Previous In Vitro Fertilization Research Articles

Does growth hormone supplementation of in vitro fertilization/intracytoplasmic sperm injection improve cumulative live birth rates in women with poor embryonic development in the previous cycle?

BackgroundGrowth hormone (GH) has been proposed as an adjunct in in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles, especially in women with poor ovarian response. However, it is unclear whether GH supplementation is effective in women with poor embryonic development in the previous IVF cycle. The aim of this study was to evaluate the effectiveness of GH supplementation in IVF/ICSI cycles in women with poor embryonic development in the previous cycle.MethodsThis is a retrospective cohort study from a public fertility center in China, in which we performed propensity score-matching (PSM) for female age and AFC in a ratio of 1:1. We compared the cumulative live birth rate per started cycle, as well as a series of secondary outcomes. We included 3,043 women with poor embryonic development in the previous IVF/ICSI cycle, of which 1,326 had GH as adjuvant therapy and 1,717 had not. After PSM, there were 694 women in each group.ResultsAfter PSM, multivariate analyses showed the cumulative live birth rate to be significantly higher in the GH group than the control group [N = 694, 34.7% vs. N = 694, 27.5%, risk ratio (RR): 1.4 (95%CI: 1.1–1.8)]. Endometrial thickness, number of oocytes retrieved, number of embryos available, and number of good-quality embryos were significantly higher in the GH group compared to controls. Pregnancy outcomes in terms of birth weight, gestational age, fetal sex, preterm birth rate, and type of delivery were comparable. When we evaluated the impact of GH on different categories of female age, the observed benefit in the GH group did not appear to be significant. When we assessed the effect of GH in different AFC categories, the effect of GH was strongest in women with an AFC5-6 (32.2% versus 19.5%; RR 2.0; 95% CI 1.2–3.3).ConclusionsWomen with poor embryonic quality in the previous IVF/ICSI cycles have higher rates of cumulative live birth with GH supplementation.

Unlocking Infertility: Enhancing Pregnancy Rates With Personalized Embryo Transfers Using Optimal Time for Endometrial Receptivity Analysis in Recurrent Implantation Failure Patients Undergoing In Vitro Fertilization.

Background Infertility remains a significant global challenge, and recurrent implantation failure (RIF) poses a considerable concern in assisted reproductive technology. Understanding the factors contributing to implantation failure is essential for developing accurate diagnostic tools and treatment strategies. Endometrial receptivity (ER) during the window of implantation is crucial for successful embryo implantation in in vitro fertilization (IVF) procedures. Molecular-based endometrial receptivity analysis and next-generation sequencing provide insights into ER, but there is a lack of research on these in the Indian population, particularly in patients with RIF. This retrospective cohort study evaluates the effectiveness of Optimal Timing for Endometrial Receptivity Analysis (OpERA)-guided personalized embryo transfer (pET) in Indian patients with a history of RIF. Methodology The study includes 158 female patients with a history of failed embryo transfers who underwent OpERA testing before frozen embryo transfer. Patients were categorized based on the number of previous failed transfers. OpERA outcomes were assessed, and clinical outcomes were compared between groups undergoing preimplantation genetic testing for aneuploidy (PGT-A) with and without OpERA. Endometrial preparation involved hormone replacement therapy, and OpERA testing was performed at the Neuberg Centre for Genomic Medicine using RNA extraction, cDNA conversion, and sequencing. Results OpERA outcomes showed no significant differences in receptive rates among patient groups. Group 3, with three or more failed transfers, exhibited significantly higher biochemical pregnancy rates (BPRs), clinical pregnancy rates (CPRs), and abortion rates (ARs) compared to Groups 1 and 2. OpERA with PGT-A showed significantly higher BPR, implantation rate, CPR, and lower AR compared to OpERA without PGT-A. Conclusions OpERA-guided pET, especially with PGT-A, demonstrated improved pregnancy outcomes, particularly in patients with a history of RIF. The study emphasizes the importance of OpERA in determining optimal transfer timing, moving beyond the traditional reliance on embryo quality alone.OpERA presents promise in predicting pregnancy outcomes for Indian patients with previous IVF failures. The integration of OpERA and PGT-A represents a significant advancement in personalized reproductive medicine, offering new hope for individuals grappling with infertility complexities.

#21 : Letrozole Can Be a Good Adjuvant for In Vitro Fertilization (IVF) Procedure in Patient with Ovarian Endometriosis

Background and Aims: To evaluation the pregnancy rate in IVF procedure with letrozole in patient with ovarian endometrioma. Method: Prospective study performed by single physician at primary fertility center. From August 2016 to November 2019, 109 cycles of IVF were performed from couples who were diagnosed as endometrioma. 40 women were diagnosed during ovarian cystectomy, 69 were by transvaginal ultrasonography. In 64 cycles, gonadotrophic releasing hormone (GnRH) antagonist protocol was used, and in another 45 cycles, gonadotrophin releasing hormone agonist (GnRHa) protocol were applied. In every cycle, 10 mg of letrozole was added from the start of gonadotrophin till the end of ovarian stimulation. Results: Women’s age was 36.10±3.67, and the number of their previous IVF cycle was 2.66±1.63. AMH was 2.30±2.31, follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) on the third day of menstruation were 9.40±5.26, 7.81±4.60 and 54.1±44.2. Start dosages and total dosages of recombinant FSH were 314.32±74.99 and 2541.37±992.77, and serum E2 and progesterone on trigger day were 1220.06±1072.49 and 0.92±0.79. The endometrial thickness was 9.20±1.46. The number of obtained oocytes was 9.05±5.94 and metaphase II(M2) oocytes were 6.71±4.12. 1.91±0.42 embryos were transferred to the uterine cavity and 2.68±2.58 surplus embryos were cryopreserved. Pregnancy rate was diagnosed if serum beta human chorionic gonadotrophin (hCG) level was above 5 ng/ml on 14th day after oocyte retrieval, and the result was 44.95% (49/109). Clinical pregnancy rate which was defined if gestational sac was visualized by transvaginal ultrasonography after at least 21st days after oocyte retrieval, and the result was 24.77% (27/109). Conclusion: In IVF procedure for the patients with ovarian endometrioma, just adding letrozole to conventional controlled ovarian hyperstimulation protocol can reduce serum peak E2 level without make harmful effect on uterine endometrium, and result in comparable pregnancy rate.

Comparison of dydrogesterone plus progesterone gel with subcutaneous aqueous progesterone plus progesterone gel for luteal phase supplementation of subsequent in vitro cycle in women after previous cycle failure.

The luteal phase supplementation (LPS) of the in vitro fertilization (IVF) cycle is crucial to increase the chance of a live birth. There is no preferred progestogen for use in the general population. The optimal progestogen regimen in the event of prior IVF failure is unknown. The aim was to compare the live birth rate for dydrogesterone plus progesterone gel versus aqueous progesterone plus progesterone gel in LPS of the IVF cycle in women with at least one previous IVF failure. A prospective randomized single-center study enrolled women with at least one previous IVF failure undergoing another IVF cycle. Women were randomly assigned in a 1:1 ratio to 2 arms depending on LPS protocol: dydrogesterone (Duphaston®) + progesterone in vaginal gel (Crinone®) vs aqueous progesterone solution in subcutaneous injection (Prolutex®) + progesterone in vaginal gel (Crinone®). All women underwent fresh embryo transfer. The live birth rate with one prior IVF failure was 26.9% for D + PG vs 21.2% for AP + PG (p = 0.54), and with at least two IVF failures: 16% for D + PG vs 31.1% for AP + PG (p = 0.16). There were no significant differences in live birth rates between protocols, regardless of the number of prior IVF failures. In light of the evidence from this study that neither of the two LPS protocols is more effective in women with prior IVF failure, other factors, such as potential side effects, dosing convenience and patient preference, should be considered when choosing a treatment.

Should ICSI be implemented on patients with poor-quality embryos in the previous IVF cycle?

This study was to evaluate whether Intracytoplasmic sperm injection (ICSI) can improve the quality of embryo in patients with poor-quality embryos in the previous In-vitro fertilization (IVF) cycle, which was cancelled before transfer. This was a retrospective cohort study of 178 IVF and 158 ICSI cycles for patients with poor-quality embryos in the previous IVF cycle in the Center for Reproductive Medicine, Women and Children's Hospital of Chongqing Medical University from March 2016 to June 2022. The 2 PN rate, oocyte utilization rate , high-quality embryo rate and clinical pregnancy rate were compared between the two groups. Furthermore, the implantation rate, miscarriage rate and cycle cancelation rate were measured and compared. ICSI resulted in a comparable 2 PN rate, oocyte utilization rate and cycle cancelation rate with IVF. The high-quality embryo rate of ICSI group was significantly higher than that of IVF group (5.56% vs. 2.60%, P < 0.05). Eventually, a total of 239 patients performed embryo transfer. ICSI resulted in a significantly higher clinical pregnancy rate (55.56% vs. 40.98%, P < 0.05) compared with IVF, however, there were no notable differences in miscarriage rate and implantation rate. The present study suggested that ICSI significantly improved the high-quality embryo rate and clinical pregnancy of the patients with poor-quality embryos in the previous IVF cycle. Prospective randomized controlled trials are needed to further verify.

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

Letrozole cotreatment improves the follicular output rate in high-body-mass-index women with polycystic ovary syndrome undergoing IVF treatment.

Women who have polycystic ovary syndrome (PCOS) with high body mass index (BMI) typically have an attenuated ovarian response and decreased follicular size, which are linked to unfavourable clinical outcomes following in vitro fertilization (IVF) therapy. The follicular output rate (FORT), a qualitative indicator of follicular response, seems to be positively linked to the clinical outcomes of IVF. Progestin-primed ovarian stimulation (PPOS) has become an alternative to gonadotropin-releasing hormone (GnRH) analogues to inhibit the premature luteinizing hormone (LH) surge. As letrozole (LE) shows promise in enhancing ovarian response, we compared PPOS with and without LE for PCOS in high BMI women with a focus on the FORT and associated clinical and pregnancy outcomes. For the recruited 1508 women, ten variables including AFC; age; basal sex hormone level; BMI; infertility type; period of infertility and number of previous IVF attempts were chosen in the propensity score matching (PSM) model to match 1374 women who taken the MPA+ hMG protocol with 134 women who received the MPA+ hMG+ LE treatment at a 1:1 ratio. FORT was selected as the primary outcome measure. The number of oocytes retrieved, viable embryos, hMG dosage, duration, oocyte maturity rate, fertilization rate, and implantation rate were established as secondary outcomes. FORT was substantially elevated in the MPA+hMG+LE group compared with the MPA+hMG group (61% [35%, 86%] vs. 40% [25%, 60%], P <.001). Interestingly, the LE cotreatment group had a considerably lower mature oocyte rate despite having a similar number of mature oocytes and embryos recovered. The average hMG dosages and durations in the study group were similar to those in the control group. The implantation rate in the study group was numerically higher but without statistic significant than that in the control groups (43.15% (107/248) vs. 38.59% (115/298), OR 1.008, 95% CI 0.901-1.127; P >.05). The effect of LE combined with PPOS on FORT is better than the effect of the standard PPOS treatment in women with PCOS and a high BMI, but there is no substantially beneficial impact on pregnancy outcomes or the cycle features of COS, including consumption of hMG.

First pilot study of maternal spindle transfer for the treatment of repeated in vitro fertilization failures in couples with idiopathic infertility

To gain insights into the technical feasibility of maternal spindle transfer (MST) applied in the context of repeated invitro fertilization (IVF) failures for the treatment of idiopathic infertility. A prospective pilot study. IVF center. Twenty-five infertile couples with multiple previous unsuccessful IVF cycles (range, 3-11), no previous pregnancy, and no history of mitochondrial DNA (mtDNA) disease participated. The study focused on women <40 years, with previous IVF attempts characterized by a pattern of low fertilization rates and/or impaired embryo development. Couples with severe male-factor infertility were not eligible. Oocyte donors with previous successful IVF outcomes were matched with patients according to standard practice. We performed MST by transferring metaphase II spindles from the patients' oocytes into the previously enucleated donor oocytes, followed by intracytoplasmic sperm injection, invitro embryo culture, blastocyst biopsy, and vitrification. Only euploid blastocysts were considered for embryo transfer. Outcome measures included oocyte fertilization, blastocyst development, clinical pregnancy and live birth, incidence of mitochondrial carryover and potential mtDNA reversal, as well as general health of the children born. Twenty-eight MST cycles produced 6 children (19 embryo transfers, 7 clinical pregnancies). Pediatric follow-up of the children, performed at intervals from birth to 12-24 months of age, revealed their development to be unremarkable. DNA fingerprinting confirmed that the nuclear DNA of MST children was inherited from both parents, without any contribution from the oocyte donor. For 5 of the children, mtDNA was derived almost exclusively (>99%) from the donor. However, 1 child, who had similarly low mtDNA carryover (0.8%) at the blastocyst stage, showed an increase in the maternal mtDNA haplotype, accounting for 30% to 60% of the total at birth. This pilot study provides the first insights into the feasibility of applying MST for patients with idiopathic infertility and repeated IVF failures. Reconstructed oocytes produced embryos capable of implanting, developing to term and producing apparently healthy newborns/children. However, claims concerning the efficacy of MST with respect to infertility treatment would be premature considering the limitations of this study. Importantly, mtDNA reversal was detected in one child born after MST, a finding with possible implications for mitochondrial replacement therapies. Pilot trial registry number, ISRCTN11455145. The date of registration: 20/02/2018. The date of enrolment of the first patients: 18/03/2018.

Pathways to social support: IVF patients’ motivation toward peers and selection preferences

Infertility rates are increasing internationally, and its treatment, in-vitro fertilization (IVF) imposes stress on women as primary patients. In this study, led by a researcher with lived experience in infertility, we seek to uncover the pathways that lead IVF patients toward peer support; mainly what precipitates patients’ decisions to seek peer support and how they select their peer. Having interviewed 23 IVF patients, we found that prior to disclosing to a peer, women reflect on information about their condition and their personal support needs and reconcile support gaps within their couple and social circles as they gauge their personal motivation to seek peer support. The demands of IVF compel patients to gravitate toward other women with shared experience. Prior to disclosure, patients consider diverse points of connection as well as desirable peer traits including previous IVF experience, other common ground and full transparency in a peer’s communication style.

Preimplantation genetic testing for aneuploidy: helpful but not a first choice.

This retrospective cohort study aimed to assess and compare the outcomes between cumulative live birth of patients with and without PGT-A and also between prior unsuccessful IVF cycles and PGT-A cycles among patients who experienced IVF but without live birth delivery, and to clarify the effective usage of PGT-A as an in vitro fertilization (IVF) add-on. A total of 2113 females undergoing IVF with at least one blastocyst were reviewed. Patients in the PGT-A and non-PGT-A groups were further categorized into first-time IVF and prior unsuccessful IVF groups (previous IVF experience but without live birth delivery). In the PGT-A group, there were additional oocyte retrieval cycles, fewer transfer cycles per patient, higher clinical pregnancy rates per embryo transfer, and lower miscarriage rates per clinical pregnancy as compared to the non-PGT-A group, all showing significant differences. However, the first-time IVF group with PGT-A had a significantly longer duration from the first oocyte retrieval to the first live birth delivery (LBD) and a significantly lower LBD rate per patient than the non-PGT-A group. The cumulative probability for a first LBD with PGT-A was inferior in the first-time IVF group for women < 35years, marginally superior in the prior unsuccessful IVF group of women aged 38-40years, and similar for other groups. PGT-A should not be recommended to all patients; however, if the first IVF treatment failed, PGT-A may reduce the patient's burden regardless of age.

P-604 Improving IVF treatment outcomes via intraovarian injection of autologous platelet rich plasma: a prospective clinical trial

Abstract Study question Does the intraovarian injection of autologous platelet rich plasma (A-PRP) improve the outcomes of subsequent in vitro fertilisation (IVF) treatments. Summary answer Intraovarian injection of A-PRP improves embryological performance and pregnancy outcomes in subsequent IVF treatments, but the beneficial effects may be lost with time. What is known already A-PRP has been widely used in other medical fields to optimise treatment outcomes. In IVF, emerging evidence has shown its potential benefit in promoting endometrial quality via release of a range of growth factors and cytokines. More recently it has been proposed that intraovarian injection of A-PRP may have the potential to “activate” some resting follicles in a selected group of patients. In this registered clinical trial, we aimed to evaluate embryology performance and pregnancy outcomes following ovarian injection of A-PRP in patients with poor ovarian function or premature ovarian failure. Study design, size, duration This is a registered (ID= ACTRN126190012061128) prospective clinical trial with recruitment commencing in November 2019. All participating women undergoing A-PRP treatment due to poor ovarian function or premature ovarian failure were reviewed for eligibility for this study. Inclusion criteria were restricted to women who had completed at least one IVF cycle before and after A-PRP injection as of January 2022. Participants/materials, setting, methods All A-PRP treatments were prepared using a commercial kit (Alocuro) approved by the Australian Therapeutic Goods Agency. Up to 3 subsequent IVF cycles post A-PRP injection were included for analysis. Embryological parameters included numbers of follicles, oocytes and embryos yielded per cycle. Paired comparisons were performed between cycles of the same patients before and after A-PRP injection. Cumulative ongoing pregnancy outcomes were also evaluated up to 3 IVF cycles post A-PRP injection. Main results and the role of chance 36 women were included in the analysis, average age 41.14±3.56 years with 4.61±2.91 unsuccessful previous IVF attempts at the time of A-PRP injection. Their serum FSH was reduced from 13.04±8.97 mIU/mL before A-PRP injection to 11.06±.56 mIU/mL post injection. In reference to the IVF cycle immediately before A-PRP injection, an improving trend in the embryology parameters was identified in the subsequent 1st, 2nd, and 3rd IVF cycles; as demonstrated in the numbers of follicles (2.39±1.76, 2.86±2.06, 2.52±1.65 and 2.46±1.66), oocytes (1.86±1.48, 2.56±2.08, 2.43±1.90 and 2.08±1.93) and embryos (1.30±1.03, 1.45±1.39, 1.80±1.67 and 1.20±1.48). Although the comparisons above did not reach statistical significance, the rise in oocyte numbers in the 1st IVF cycle was close to statistical significance (P = 0.08). It should also be noted that the highest improvement in follicle and oocyte numbers was seen in the 1st IVF cycle after A-PRP injection, while embryo number peaked at the 2nd IVF cycle. Three out of 36 women (P = 0.08) achieved ongoing pregnancies after the 1st round IVF cycles with inclusion of associated frozen embryo transfers as applicable. After the 2nd round, 4 out of the 36 women (P = 0.04) achieved ongoing pregnancy but no additional pregnancies from the 3rd round. Limitations, reasons for caution Comparisons performed in this study were not randomised, with the patients themselves used as their own controls. Therefore cycle associated variations may not be eliminated. Sample size was relatively small, and findings were restricted to a selected patient group. Wider implications of the findings Ovarian injection of A-PRP seems to improve both embryology performance and cumulative pregnancy outcomes. However the beneficial effect post injection seems to fade with time. A further randomised study is warranted to specify the timeframe of this diminishing effect in order to better guide clinical practice. Trial registration number ACTRN126190012061128

P-429 The prevalence and assessment of uterine natural killer cells (uNK) by Immunohistochemistry (IHC) in women undergoing IVF

Abstract Study question What is the prevalence of raised uNK cells in an IVF population? Identifying demographic factors that are predictive of a raised uNK result? Summary answer The prevalence of uNK was high for those with RIF and history of miscarriage. Age was the only statistically significant factor for predicting positive results. What is known already uNK cells play two important roles in implantation; regulation of trophoblastic invasion and spiral artery modelling. Both these crucial mechanisms are required for bringing about a state of endometrial receptivity. The current evidence is centred on raised uNK status in women undergoing IVF being associated with a detrimental pregnancy outcome. This could be either due to NK cells being cytotoxic to embryo endometrium complex or causing aberrant placentation. Their exact function is unclear and the prevalence has only been determined in small observational studies. Study design, size, duration This was a prospective analysis of 203 patients who had uNK testing through immunohistochemistry and subsequently embarked on IVF treatment. Patients undergoing both fresh and frozen in vitro fertilisation (IVF) cycles at NURTURE fertility, Nottingham, UK were approached over a period of 6 months at different stages of their fertility history. Participants/materials, setting, methods uNK biopsy was arranged one month before undergoing IVF to ensure results before embryo transfer. The procedure was carried out in the mid-luteal phase of the menstrual cycle (day 19-24). Samples were fixed and analyzed by IHC. The age, BMI, timing of the biopsy, cause of infertility was recorded. The details of the subsequent IVF cycle, embryo quality, and pregnancy outcome were also collected prospectively. The data was analyzed using SPSS version 25. Main results and the role of chance The prevalence of raised uNK status was noted to be 61.6% (CI 54.9-68.3) in the IVF population. Furthermore the prevalence in women with no previous IVF treatment (primary infertility) was also high 66.7% (CI 54.4-78.9). One of the main strengths of this work was women were recruited from a highly successful IVF center. The clinical pregnancy rates are 2-3 fold higher than the national average e.g. 65% for women aged under 35 versus 29% respectively (HFEA 2018). This is mainly due to stringent laboratory processes leading to the creation of optimal quality embryos and their transfer. Therefore if IVF did not result in a pregnancy, then endometrial receptivity or adverse maternal immunology could be contributory factors. Although the prevalence of raised uNK status was high for those with RIF and a history of miscarriage, there were only statistically significant associations found for age in terms of predicting a positive result. Therefore IHC has to be complimented with another technique such as flow cytometry to determine if uNK is significant in implantation and pregnancy success. Limitations, reasons for caution uNK status is influenced by hormonal, menstrual cycle variability, pathogenic and laboratory interpretation. Therefore to gauge an accurate assessment of whether immune cells are implicated in pregnancy, a functional aspect of study or repeat sampling in the same cycle is required. Wider implications of the findings It is known that immune cell function declines with age. They may also be detrimental to pregnancy outcomes and contribute to the age-related decline in fertility. Designing a randomized controlled trial whereby patients tested for uNK are allocated to therapy such as prednisolone. This may address both issues. Trial registration number N/A

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

An audit of clinical outcomes following ovarian administration of platelet-rich plasma (PRP) in women with severe diminished ovarian reserve.

Infertility caused by poor oocyte quality is one of the most difficult areas to manage. While oocyte donation is an effective treatment, for most women it is a treatment of last resort. Ovarian platelet-rich plasma (PRP) treatment is a relatively new adjunct therapy which has been reported to possibly improve oocyte quality and in vitro fertilisation (IVF) treatment outcomes in women with severe diminished ovarian reserve. To audit IVF and pregnancy outcomes following ovarian PRP treatment in a cohort of women under 45 years of age with severe diminished ovarian reserve and previous IVF treatment failure. An audit of 20 consecutive patients comparing embryology outcomes before and after ovarian PRP treatment, together with assessment of PRP-related pregnancies and treatment complications. Overall, PRP treatment produced no significant improvement in oocyte number, but did increase the number of embryos generated compared to patients' own pre-PRP IVF cycle (zero vs two embryos, P= 0.005). In total four patients conceived viable genetically normal pregnancies in their next IVF cycle, and a further two conceived naturally within 4months of the PRP treatment. Five of these pregnancies were in women 40 years or older, all being euploid on non-invasive pregnancy screening and viable beyond 12 weeks gestation. No operative complications were observed. Ovarian PRP treatment appears to be low risk and may offer some promise in assisting pregnancy (natural and IVF-related), especially in women with reduced oocyte quality due to advanced maternal age. Future randomised controlled trials are urgently required to confirm this benefit.

Predicting the probability of a live birth after a freeze-all based in vitro fertilization-embryo transfer (IVF-ET) treatment strategy.

BackgroundThe predictors for live birth rate (LBR) following one episode of in vitro fertilization (IVF) cycle for patients using a “freeze-all” strategy are not entirely clear.MethodsA retrospective cohort study utilizing a prediction model was developed to assess the relationship to the LBR. Women undergoing IVF with a freeze-all strategy were screened. Univariate models were first fitted for female age at oocytes retrieval/frozen-thawed embryo transfer (FET), body mass index (BMI), duration and etiology of infertility, previous IVF failures, total dose and duration of gonadotrophin, ovarian sensitivity index (OSI), number of oocytes collected, method of fertilization, number of embryos created, number and stage of embryos frozen, type and number of FET cycles, endometrial thickness (EMT)/pattern, hormone level on transplantation day, storage duration, number of embryos thawed and damaged thawed embryos, number and stage of embryos transferred and number of different quality embryos transferred. Variables with P<0.05 in the univariate model were selected for further analysis of the final multivariate discrete-time logistic regression model.ResultsA total of 7,602 women undergoing one ovarian stimulation resulted in 9,964 FETs, of whom 3,066 (40.33%) had a live-birth after their first FET and 3,929 (51.68%) after total FETs. The EMT and woman’s age at oocyte retrieval were the most important predictors. In the first FET, the LBR of women with an EMT ≤8 mm [27.40%; 95% confidence interval (CI): (21.60–33.81%)] was significantly lower than that of women with EMT between 9 and 11 mm [36.51%; 95% CI: (34.25–38.81%)] and thicker than 12 mm [44.23%; 95% CI: (42.22–46.25%)] (P<0.05). The optimistic and conservative cumulative LBRs of women younger than 31 years [87.5%; 95% CI: (86.32–88.61%) and 63.04%; 95% CI: (61.36–64.69%)] were significantly decreased in women aged 31–35, 36–40 and >40 (P<0.001).ConclusionsOur study provides an effective prediction model for a woman’s chance of having a baby after a “freeze-all” policy. The use of EMT and female age as tools to identify LBR are shown to be justified, and repeated FETs cannot reverse the age-dependent decline in fertility.

Factors associated with frequency of ectopic pregnancy

Background/Aim: Ectopic pregnancy is defined as a pregnancy outside the uterine cavity, most often in the fallopian tube. It is a life-threatening condition and requires early diagnosis and adequate care. Aim of this study was to examine the frequency of ectopic pregnancy, as well as the influence of parity, age of patients and previous in vitro fertilisation (IVF) procedure on the occurrence of ectopic pregnancy. Methods: A retrospective research was conducted in the Clinic for Gynaecology and Obstetrics of the University Clinical Centre of the Republic of Srpska from 1st of January 2016 up to 31 of December 2018, which included 125 hospitalised patients with a confirmed diagnosis of ectopic pregnancy. Data on the age of patients , parity and previous IVF, as well as the method of treatment of patients with ectopic pregnancy were analysed and compared. Results: In the observed period, there were a total of 9781 births and in the same period, 125 patients with a diagnosis of ectopic pregnancy were hospital-ised, which is 1.27 %. Pregnancy did not occur after IVF. Laparoscopy and drug therapy are represented almost equally, depending on the clinical picture and the wishes of the patients and open access was represented only sporadically. Conclusion: According to this research, the onset of ectopic pregnancy is not affected by age, parity and previous IVF, which does not fit into the results of world research. The most common form of treatment in our country is both lap-aroscopy and medical approach and open access occurs only sporadically, which fits into the recommendations of the relevant guides.

Impact of growth hormone supplementation on improving oocyte competence in unexplained poor embryonic development patients of various ages

Objectives To evaluate the effectiveness of Growth hormone (GH) co-treatment during in vitro fertilization (IVF) cycles in women of different ages who manifest unexplained poor embryonic development. Method This cohort study included a total of 2647 patients with unexplained poor embryonic development in their previous IVF procedures: 872 women received GH co-treatment and 1775 untreated women served as a control group. Patients were divided into 6 groups according to treatment and stratified by age (<35 years of age, A-GH group and A-control group; 35–40 years, B-GH group and B-control group; and ≥40 years, C-GH group and C-control group). The primary outcome was the oocyte-cleavage rate and the clinical pregnancy rate (CPR). Results The oocyte-cleavage rates among the three age groups were significantly higher in the GH group compared to the same-aged control group. In both group A and group B, there was no significant difference in clinical pregnancy rate between the GH group and controls. However, in patients ≥40 years of age, the clinical pregnancy rate in the GH group was significantly higher than in the control group (31.8% vs. 13.7%, p = 0.019). In the three age groups, there was no significant difference in the live birth rate between the GH group and controls. In the multivariate logistic regression analysis model, in both group A and group B, the number of cleaved embryos was independent predictors for CPR (OR = 1.464, 95% CI: 1.311–1.634; respectively, OR = 1.336, 95% CI: 1.126–1.586); Besides, in both group B and group C, age was independent predictors for CPR (OR = 0.657, 95%CI: 0.555–0.778; respectively, OR = 0.622, 95%CI: 0.391–0.989). However, only in group C, supplementation GH increased CPR as compared with not supplementation GH (OR = 2.339, 95%CI: 1.182–6.670). Conclusions For patients with unexplained poor embryonic development, supplementation with GH increased the oocyte-cleavage rates in all three age groups, and the clinical pregnancy rate gradually improved commensurate with increasing age. There was no difference in the clinical pregnancy rate in group A and group B, but group C improved significantly. Therefore, compared with patients under 40 years of age, patients ≥40 may benefit more from GH supplementation.

Predicting personalized cumulative live birth following in vitro fertilization

To develop invitro fertilization (IVF) prediction models to estimate the individualized chance of cumulative live birth at two time points: pretreatment (i.e., before starting the first complete cycle of IVF) and posttreatment (i.e., before starting the second complete cycle of IVF in those couples whose first complete cycle was unsuccessful). Population-based cohort study. National data from the Society for Assisted Reproductive Technology (SART) Clinic Outcome Reporting System. Based on 88,614 women who commenced IVF treatment using their own eggs and partner's sperm in SART member clinics. Not applicable. The pretreatment model estimated the cumulative chance of a live birth over a maximum of three complete cycles of IVF, whereas the posttreatment model did so over the second and third complete cycles. One complete cycle included all fresh and frozen embryo transfers resulting from one episode of ovarian stimulation. We considered the first live birth episode, including singletons and multiple births. Pretreatment predictors included woman's age (35 years vs. 25 years, adjusted odds ratio 0.69, 95% confidence interval 0.66-0.73) and body mass index (35 kg/m2 vs. 25 kg/m2, adjusted odds ratio 0.75, 95% confidence interval 0.72-0.78). The posttreatment model additionally included the number of eggs from the first complete cycle (15 vs. 9 eggs, adjusted odds ratio 1.10, 95% confidence interval 1.03-1.18). According to the pretreatment model, a nulliparous woman aged 34 years with a body mass index of 23.3 kg/m2, male partner infertility, and an antimüllerian hormone level of 3 ng/mL has a 61.7% chance of having a live birth over her first complete cycle of IVF (and a cumulative chance over three complete cycles of 88.8%). If a live birth is not achieved, according to the posttreatment model, her chance of having a live birth over the second complete cycle 1 year later (age 35 years, number of eggs 7) is 42.9%. The C-statistic for all models was between 0.71 and 0.73. The focus of previous IVF prediction models based on US data has been cumulative live birth excluding cycles involving frozen embryos. These novel prediction models provide clinically relevant estimates that could help clinicians and couples plan IVF treatment at different points in time.

P–674 Development of a predictive model indicating the population of poor responders benefiting from luteal phase oocyte retrieval

Abstract Study question Can successful implementation of luteal phase oocyte retrieval (LuPOR) following conventional follicular phase oocyte retrieval (FoPOR) be predicted for poor ovarian response (POR) patients? Summary answer Antral follicle count (AFC), number of small follicles recorded in FoPOR, and estradiol (E2) levels on FoPOR and LuPOR trigger days, predict successful LuPOR application. What is known already A second follicular wave in the same menstrual cycle was first observed in domestic animals such as horses and cattle and thenceforth in women. The second follicular wave has been introduced as an encouraging means towards optimizing the context of in vitro fertilization (IVF) success rates for infertile women and especially for POR patients. Double ovarian stimulation coupled with two oocyte retrievals in the same menstrual cycle has been proposed, and encouraging results have been reported. However, the high heterogeneity characterizing POR patients dictates that studies should focus on factors indicating efficient LuPOR application. Study design, size, duration This retrospective observational study included 1688 women diagnosed with POR, undergoing natural IVF cycles between 2012–2020 including two oocyte retrievals in the same menstrual cycle. Patients’ age, body mass index (BMI), number of previous POR incidences, basal hormonal levels, AFC, E2 evaluated on both trigger days and number of small follicles (8–13 mm) were evaluated on their predictive power regarding retrieval of at least one MII oocyte following LuPOR, being regarded as successful LuPOR implementation. Participants/materials, setting, methods A diagnosis of POR according to Bologna criteria served as the inclusion criterion for this single center study. All other infertility etiologies were excluded. Patient dataset was stratified according to age in quantiles. A random 20% of each quantile was employed to validate the model. The remaining 80% was employed to develop this model. The predictive value was determined employing the Area Under the Curve (AUC) of the Receiver Operating Characteristics, employing Youden’s index. Main results and the role of chance Patients’ age, BMI, number of previous failed IVF attempts, basal levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin and progesterone failed to be predictive of a successful LuPOR as the AUC was below 0.6. AFC with a threshold value of 4.47, was found to be predictive of an effective LuPOR with an AUC of 0.86, sensitivity 0.8, specificity 0.75, and accuracy 0.79. E2 levels evaluated on the FoPOR trigger day, with a threshold value of 232.66 pg/ml, were similarly predictive of an effective LuPOR presenting with an AUC 0.86, specificity 0.75, sensitivity 0.86 and accuracy 0.82. Similarly, E2 evaluated on the LuPOR trigger day, with a threshold value of 200.89 pg/ml, presented with an AUC 0.89, specificity 0.85, sensitivity 0.95 and accuracy 0.92. The number of small follicles during FoPOR also appeared to be predictive of the presence of at least one MII oocyte during LuPOR, with a threshold value of 2.94. The AUC was 0.82, specificity 0.75, sensitivity 0.76 and accuracy 0.75. When combining the above characteristics into a single predictive model the AUC was 0.88, specificity 0.73, sensitivity 0.94 and accuracy 0.89. The positive and negative predictive value of the model were 93.5% and 46.8%, respectively. Limitations, reasons for caution Employment of natural cycles may present as a limitation when examining the value of this study, as the cut-off values reported herein may be altered when stimulation is employed. Since internal validation may be confounded by the fact that this was a single center study, external validation is required. Wider implications of the findings: The clinical end-point of this study reporting back to the practitioner, is the development of a predictive model identifying the optimal POR population for whom LuPOR practice is valuable. The high positive predictive value of this model may assist clinicians in identifying poor responders who will benefit from this approach. Trial registration number Not applicable

P–415 Clinical and In Vitro Fertilization laboratory parameters that contribute to clinical miscarriage after single euploid embryo transfer

Abstract Study question To investigate which factors, excluding embryo aneuploidies, are associated with miscarriage in patients who have undergone a single euploid blastocyst transfer. Summary answer Miscarriage was related to the body mass index (BMI), the type of cycle and the thickness of the endometrium. What is known already Preimplantation genetic testing for aneuploidies (PGT-A) is widely used in-vitro fertilization (IVF) to select euploid embryos. Several studies have shown that embryo aneuploidy is the main contributing factor for IVF failure, reinforcing the relevance of PGT-A as a method to select chromosomally normal embryos. A recent meta-analysis confirmed that patients undergoing PGT-A have a lower miscarriage rate than women that conceived naturally (9% vs 28%, respectively). Even though most of the studies show that PGT-A significantly reduces miscarriage rate, still some women do lose their pregnancies. We investigated which other reasons may be related to this early pregnancy loss. Study design, size, duration Retrospective, observational, and multicenter study of 6910 patients undergoing single euploid blastocyst transfer after PGT-A from January 2017 to December 2019 in our institution. Several laboratory and clinic variables were analyzed to study the effect of these variables on the miscarriage rate Participants/materials, setting, methods Indications for PGT-A were advanced maternal age, implantation failure, recurrent pregnancy loss and male factor. Embryos were cultured 5% O2 concentration and 6.5% CO2 concentration. Trophectoderm biopsy was performed on day 5/6 of development and analyzed through Next Generation Sequencing (NGS); embryos were vitrified until transfer was performed. Single euploid embryo transfer was performed in all cases. We performed a multivariate regression analysis to compare the different variables and search for there are significant differences. Main results and the role of chance We studied a total of 6910 patients undergoing PGT-A to describe which factors, excluding embryo aneuploidies, were correlated with miscarriage in patients who underwent single thawed euploid embryo transfer. When considering embryo morphology (embryo grading, quality of inner cell and quality of trophectoderm), we did not find differences in miscarriage rate among groups (high quality= 15.9%; normal quality= 14.3%; low quality= 15.0%; poor quality= 14.8%) p = 0.833. BMI was significantly associated with miscarriage rate (odds ratio [OD] 1.04; 95% confidence interval [CI], 1.012–1–076 p = 0.006) and miscarriage rate. We observed a weak association between endometrial thickness and miscarriage rate ([OD] 0.65; 95%, 0.528–0.778 p = 0.04) and also between type of endometrial preparation (natural cycle or hormone replacement cycle) ([OD] 0.77; 95%, 0.528–0.778) p = 0.04. Body mass index, according to our findings, was the main variable correlated with miscarriage rate. We did not find any association with the other variables studied (biopsy day, maternal age, male age, duration infertility, cycle length, previous miscarriage, previous live birth, previous cycles IVF, endometrial pattern and diagnosis). Limitations, reasons for caution The retrospective study design limits the generalization of our results but offers a good insight to be validated in prospective trials. Wider implications of the findings: According to our findings, BMI, endometrial thickness the day of the embryo transfer, and the type of endometrial preparation should be considered when transferring an euploid blastocyst. Trial registration number NO APLICA