut-off value of East Asian population with PCOS remain unclear. METHODS: A retrospective cohort study was conducted at the Reproductive Medicine Center of the First Affiliated Hospital of Sun Yat-sen University from January 2015 to November 2022, involving 636 cycles of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). Subgroup analyses were performed using cut-off values of 6.4 for free androgen index (FAI), 9.5 µmol/L for DHEAS. Pregnancy and neonatal outcomes were compared between groups. Restricted cubic spline (RCS) was used to identify significant cut-off values affecting pregnancy. RESULTS: Higher FAI levels (> 6.4) were associated with decrease in clinical pregnancy rate (PR) (50.61% vs. 41.66%, p = 0.024), live birth rate (LBR) (42.42% vs. 32.35%, p = 0.011). When DHEAS levels exceeded 9.5 µmol/L, there was a significant decrease in clinical PR (51.27% vs. 42.73%, P = 0.039), LBR (42.73% vs. 32.73%, P = 0.012). Negative correlations were also observed between DHEAS levels and cumulative pregnancy rate (70.57% vs 56.62% p = 0.002) and cumulative live birth rate (CLBR) (59.35% vs 43.37%, p = 0.0007). Both FAI and DHEAS elevated is associated with the lowest clinical pregnancy rate (37.84%). Conversely, when solely FAI is elevated, the pregnancy rate increases to 52.38%, while an elevation in DHEAS alone is associated with a pregnancy rate of, both of which are lower than when neither FAI nor DHEAS are elevated (60.68%). The live birth rates exhibit a similar trend (30.00% vs 40.00% vs 41.83% vs 44.48%). RCS revealed a significant decrease in CPR and CLBR when DHEA levels exceeded 7.69 umol/L, while the cut-off value of FAI was 6.36 for CPR and CLBR. CONCLUSION: In conclusion, PCOS patients with biochemical hyperandrogenism show unsatisfactory clinical PR and CLBR when undergoing assisted reproductive technology (ART). This may be attributed to the influence of both adrenal-derived DHEAS and ovarian-derived FAI on the unfavorable pregnancy outcomes.

Endometrial Receptivity Array (ERA) Test in a 32-Year-Old Female With Refractory Infertility: A Case Report.

We report a successful case for the clinical efficacy of the endometrial receptivity array (ERA) test for a 32-year-old female patient with refractory infertility. After our careful treatment, the patient gave birth to a male baby (3390 g) in November 2021. To our knowledge, though the clinical efficacy of the ERA test is controversial until March 2024, we think that the age of the patients, the number of IVF cycles, and the racial differences may have an impact on the clinical efficacy of the ERA test.

Hysterosalpingo-foam sonography versus hysterosalpingography during fertility work-up: an economic evaluation alongside a randomized controlled trial.

STUDY QUESTION: What are the costs and effects of tubal patency testing by hysterosalpingo-foam sonography (HyFoSy) compared to hysterosalpingography (HSG) in infertile women during the fertility work-up? SUMMARY ANSWER: During the fertility work-up, clinical management based on the test results of HyFoSy leads to slightly lower, though not statistically significant, live birth rates, at lower costs, compared to management based on HSG results. WHAT IS KNOWN ALREADY: Traditionally, tubal patency testing during the fertility work-up is performed by HSG. The FOAM trial, formally a non-inferiority study, showed that management decisions based on the results of HyFoSy resulted in a comparable live birth rate at 12 months compared to HSG (46% versus 47%; difference -1.2%, 95% CI: -3.4% to 1.5%; P = 0.27). Compared to HSG, HyFoSy is associated with significantly less pain, it lacks ionizing radiation and exposure to iodinated contrast medium. Moreover, HyFoSy can be performed by a gynaecologist during a one-stop fertility work-up. To our knowledge, the costs of both strategies have never been compared. STUDY DESIGN, SIZE, DURATION: We performed an economic evaluation alongside the FOAM trial, a randomized multicenter study conducted in the Netherlands. Participating infertile women underwent, both HyFoSy and HSG, in a randomized order. The results of both tests were compared and women with discordant test results were randomly allocated to management based on the results of one of the tests. The follow-up period was twelve months. PARTICIPANTS/MATERIALS, SETTING, METHODS: We studied 1160 infertile women (18-41 years) scheduled for tubal patency testing. The primary outcome was ongoing pregnancy leading to live birth. The economic evaluation compared costs and effects of management based on either test within 12 months. We calculated incremental cost-effectiveness ratios (ICERs): the difference in total costs and chance of live birth. Data were analyzed using the intention to treat principle. MAIN RESULTS AND THE ROLE OF CHANCE: Between May 2015 and January 2019, 1026 of the 1160 women underwent both tubal tests and had data available: 747 women with concordant results (48% live births), 136 with inconclusive results (40% live births), and 143 with discordant results (41% had a live birth after management based on HyFoSy results versus 49% with live birth after management based on HSG results). When comparing the two strategies-management based on HyfoSy results versus HSG results-the estimated chance of live birth was 46% after HyFoSy versus 47% after HSG (difference -1.2%; 95% CI: -3.4% to 1.5%). For the procedures itself, HyFoSy cost €136 and HSG €280. When costs of additional fertility treatments were incorporated, the mean total costs per couple were €3307 for the HyFoSy strategy and €3427 for the HSG strategy (mean difference €-119; 95% CI: €-125 to €-114). So, while HyFoSy led to lower costs per couple, live birth rates were also slightly lower. The ICER was €10 042, meaning that by using HyFoSy instead of HSG we would save €10 042 per each additional live birth lost. LIMITATIONS, REASONS FOR CAUTION: When interpreting the results of this study, it needs to be considered that there was a considerable uncertainty around the ICER, and that the direct fertility enhancing effect of both tubal patency tests was not incorporated as women underwent both tubal patency tests in this study. WIDER IMPLICATION OF THE FINDINGS: Compared to clinical management based on HSG results, management guided by HyFoSy leads to slightly lower live birth rates (though not statistically significant) at lower costs, less pain, without ionizing radiation and iodinated contrast exposure. Further research on the comparison of the direct fertility-enhancing effect of both tubal patency tests is needed. STUDY FUNDING/COMPETING INTEREST(S): FOAM trial was an investigator-initiated study, funded by ZonMw, a Dutch organization for Health Research and Development (project number 837001504). IQ Medical Ventures provided the ExEm®-FOAM kits free of charge. The funders had no role in study design, collection, analysis, and interpretation of the data. K.D. reports travel-and speakers fees from Guerbet and her department received research grants from Guerbet outside the submitted work. H.R.V. received consulting-and travel fee from Ferring. A.M.v.P. reports received consulting fee from DEKRA and fee for an expert meeting from Ferring, both outside the submitted work. C.H.d.K. received travel fee from Merck. F.J.M.B. received a grant from Merck and speakers fee from Besins Healthcare. F.J.M.B. is a member of the advisory board of Merck and Ferring. J.v.D. reported speakers fee from Ferring. J.S. reports a research agreement with Takeda and consultancy for Sanofi on MR of motility outside the submitted work. M.v.W. received a travel grant from Oxford Press in the role of deputy editor for Human Reproduction and participates in a DSMB as independent methodologist in obstetrics studies in which she has no other role. B.W.M. received an investigator grant from NHMRC GNT1176437. B.W.M. reports consultancy for ObsEva, Merck, Guerbet, iGenomix, and Merck KGaA and travel support from Merck KGaA. V.M. received research grants from Guerbet, Merck, and Ferring and travel and speakers fees from Guerbet. The other authors do not report conflicts of interest. TRIAL REGISTRATION NUMBER: International Clinical Trials Registry Platform No. NTR4746.

Cumulative live birth rates following intrauterine insemination using donor and husband sperm in different age groups: A cohort study of 10 415 insemination cycles.

OBJECTIVES: To assess the age-specific cumulative live birth rates (CLBRs) in intrauterine insemination (IUI) cycles using either donor or husband sperm, and to investigate the impact of sperm sources on IUI success among women within the same age group. METHODS: This retrospective cohort study comprised women who underwent IUI with donor sperm (IUI-D) or husband sperm (IUI-H) from 2017 to 2021. The women were stratified based on their age at the initiation of insemination into four categories: <35, 35-37, 38-39 and ≥40 years. RESULTS: A total of 5253 women undergoing 10 415 insemination cycles (3354 with IUI-D and 7061 with IUI-H) were included. The CLBRs decreased significantly with increasing maternal age within donor and husband insemination groups (P < 0.001). In the IUI-D group, the crude CLBRs were 61.50% in women aged <35, 48.91% in 35-37, 24.14% in 38-39 and 11.76% in the ≥40-year age category, respectively. The corresponding rates in the IUI-H group were 27.62%, 22.96%, 13.73% and 6.90%, respectively. Within the <35 and 35-37-year age categories, the CLBRs were significantly higher following IUI-D cycles compared to IUI-H cycles, with hazard ratios (HR) of 1.85 (1.68-2.04) and 1.69 (1.16-2.47), respectively. However, within the 38-39 and ≥40-year age categories, both IUI-D and IUI-H resulted in comparable low CLBRs, with HRs of 1.91 (0.77-4.76) and 1.80 (0.33-9.86), respectively. CONCLUSION: Advanced maternal age affects the whole process of fertility. Therefore, it could be reasonable to limit the number of IUI performed in women aged 40 years and older, even in couple using donor sperm for reproduction.

Live birth derived from a markedly large polar body oocyte: a rare case report.

Oocytes with excessively large first polar bodies (PB1) often occur in assisted reproductive procedures. Many times these oocytes are discarded without insemination and, as a result, the application of this portion of oocytes has scarcely been reported to date. Few studies have examined large PB1 oocytes in infertile women and have virtually entirely studied genetic variations for large PB1 oocyte abnormalities. Here, we describe an unusual case of a live birth from a remarkably large PB1 oocyte in a frozen embryo transfer (FET) cycle. This is the first instance of a successful live birth resulting from a PB1 oocyte with an extremely large polar body measuring 80 µM × 40 µM in size. The large PB1 oocyte was performed by an early rescue intracytoplasmic sperm injection (r-ICSI) and was formed into a blastocyst on day 5. Following FET, a healthy boy baby weighing 3100 g was finally delivered by caesarean section at 37 weeks and 5 days after conception. Additionally, there were no complications throughout the antenatal period or the perinatal phase of this following full-term delivery. In this study, it is revealed for the first time that a huge PB1 oocyte can be fertilized, resulting in the growth of a blastocyst, a subsequent pregnancy, and a live birth. This new information prompts us to reconsider the use of large PB1 oocytes. More insightful talks should be given attention to prevent the waste of embryos because not all oocytes with aberrant morphology are unavailable.

Effect of diminished ovarian reserve on the outcome of fresh embryo transfer in IVF/ICSI cycles among young women: A retrospective cohort study.

OBJECTIVE: This study aims to investigate the effect of diminished ovarian reserve (DOR) on the clinical outcomes and maternal and infant safety of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) procedures in young women aged ≤ 35 years. METHODS: A retrospective cohort study was performed to analyze the clinical data of 4,203 infertile women aged ≤ 35 years who underwent fresh embryo transfer (ET) in IVF/ICSI cycles. The data were collected from their initial visits to Fujian Maternity and Child Health Hospital between January 2015 and January 2022. Based on their ovarian reserve, the participants were categorized into two groups: DOR group (n = 1,027) and non-DOR group (n = 3,176). A propensity score matching (PSM) method was employed to ensure a relatively balanced distribution of covariates. The primary outcome assessed in this study was the live birth rate, while the secondary observation indicators included rates of high-quality embryo development, blastocyst formation, clinical pregnancy, and miscarriage, along with perinatal complications, neonatal birth weight, and the incidence of low birth weight (LBW). RESULTS: The DOR group showed notably lowered rates of blastocyst formation (59.8% vs. 64.1%), embryo implantation (29.8% vs.33.3%), clinical pregnancy (47.9% vs. 53.6%), and live birth (40.6% vs. 45.7%) compared to the non-DOR group (all P < 0.05). However, no statistically significant differences were observed in the high-quality embryo rate, miscarriage rate, perinatal complications, neonatal birth weight, or LBW incidence in infants between both groups (all P > 0.05). CONCLUSION: DOR has been found to reduce both clinical pregnancy and live birth rates in young females undergoing fresh ET in IVF/ICSI cycles. However, this reduction does not increase the risk of perinatal complications or LBW of infants through live birth cycles.

Estradiol Decline Before hCG Administration in COH Has a Negative Effect on IVF Outcomes in Patients Without OC Pretreatment.

Purpose: Together with ultrasound measurement of follicle size, serum estradiol (E2) provides guidance for controlled ovarian hyperstimulation (COH). However, during the COH process, some patients experience decreased serum E2 level, especially before human chorionic gonadotropin (hCG) trigger. In order to elucidate the effect of E2 reduction as well as the role of oral contraceptive pretreatment, a retrospective study was performed in our center from 2013 to 2019. Patients and Methods: In total, 333 patients who experienced an E2 decrease prior to hCG administration were recruited as E2 decline group, while 333 patients with continuously E2 increase during COH were considered as control group. Based on pretreatment strategy, the two groups were further categorized into oral contraceptive (OC) and non-OC sub-groups, and IVF and clinical outcomes were compared between paired groups. Results: Number of dominant follicles on hCG day and normally fertilized zygotes were significantly decreased in E2 decline group, and the significantly reduced live birth rate in E2 decline group indicated the close relationship between E2 decline and clinical outcomes. To analyse further, we found that in patients without OC pretreatment, the pregnancy rate and live birth rate of E2 decline group (n = 141) were significantly lower than control group (n = 136) (56.3% versus 68.0%, 50.8% versus 63.5%, respectively). However, for patients with OC pretreatment, no difference was detected between two groups, suggesting a potential effect of OC pretreatment on clinical outcomes. Conclusion: E2 decline prior to hCG-triggering day adversely affects IVF and clinical outcomes in patients without OC pretreatment, especially fertilization rate and live birth rate.

Progestogens in women with threatened miscarriage or recurrent miscarriage: A meta-analysis.

INTRODUCTION: Clinical practice guidelines provide inconsistent recommendations regarding progestogen supplementation for threatened and recurrent miscarriage. We conducted a systematic review and meta-analysis to assess the effectiveness and safety of progestogens for these patients. MATERIAL AND METHODS: We searched Medline, Embase, and Cochrane Central Registry of Controlled Trials up to October 6, 2023 for randomized control trials (RCTs) comparing progestogen supplementation to placebo or no treatment for pregnant women with threatened or recurrent miscarriage. We assessed the risk of bias using a modified version of the Cochrane risk-of-bias tool and the certainty of evidence using the GRADE approach. RESULTS: Of 15 RCTs (6616 pregnancies) reporting on threatened or recurrent miscarriage, 12 (5610 pregnancies) reported on threatened miscarriage with or without a prior history of miscarriage. Results indicated that progesterone probably increases live births (relative risk (RR) 1.04, 95% confidence interval (CI) 0.99-1.10, absolute increase 3.1%, moderate certainty). Of these RCTs, three (1973 pregnancies) reporting on threatened miscarriage with a prior history of miscarriage indicated that progesterone possibly increases live births (RR 1.06, 95% CI: 0.97-1.16, absolute increase 4.4%; low certainty), while four (2540 pregnancies) reporting on threatened miscarriage and no prior miscarriage left the effect very uncertain (RR 1.02, 95% CI: 0.96-1.10, absolute increase 1.7%; very low certainty). Three trials reporting on 1006 patients with a history of two or more prior miscarriages indicated progesterone probably increases live births (RR 1.08, 95% CI: 0.98-1.19, absolute increase 5.7%, moderate certainty). Six RCTs that reported on 2979 patients with at least one prior miscarriage indicated that progesterone probably increases live births (RR 1.07, 95% CI: 1.01-1.13, absolute increase 5.0%; moderate certainty). Progesterone probably has little or no effect on congenital anomalies (RR 1.06, 95% CI: 0.76-1.48, absolute increase 0.1%; moderate certainty), and other serious adverse pregnancy events (RR 1.07, 95% CI: 0.83-1.40, absolute increase 0.2%, moderate certainty). CONCLUSIONS: In women at increased risk of pregnancy loss, progestogens probably increase live births without increasing adverse maternal and neonatal events. It remains possible that the benefit is restricted to those with prior miscarriages.

Live birth outcomes following single-step blastocyst warming technique - optimizing efficiency without impacting live birth rates.

PURPOSE: To evaluate the impact of a single-step (SS) warming versus standard warming (SW) protocol on the survival/expansion of vitrified blastocysts and their clinical outcomes post-frozen embryo transfer (FET). METHODS: Retrospective analysis was performed on 200 vitrified/warmed research blastocysts equally divided amongst two thawing protocols utilizing the Fujifilm Warming NX kits (Fujifilm, CA). SW utilized the standard 14-minute manufacturer's guidelines. SS protocol required only a one-minute immersion in thaw solution (TS) before the embryos were transferred to culture media. A time-interrupted study was performed evaluating 752 FETs (SW: 376 FETs, SS 376 FETs) between April 2021-December 2022 at a single academic fertility clinic in Boston, Massachusetts. Embryologic, clinical pregnancy, and live birth outcomes were assessed using generalized estimated equation (GEE) models, which accounted for potential confounders. RESULTS: There was 100% survival for all blastocysts (n = 952 embryos) with no differences in blastocyst re-expansion regardless of PGT status. Adjusted analysis showed no differences in implantation, clinical pregnancy, spontaneous abortion, or biochemical pregnancy rate. A higher odds of multiple gestation [AdjOR(95%CI) 1.06 (1.01, 1.11), p = 0.019] were noted, even when adjusting for number of embryos transferred [AdjOR(95%CI) 1.05 (1.01, 1.10)]. Live birth outcomes showed no differences in live birth rates or birthweight at delivery. CONCLUSIONS: The study found equivalent outcomes for SS and SW in all parameters except for a slight rise in the rate of multiple gestations. The results suggest that SS warming is an efficient, viable alternative to SW, reducing thaw times without adverse effects on live birth rates or neonatal birth weights.

Does recurrent implantation failure exist? Prevalence and outcomes of five consecutive euploid blastocyst transfers in 123 987 patients.

STUDY QUESTION: What are the clinical pregnancy and live birth rates in women who underwent up to two more euploid blastocyst transfers after three failures in the absence of another known factor that affects implantation? SUMMARY ANSWER: The fourth and fifth euploid blastocyst transfers resulted in similar live birth rates of 40% and 53.3%, respectively, culminating in a cumulative live birth rate of 98.1% (95% CI = 96.5-99.6%) after five euploid blastocyst transfers. WHAT IS KNOWN ALREADY: The first three euploid blastocysts have similar implantation and live birth rates and provide a cumulative live birth rate of 92.6%. STUDY DESIGN, SIZE, DURATION: An international multi-center retrospective study was conducted at 25 individual clinics. The study period spanned between January 2012 and December 2022. A total of 123 987 patients with a total of 64 572 euploid blastocyst transfers were screened for inclusion. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients with a history of any embryo transfer at another clinic, history of any unscreened embryo transfer at participating clinics, parental karyotype abnormalities, the use of donor oocytes or a gestational carrier, untreated intracavitary uterine pathology (e.g. polyp, leiomyoma), congenital uterine anomalies, adenomyosis, communicating hydrosalpinx, endometrial thickness <6 mm prior to initiating of progesterone, use of testicular sperm due to non-obstructive azoospermia in the male partner, transfer of an embryo with a reported intermediate chromosome copy number (i.e. mosaic), preimplantation genetic testing cycles for monogenic disorders, or structural chromosome rearrangements were excluded. Ovarian stimulation protocols and embryology laboratory procedures including trophectoderm biopsy followed the usual practice of each center. The ploidy status of blastocysts was determined with comprehensive chromosome screening. Endometrial preparation protocols followed the usual practice of participating centers and included programmed cycles, natural or modified natural cycles. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 105 (0.085% of the total population) patients met the criteria and underwent at least one additional euploid blastocyst transfer after failing to achieve a positive pregnancy test with three consecutive euploid blastocyst transfers. Outcomes of the fourth and fifth euploid blastocyst transfers were similar across participating centers. Overall, the live birth rate was similar with the fourth and fifth euploid blastocysts (40% vs 53.3%, relative risk = 1.33, 95% CI = 0.93-1.9, P value = 0.14). Sensitivity analyses excluding blastocysts biopsied on Day 7 postfertilization, women with a BMI >30 kg/m2, cycles using non-ejaculate or donor sperm, double-embryo transfer cycles, and cycles in which the day of embryo transfer was modified due to endometrial receptivity assay test result yielded similar results. Where data were available, the fourth euploid blastocyst had similar live birth rate with the first one (relative risk = 0.84, 95% CI = 0.58-1.21, P = 0.29). The cumulative live birth rate after five euploid blastocyst transfers was 98.1% (95% CI = 96.5-99.6%). LIMITATIONS, REASONS FOR CAUTION: Retrospective design has its own inherent limitations. Patients continuing with a further euploid embryo transfer and patients dropping out from treatment after three failed euploid transfers can be systematically different, perhaps with regard to ovarian reserve or economic status. WIDER IMPLICATION OF THE FINDINGS: Implantation failure seems to be mainly due to embryonic factors. Given the stable and high live birth rates up to five euploid blastocysts, unexplained recurrent implantation failure should have a prevalence of <2%. Proceeding with another embryo transfer can be the best next step once a known etiology for implantation failure is ruled out. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

Predictors of success after in vitro fertilization.

The last few decades have witnessed a rise in the global uptake of in vitro fertilization (IVF) treatment. To ensure optimal use of this technology, it is important for patients and clinicians to have access to tools that can provide accurate estimates of treatment success and understand the contribution of key clinical and laboratory parameters that influence the chance of conception after IVF treatment. The focus of this review was to identify key predictors of IVF treatment success and assess their impact in terms of live birth rates. We have identified 11 predictors that consistently feature in currently available prediction models, including age, duration of infertility, ethnicity, body mass index, antral follicle count, previous pregnancy history, cause of infertility, sperm parameters, number of oocytes collected, morphology of transferred embryos, and day of embryo transfer.