Lower Cumulative Live Birth Rate Research Articles

Identify high-risk DOR women ≤ 35 years old following assisted reproduction technology through cutoffs of anti-mullerian hormone and antral follicle counts

BackgroundFemales with diminished ovarian reserve (DOR) have significantly lower cumulative live birth rates (CLBRs) than females with normal ovarian reserve. A subset of young infertile patients, whose ovarian reserve is declining but has not yet met the POSEIDON criteria for DOR, has not received the attention it merited. These individuals have not been identified in a timely manner prior to the initiation of assisted reproductive technology (ART), leading to suboptimal clinical pregnancy outcomes. We categorized this overlooked cohort as the “high-risk DOR” group.ObjectiveThe primary aim of this study was to identify high-risk DOR patients through anti-Mullerian hormone (AMH) and antral follicle counts (AFCs).MethodsA total of 10037 young women (≤ 35 years old) who underwent their first initial oocyte aspiration cycle at a single reproductive medicine center were included and further classified into three groups, based on the thresholds for AMH and AFC established through receiver operating characteristic (ROC) analysis and in alignment with the POSEIDON criteria. Two ROC analyses were performed to identify the cutoff values of AMH and AFC to obtain one viable embryo (one top-quality embryo or one viable blastocyst). The cutoffs of ROC were measured by sensitivity and specificity. The primary outcome was the cumulative live birth rate (CLBR) per oocyte aspiration cycle. The secondary outcomes included the number of oocytes retrieved and the number of viable embryos formed. Pearson’s chi-square tests were conducted to compare the clinical outcomes among the three groups. Furthermore, univariate logistic regression analyses were performed to investigate the associations between ovarian reserve and clinical outcomes. All of the above comparisons between the high-risk DOR and NOR were further confirmed by propensity score matching (PSM) (1:1 nearest-neighbor matching, with a caliper width of 0.02).ResultsAccording to the ROC analyses and POSEIDON criteria, the present study identified a population of high-risk DOR patients (1.20 ng/mL < AMH values < 2.50 ng/mL, with 6 ≤ AFC ≤ 10; n = 682), and their outcomes were further compared to those of DOR patients (positive control, AMH values ≤ 1.2 ng/mL, and/or AFC ≤ 5; n = 1153) and of NOR patients (negative control, 2.5 ng/mL ≤ AMH values ≤ 5.5 ng/mL, and 11 ≤ AFC ≤ 20; n = 2649). Patients in the high-risk DOR group had significantly lower CLBRs than those in the NOR group (p < 0.001) but higher CLBRs than those in the DOR group (p < 0.001). Logistic regression further demonstrated that high-risk DOR was associated with a lower likelihood of cumulative live birth chance (OR 0.401, 95% CI: 0.332–0.486, p < 0.001) than NOR was, with a greater likelihood of cumulative live birth chance (OR 1.911, 95% CI:1.558–2.344, p < 0.001) than DOR was. To investigate the effects of embryo development stage, the outcomes of D3 embryos and blastocysts were analyzed separately. Significant differences in pregnancy outcomes were detected only in D3 embryo ET cycles among the three groups (high-risk DOR vs. NOR, all p < 0.05; DOR vs. NOR, all p < 0.05). DOR/high-risk DOR did not influence the pregnancy loss rates or pregnancy outcomes (clinical pregnancy rates and ongoing pregnancy rates) per positive HCG cycle (all p > 0.05). After PSM, the differences in ovarian response and pregnancy outcomes between the high-risk DOR and NOR groups were consistent with the results before PSM.Conclusion(s)Our study revealed that the CLBR of the high-risk DOR patients was significantly lower than that of females with normal ovarian reserve and greater than that of females with DOR. The values of AMH ranging from 1.2 to 2.5 and AFC ranging from 6 to 10 appeared to constitute meaningful thresholds in females with mildly reduced ovarian reserve.

Correlation of adenomyosis features to live birth rates after the first IVF/ICSI treatment, when using the revised Morphological Uterus Sonographic Assessment group definitions.

Data regarding the impact of adenomyosis on the outcomes after invitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment are conflicting. Standardized diagnostic criteria are prerequisites for studying a potential association between adenomyosis and IVF/ICSI treatment outcomes. This study aims to examine the cumulative live birth rate (CLBR) after the first IVF/ICSI treatment in women with or without direct or indirect features of adenomyosis, using the revised Morphological Uterus Sonographic Assessment (MUSA) group definitions. This was a prospective cohort study of 1037 women aged 25-≤39 years, undergoing their first IVF/ICSI treatment between January 2019 and October 2022. The presence of MUSA features of adenomyosis was assessed prior to treatment start. The CLBR after the first IVF/ICSI treatment was 424/1037 (40.9%, 95% CI, 37.9-43.8) in the total cohort. Women with direct features of adenomyosis had lower CLBR, 25/102 (24.5%; 95% CI, 17.5-31.5) than women without, 399/935 (42.7%; 95% CI, 39.5-45.8), p < 0.001. The adjusted relative risk (aRR) for live birth for women with direct features of adenomyosis compared to women without was 0.62 (95% CI, 0.43-0.88), p = 0.007. Direct features were associated with a higher risk of miscarriage after frozen embryo transfer, aRR 2.88 (95% CI, 1.49-5.57), p = 0.002. Women with indirect features had a lower CLBR [50/188 (26.6%, 95% CI, 20.3-32.9)] than women without [399/935, (42.7%, 95% CI, 39.5-45.8)], aRR 0.58 (95% CI, 0.45-0.75), p < 0.001. For features located in the inner myometrium, the aRR for live birth was 0.29 (95% CI 0.11-0.74), p = 0.010 and for the outer myometrium 2.61 (95% CI 1.42-4.8), p = 0.002. An interrupted junctional zone was the single feature that impacted CLBR the most. The presence of direct or indirect MUSA features of adenomyosis correlates to reduced live birth rates in women undergoing their first IVF/ICSI treatment. Features located in the inner myometrium, particularly an interrupted junctional zone, reduced the chance of live birth the most, whereas location in the outer myometrium was associated with higher chances of live birth. Systematic ultrasound examinations should be considered for women scheduled for IVF/ICSI treatment, for adequate counseling on the chances of successful treatment.

Progestin-primed ovarian stimulation

The use of progestins for the prevention of premature ovulation during ovarian stimulation is called progestin-primed ovarian stimulation (PPOS). Response to ovarian stimulation with PPOS and gonadotropin-releasing hormone (GnRH) analogs seem to be similar with the clinically insignificant differences being explained by endocrine characteristics as expected. PPOS has the advantage of oral administration and lower medication cost than GnRH analogs, but the mandatory cancellation of an otherwise possible fresh embryo transfer can render PPOS less cost-effective if a fresh transfer would have been possible. Oocytes collected in PPOS cycles have similar developmental potential, including blastocyst euploidy rates. Frozen embryo transfer outcomes of PPOS and GnRH analog cycles seem similar both in terms of ongoing pregnancy/live birth rates and obstetric and perinatal outcomes. While some studies reported lower cumulative live birth rates with PPOS, they suffer from methodological issues, including arbitrary definitions of cumulative live birth rates. PPOS has been used in all patient types with consistent results and seems a patient-friendly and cost-effective choice when a fresh embryo transfer is not intended.

Analysis of assisted reproductive outcomes for gynecologic cancer survivors: a retrospective study

ObjectiveTo examine the reproductive outcomes of assisted reproductive technology (ART) in gynecologic cancer patients and to assess maternal and neonatal complications.MethodsWomen diagnosed with gynecologic cancer who underwent their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment between 2013 and 2021 at Shanghai Ji Ai Genetics and IVF Institute were included in this study. Infertile women without any history of cancer were matched to the cancer group. The primary outcome was the cumulative live birth rate. Baseline and follow-up data were compared between groups using Student’s t-tests for normally distributed variables and with Chi-square test for categorical variables. A propensity score-based patient-matching approach was adopted to ensure comparability between individuals with and without specific cancer type.ResultsA total of 136 patients with a history of gynecologic cancer and 241 healthy infertile controls were included in this study. Endometrial cancer constituted 50.70% of the cases and cervical cancer constituted 34.60% of the cases. The cancer group exhibited significantly shorter duration of stimulation, lower levels of estradiol, lower number of retrieved oocytes, day-3 embryos, and blastocysts compared to the control group (P < 0.05). The cumulative live birth rate of the gynecologic cancer group was significantly lower than that of the control group (36.10% vs. 60.50%, P < 0.001). Maternal and neonatal complications did not significantly differ between the groups (P > 0.05). The endometrial cancer and cervical cancer groups showed significantly lower cumulative live birth rates than their matched controls (38.60% vs. 64.50%, P = 0.011 and 24.20% vs. 68.60%, P < 0.001, respectively).ConclusionsThese findings highlight the decreased occurrence of pregnancy and live birth in female gynecologic cancer patients undergoing ART, particularly in endometrial cancers and cervical cancers. These findings have important implications for counseling and managing gynecologic cancer patients undergoing ART.

P-582 Analysis of assisted reproductive outcomes for gynecologic cancer survivors: a retrospective study

Abstract Study question Do women diagnosed with gynecologic cancer have worse pregnancy and neonatal outcomes of assisted reproductive technology (ART) ? Summary answer Decreased live birth rate was observed in female gynecologic cancer patients undergoing ART, particularly in endometrial cancers and cervical cancers. What is known already Gynecologic malignancies comprise approximately 13% of female cancer diagnoses, and oncological treatments such as surgery, chemotherapy, abdominal or pelvic radiotherapy, and hormonotherapy may induce infertility, premature ovarian failure, or early menopause, resulting in a loss of reproductive potential. ART has emerged as an important option for cancer patients undergoing treatment, but the reproductive outcomes of ART among cancer survivors remain poorly understood. Limited research exists regarding the impact of a history of gynecologic cancer on reproductive outcomes of ART. Study design, size, duration 136 women diagnosed with gynecologic cancer who underwent their first IVF/ICSI treatment between 2013 and 2021 were retrospectively enrolled in this study. 241 infertile women without any history of cancer were matched to the cancer group. Participants/materials, setting, methods Women diagnosed with gynecologic cancer who underwent their first IVF/ICSI treatment between 2013 and 2021 were included. Infertile women without any history of cancer were matched to the cancer group. The primary outcome was the cumulative live birth rate. A propensity score-based patient-matching approach was adopted to ensure comparability between individuals with and without specific cancer type. Main results and the role of chance A total of 136 patients with a history of gynecologic cancer and 241 healthy infertile controls were included in this study. Endometrial cancer constituted 50.70% of the cases and cervical cancer constituted 34.60% of the cases. The cancer group exhibited significant shorter duration of stimulation, lower levels of estradiol, lower number of retrieved oocytes, day-3 embryos, and blastocysts compared to the control group (P &amp;lt; 0.05). The cumulative live birth rate of the gynecologic cancer group was significantly lower than that of the control group (36.10% vs. 60.50%, P &amp;lt; 0.001). Maternal and neonatal complications did not significantly differ between the groups (P &amp;gt; 0.05). The endometrial cancer and cervical cancer groups showed significantly lower cumulative live birth rates than their matched controls (38.60% vs. 64.50%, P = 0.011 and 24.20% vs. 68.60%, P &amp;lt; 0.001, respectively). Limitations, reasons for caution Our study was limited by the retrospective design in nature and small sample size of its patient cohort. In addition, the effect of cancer treatments was not evaluated specifically in the current study due to the limited number of patients and possible inconsistency in surgical operations. Wider implications of the findings Our study provides data support for further exploration of the effects of endometrial cancer, cervical cancer, and other gynecologic cancers on fertility. Comprehensive ovarian function assessment, detailed counseling, individualized fertility guidance, and close follow-up after ART therapy are recommended for patients with gynecologic malignancy history. Trial registration number Not applicable

P-217 Keep calm and carry on: assessing the effect of below-benchmark vitrified/warmed donor oocyte survival rates in subsequent laboratory and clinical key performance indicators

Abstract Study question When we experience below benchmark donor oocyte survival rates, are the laboratory and clinical outcomes of the recipient cycle affected? Summary answer Donor-oocyte cryo-survival rates below the benchmark (95-100%) result in slightly lower laboratory KPIs, equivalent live birth rates (LBR) and lower cumulative LBR (CLBR) per cycle. What is known already The use of vitrified/warmed donor oocytes allows overcoming many logistic challenges, but it is hindered by the loss of oocytes due to degeneration after warming. The 2012 Vienna Consensus established the benchmark rate of oocyte survival at 95-100%, competency level at &amp;gt; 85%. Results of &amp;lt; 85% cryo-survival are considered below competency, &amp;lt;70% can be considered poor, and &amp;lt;50% very poor. Below-benchmark rates of survival may not only limit the number of donor oocytes for the cycle, but they can also translate into lower per-oocyte cycle KPIs if the lower survival correlates with lower performance of the surviving oocytes. Study design, size, duration We analyzed 12690 vitrified-warmed donor oocyte recipient cycles, encompassing a total 144793 vitrified/warmed donor oocytes, carried out in a network of European private IVF units from 2018-2022. Cycles with PGT-A and spermatozoa from testicular biopsy were excluded. The primary endpoint of the study was the blastocyst utilization rate per 2PN zygote. Secondary endpoints were fertilization rate, live birth rate after the first single blastocyst transfer (SET-LBR) of each cycle, and cumulative LBR (CLBR). Participants/materials, setting, methods In all cases, fertilization was carried out by ICSI, and embryos were cultured to the blastocyst stage at low oxygen tension. Blastocysts with good or fair quality (A, B &amp; C by ASEBIR Criteria) were considered usable (transferred + cryopreserved blastocyts / zygotes). Differences in proportions were analyzed using chi-square and the adjusted odds ratio (OR) was calculated using multivariable logistic regression. Main results and the role of chance Baseline donor and patient characteristics such as age, stimulation duration and dose, total donor oocytes per cycle, male factor, and fresh/frozen/donor spem were compared between groups and adjusted for when necessary. The mean number of warmed oocytes per cycle was 11.4±3.22 with a mean survival rate of 89.2%. More oocytes per cycle were consumed in the lower survival groups, yet the total oocytes available for ICSI was smaller in the below competency, poor and very poor survival groups. There were differences in the proportion of usable blastocysts per zygote amongst the survival rate groups (benchmark: 48.9%; competence: 47.0%, below-competence: 46.0%; poor: 43.6%; very-poor:43.6%, p &amp;lt; 0.001). Fertilization rates also differed between survival groups (benchmark: 76.9%; competence: 76.5%, below-competence: 75.6%; poor: 74.7%; very-poor:75.4%, p &amp;lt; 0.001) The adjusted odds ratio of live birth on the first SET of the cycle was not lower to the benchmark survival group in all the lower survival groups (Benchmark: 40.9%; Competence: OR:0.995; 95%CI:0.971-1.018; below-competence: OR:0.996; 95%CI:0.970-1.023; poor: OR:1.044; 95%CI:1.003-1.086, and very-poor: OR:1.069; 95%CI:0.976-1.170). The CLBR decreased in lower survival groups, with 80.8% for the benchmark survival group, 80.3% (p = 0.539) for competence, 76.2% (p &amp;lt; 0.001) for below-competence, 72.5% (p &amp;lt; 0.001) for poor, and 74.8% (p = 0.056) for very-poor. Limitations, reasons for caution These results are limited to a donor-oocyte population. Wider implications of the findings Lower oocyte-cryo-survival rates resulted in a lower total number of usable blastocysts obtained for the recipient, and consequently, lower CLBR. However, the competence of surviving oocytes is encouraging, with laboratory KPIs in very close range irrespectively of the cohort survival rates, and similar implantation potential of the obtained blastocysts. Trial registration number not applicable

Live birth rate per fresh embryo transfer and cumulative live birth rate in patients with PCOS under the POSEIDON classification: a retrospective study.

Ovarian stimulation (OS) for in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) in women with PCOS often results in multiple follicular development, yet some individuals experience poor or suboptimal responses. Limited data exist regarding the impact of poor/suboptimal ovarian response on pregnancy outcomes in women with PCOS. The aim of this study was to evaluate whether the live birth rate (LBR) per fresh embryo transfer and cumulative live birth rate (CLBR) per aspiration cycle differ in women with PCOS defined by the Patient-Oriented Strategy Encompassing IndividualizeD Oocyte Number (POSEIDON) criteria. A retrospective study involving 2,377 women with PCOS who underwent their first IVF/ICSI cycle at Sun Yat-sen Memorial Hospital from January 2011 to December 2020 was used. Patients were categorized into four groups based on age, antral follicle count, and the number of oocytes retrieved, according to the POSEIDON criteria. The LBR and CLBR were compared among these groups. Logistic regression analysis was performed to assess whether the POSEIDON criteria served as independent risk factors and identify factors associated with POSEIDON. For patients <35 years old, there was no significant difference in the clinical pregnancy rate between POSEIDON and non-POSEIDON patients, whereas POSEIDON patients exhibited lower rates of implantation and live birth. POSEIDON Group 1a displayed lower rates of implantation, clinical pregnancy, and live birth. However, no significant differences were observed in the rates of clinical pregnancy and live birth between POSEIDON Group 1b and non-POSEIDON groups. For patients ≥35 years old, there were no significant differences in the rates of implantation, clinical pregnancy, and live birth between POSEIDON and non-POSEIDON patients. CLBRs were significantly lower in POSEIDON Groups 1 and 2, compared with the non-POSEIDON groups. The levels of body mass index (BMI), follicle-stimulating hormone (FSH), and antral follicle count (AFC) were associated with POSEIDON hypo-response. POSEIDON was found to be associated with lower CLBR, but not LBR per fresh embryo transfer. In patients with PCOS, an unexpected suboptimal response can achieve a fair LBR per fresh embryo transfer. However, CLBR per aspirated cycle in POSEIDON patients was lower than that of normal responders. BMI, basal FSH level, and AFC were independent factors associated with POSEIDON. Our study provides data for decision-making in women with PCOS after an unexpected poor/suboptimal response to OS.

Endometriosis diagnosed by ultrasound is associated with lower live birth rates in women undergoing their first in vitro fertilization/intracytoplasmic sperm injection treatment

ObjectiveTo study the cumulative live birth rate (CLBR) after the first In Vitro Fertilization (IVF) or Intracytoplasmic Sperm Injection (ICSI) treatment in women with or without deep infiltrating endometriosis (DIE) and/or endometrioma diagnosed by transvaginal ultrasonography (TVUS), using the International Deep Endometriosis Analysis (IDEA) group definitions. DesignProspective observational cohort study at a university hospital. SubjectsIn total 1040 subfertile women aged 25- ≤39 years, undergoing their first IVF/ICSI treatment between January 2019 and October 2022. Of these, 234 (22.5%; 95% Confidence Interval (CI), 20.0 – 25.0) women were diagnosed with DIE and/or endometrioma at systematic TVUS prior to starting their treatment. ExposureAll women underwent their first IVF or ICSI treatment. Fresh and/or frozen embryos from the first cycle were used until pregnancy was achieved or no embryos remained. Main Outcome MeasuresCLBR after the first IVF/ICSI cycle in women with or without DIE and/or endometrioma. ResultsThe CLBR after the first IVF/ICSI treatment in the total cohort of women was 426/1040, (41.0%; 95% CI, 38.0 – 44.0). Women with DIE and/or endometrioma had a lower CLBR (78/234, 33.3%; 95% CI, 27.3 – 39.4) compared to women without the disease (348/806, 43.2%; 95% CI, 39.8 – 46.6), p=0.007. The crude relative risk (RR) for cumulative live birth for women with DIE and/or endometrioma was 0.77; 95% CI, 0.63-0.94, and after adjustments were made for age, BMI, s-anti müllerian hormone, stimulation protocol and day for embryo transfer, the adjusted RR was 0.63; 95% CI, 0.48-0.82. There was no difference in the number of retrieved mature oocytes, fertilization rate or good quality embryos between the two groups. ConclusionThe presence of DIE and/or endometrioma diagnosed by TVUS lowers the chance for a live birth in women undergoing their first IVF/ICSI treatment.

Maternal hypercholesterolemia would increase the incidence of embryo aneuploidy in couples with recurrent implantation failure

BackgroundThe association of dyslipidemia with embryo development and pregnancy outcomes is largely unknown, especially in unexplained recurrent implantation failure (uRIF) patients. Here, this study aimed to explore the impact of abnormal blood lipid levels on embryo genetic status and pregnancy outcomes after preimplantation genetic testing for aneuploidy (PGT-A) from a clinical perspective.MethodsThis study retrospectively analyzed 502 patients diagnosed as uRIF. They were divided into four groups according to the levels of cholesterol and triglyceride: nonhyperlipidemia group (NonH group), simple hypercholesterolemia group (SHC group), simple hypertriglyceridemia group (SHC group) and mixed hyperlipidemia group (MixH group). At the same time, patients were divided into non-low HDL-C group and low HDL-C group according to their HDL-C level. The outcomes of embryos genetic testing and pregnancy outcomes after PGT-A was analyzed between groups. Binary logistic regression and/or generalized estimating equation (GEE) model were conducted to investigate the association of different types of dyslipidemia with embryonic aneuploidy rate and cumulative live-birth rate.Results474 women who met the inclusion criteria were divided into four groups: NonH group (N = 349), SHC group (N = 55), SHT group (N = 52) and MixH group (N = 18). Compared with the NonH group, SHC group had a significantly increased rate of embryo aneuploidy [48.3% vs. 36.7%, P = 0.006; adjusted OR (95% confidence interval) = 1.52(1.04–2.22), P = 0.029], as well as a reduced number of good-quality embryos on day 5 or 6 [3.00 ± 2.29 vs. 3.74 ± 2.77, P = 0.033]. The SHC group showed a tendency of a lower cumulative live birth rate (47.0% vs. 40.0%), a lower incidence of good birth outcome (37.2% vs. 34.5%) and a higher risk of clinical pregnancy loss (11.1% vs. 17.9%), but did not reach statistical significance (P > 0.05). The incidences of obstetric or neonatal complications and other adverse events were similar in the four groups. Whether patients have low HDL-C did not differ in pregnancy outcomes.ConclusionsWe found that uRIF women with hypercholesterolemia had an increased proportion of aneuploid embryos and a reduced proportion of high-quality embryos, while different types of hyperlipidemia had no correlation with cumulative live birth rate as well as pregnancy and neonatal outcomes.

P-205 comparison of GnRH antagonist protocol versus progestin-primed protocol in high ovarian responders: a propensity score-matched study

Abstract Study question To compare the clinical outcomes and cost-efficiency between gonadotropin-releasing hormone (GnRH) antagonist and progestin-primed ovarian stimulation (PPOS) protocol in high ovarian responders. Summary answer Comparing with PPOS protocol, GnRH antagonist protocol was associated with shorter time to live birth, higher OHSS rate and less cost in high responders. What is known already For high ovarian responders prone to develop ovarian hyperstimulation syndrome (OHSS), the best option should be the GnRH antagonist, as it has been shown to significantly reduce the incidence of OHSS. By applying ovarian stimulation using the combination of antagonist with agonist trigger and embryos freezing, OHSS can be erased. PPOS protocol in combination with a freeze-all strategy has proved to be a valid alternative to the conventional stimulation protocols. Recent studies showed that comparing with antagonist protocol, a lower cumulative live birth rate (CLBR) was associated with PPOS in general population, with no data available in high responders. Study design, size, duration This was a propensity score-matched retrospective cohort study. From Jan. 2016 to Jan. 2023, 5810 patients with AMH &amp;gt; 3.67ng/ml undergoing IVF treatment with antagonist or PPOS protocol at the Sixth Affiliated Hospital of Sun Yat-sen University were screened. Participants/materials, setting, methods Two-to-one propensity score matching was performed with a caliper of 0.2. After matching, 540 patients in GnRH antagonist group and 270 patients in PPOS group were included. Generalized estimated equation regression was applied to evaluate the impact of independent variables on the CLBR. Main results and the role of chance No significant difference in baseline characteristics was found in two groups. The OHSS (moderate to severe) rate was significantly higher in the GnRH antagonist group than in the PPOS group (7% vs. 3%). The clinical pregnancy rate and live birth rate per transfer were comparable between the two groups. After excluding patients who didn't achieve live birth but had surplus embryos, the CLBR was comparable between the antagonist and PPOS group (67.4% vs. 61.0%; Risk ratio = 1.106; 95% confidence interval [CI], 0.973-1.256, P = 0.109), and the generalized estimated equation regression analysis also showed that protocol selection had no significant impact on CLBR. The average time to live birth (TTLB) in the antagonist group was significantly shorter than the PPOS group (11.45 months vs. 12.13 months, P &amp;lt; 0.05). Besides, the average cost in the antagonist group was about $4933, while it was about $5465 in the PPOS group. Limitations, reasons for caution Although we recruited a large sample size and the sophisticate statistical analysis method, this was a retrospective study with an intrinsic limitation, besides more patients in the PPOS group had surplus embryos than in the antagonist group (24.1% vs. 19.8%). Further prospective RCTs are required to confirm our findings. Wider implications of the findings For infertile patients with high ovarian reserve, the clinical outcomes were comparable between GnRH antagonist and PPOS group. The antagonist group was associated with a shorter TTLB and more cost-effective, while the PPOS was associated with a lower OHSS rate. Trial registration number Not Applicable

Association Between Uterine Volume and In Vitro Fertilization (IVF) Reproductive Outcomes of Infertile Patients with Adenomyosis

To explore the association between uterine volume and in vitro fertilization (IVF) reproductive outcomes of infertile patients with adenomyosis, we performed a retrospective cohort study of infertile patients with adenomyosis who underwent IVF from January 2009 to December 2019 in our clinical center. Patients were divided into five groups according to the uterine volume before the IVF cycle. A line graph was drawn to demonstrate the linear trend of IVF reproductive outcomes with uterine volume. Univariate and multivariate analyses were used to explore the association between uterine volume of adenomyosis patients and IVF reproductive outcomes in first fresh embryo transfer (ET) cycle, first frozen-thawed embryo transfer (FET) cycle, and per ET cycle. Kaplan–Meier curves and Cox regression were conducted to evaluate the association between uterine volume and cumulative live birth. A total of 1155 infertile patients with adenomyosis were included. Clinical pregnancy rate showed no significant correlation with uterine volume in first fresh ET cycle, first FET cycle, and per ET cycle; miscarriage rate showed an upward trend with uterine volume increasement, in which the uterine volume turning point was 8 weeks of gestation; live birth rate showed a downward trend with turning point of 10 weeks of gestation. Subsequently, patients were divided into two groups (uterine volume ≤ 8 weeks of gestation vs. uterine volume > 8 weeks of gestation). Univariate and multivariate analyses showed that patients with a uterus larger than 8 weeks of gestation had a higher miscarriage rate and a lower live birth rate in all ET cycles. Kaplan–Meier curves and Cox regression demonstrated lower cumulative live birth rate in patients with a uterine volume larger than 8 weeks of gestation. IVF reproductive outcome gets worse as uterine volume increases in infertile patients with adenomyosis. Adenomyosis patients with a uterus larger than 8 weeks of gestation had a higher miscarriage rate and a lower live birth rate.

Predicted probabilities of live birth following assisted reproductive technology using United States national surveillance data from 2016 to 2018

As the use of invitro fertilization continues to increase in the United States, up-to-date models that estimate cumulative live birth rates after multiple oocyte retrievals and embryo transfers (fresh and frozen) are valuable for patients and clinicians weighing treatment options. This study aimed to develop models that generate predicted probabilities of live birth in individuals considering invitro fertilization based on demographic and reproductive characteristics. Our population-based cohort study used data from the National Assisted Reproductive Technology Surveillance System 2016 to 2018, including 196,916 women who underwent 207,766 autologous embryo transfer cycles and 25,831 women who underwent 36,909 donor oocyte transfer cycles. We used data on autologous invitro fertilization cycles to develop models that estimate a patient's cumulative live birth rate after all embryo transfers (fresh and frozen) within 12 months after 1, 2, and 3 oocyte retrievals in new and returning patients. Among patients using donor oocytes, we estimated the cumulative live birth rate after their first, second, and third embryo transfers. Multinomial logistic regression models adjusted for age, prepregnancy body mass index (imputed for 18% of missing values), parity, gravidity, and infertility diagnoses were used to estimate the cumulative live birth rate. Among new and returning patients undergoing autologous invitro fertilization, female age had the strongest association with cumulative live birth rate. Other factors associated with higher cumulative live birth rates were lower body mass index and parity or gravidity ≥1, although results were inconsistent. Infertility diagnoses of diminished ovarian reserve, uterine factor, and other reasons were associated with a lower cumulative live birth rate, whereas male factor, tubal factor, ovulatory disorders, and unexplained infertility were associated with a higher cumulative live birth rate. Based on our models, a new patient who is 35 years old, with a body mass index of 25 kg/m2, no previous pregnancy, and unexplained infertility diagnoses, has a 48%, 69%, and 80% cumulative live birth rate after the first, second, and third oocyte retrieval, respectively. Cumulative live birth rates are 29%, 48%, and 62%, respectively, if the patient had diminished ovarian reserve, and 25%, 41%, and 52%, respectively, if the patient was 40 years old (with unexplained infertility). Very few recipient characteristics were associated with cumulative live birth rate in donor oocyte patients. Our models provided estimates of cumulative live birth rate based on demographic and reproductive characteristics to help inform patients and providers of a woman's probability of success after invitro fertilization.

8999 Reproductive Outcomes and Overall Prognosis of Patients with Asherman's Syndrome Undergoing IVF Cycles

<h3>Study Objective</h3> To estimate the impact of Asherman's Syndrome (AS) following hysteroscopic adhesiolysis on short term reproductive outcomes and the time to achieve pregnancy in infertile patients during IVF cycles. <h3>Design</h3> Retrospective cohort study. <h3>Setting</h3> Tertiary university affiliated medical center. <h3>Patients or Participants</h3> Fifty-one infertile patients who were treated for Asherman's syndrome (AS) and underwent IVF cycles (study group). Patients were matched with controls in a 1:1 ratio, according to their age and etiology of infertility (control group). <h3>Interventions</h3> The collected date was obtained from medical records and telephonic survey. <h3>Measurements and Main Results</h3> There was no difference in the mean number of embryo transfer per patient between the two groups (4.9 ±4.6 vs. 6.22 ±4.3, p=0.78). The mean endometrial thickness before embryo transfer was significantly higher among women in the control group (8.7 ±1.8 vs. 6.95±1.7, respectively, p=0.001). Women with AS had significantly lower cumulative live birth rate and significantly higher miscarriage rate as compared to women in the control group (23.5% vs 56.8, p=0.001 and 41% vs. 15.6%, p=0.008 accordingly). The mean endometrial thickness was significantly higher among women with AS who had live birth (8.2 (±1.4) 6.9 (±1.2), p=0.001). The Overall time to conception was significantly longer among with AS (407.962 ±74.7 Vs 785.6 <h3>Conclusion</h3> AS has an impact on the reproductive potential in infertile patients following hysteroscopic adhesiolysis. Endometrial thickness was shown to be an important predictor for live birth among women with AS that utilizing IVF.

Effect of Female and Male Body Mass Index on Cumulative Live Birth Rates in the Freeze-all Strategy.

The impact of parental overweight/obese on cumulative live birth rate in in vitro fertilization/intracytoplasmic sperm injection using a freeze-all strategy is still unknown. To explore the effect of parental body mass index (BMI) on cumulative live birth rate (CLBR) in a freeze-all strategy over 1.5 years. This was a retrospective study in a tertiary care academic medical center; 23 482 patients (35 289 frozen-thawed embryo transfer cycles) were divided into 4 groups according to Asian BMI classification. The main outcome measure was CLBR. Female overweight/obesity had a lower tendency in CLBR (groups 1-4: optimistic: 69.4%, 67.9%, 62.3%, and 65.7%; conservative: 62.9%, 61.1%, 55.4%, and 57.6%) and prolonged time (groups 1-4: 11.0, 12.2, 15.9, and 13.8 months for 60% CLBR in the optimistic method; 8.7, 9.5, 11.7, 11.0 months for 50% CLBR in the conservative method). The same trend to a lesser extent was also observed in male BMI groups. When combining parental BMI, "parental overweight/obesity" had lower CLBR and longer time for reaching CLBR >50% (optimistic: 4.5 months for 60% CLBR; conservative: 3 months for 50% CLBR), followed by "only female high BMI" (optimistic: 2.1 months for 60% CLBR; conservative: 1.7 months for 50% CLBR), while "only male high BMI" had no influence. Our results showed the importance of parental BMI, female BMI, and male BMI on the 1.5-year CLBR using a freeze-all strategy; the time to reach the CLBR (60% in optimistic, 50% in conservative) for overweight and obese patients was several months, but it is not as long as losing weight.

O-014 How effective is oocyte cryopreservation?

Abstract text The challenge of cryopreserve, store for prolonged period, and successfully implant the female gamete is nowadays feasible thanks to vitrification. The technology that was initially validated in oocyte recipients is currently applied to a vast population, including women at risk of losing their ovarian function due either to iatrogenic causes as occurs in cancer patients, or due to the natural depletion of the ovarian reserve as a result of age related fertility decline. That is the case of a growing population of women who wish to postpone childbearing and decide on oocyte vitrification as a means of fertility preservation (FP). At present, there is a growing body of evidence regarding the use of vitrified oocytes by many women under different indications, which makes it possible to evaluate the approach from different scenarios. So that vitrification can be evaluated in terms on survival rates, embryo development and the rate at which vitrified oocytes develop into live-born children in IVF cycles using vitrified oocytes which were initially stored due to different reasons. The effects of vitrification at the subcellular level and its impact on oocyte competence is of interest in the evaluation of the efficacy of the technology. Some studies have indicated that vitrification may affect ultrastructure, reactive oxygen species (ROS) generation, gene expression, and epigenetic status. However, it is still controversial whether oocyte vitrification could induce DNA damage in the oocytes and the resulting early embryos. Recent studies show that oocytes survival and clinical outcome after vitrification can be impaired by patients’ age and the clinical indication or the reason for vitrification. These studies show that age at oocyte retrieval strongly affects the survival and reproductive prognosis. In our experience, oocyte survival, pregnancy and cumulative live birth rates are significantly higher when patients are aged 35 years or younger versus patients older than 35 years at oocyte retrieval. Therefore, elective-FP patients should be encouraged to decide at young ages to significantly increase their chances of success. There is also evidence that the reason for vitrification is associated to the success rates. Poorer reproductive outcome was reported in cancer patients, low responders and endometriosis patients when compared to healthy women in age matching groups. Moreover, there are certain individualities linked to specific populations, as occurs when endometriosis patients had cystectomy earlier than the oocyte retrieval for FP. These women achieved lower success rates as compared to non-operated age matching counterparts. In this case, the lower cumulative live birth rates observed in operated women are, most probably, due to the smaller number of oocytes available, as a consequence of the detrimental effect of the surgery on the ovarian reserve. In this regard, several reports show that the number of oocytes available per patient is another variable closely related to the outcome in all populations using vitrified oocytes after FP. Thus, a significant improvement in the cumulative live birth rates can be achieved by adding a few oocytes, especially in healthy young patients. Different populations using vitrified oocytes under several indications achieve differential results in terms of pregnancy rates, when calculated in overall. Nonetheless, when the calculations for the cumulative probability of achieving a baby are made according the number of oocytes used per patient belonging to the same group of age, the results become comparable between different populations, as shown by the comparison between elective freezers versus endometriosis patients. Undoubtedly, vitrification can be recognized as one of the latest brakethrough in the ART field, but certainly the next step forward would be the successfull automatization of the vitrification and warming processes to achieve fully consistency among different laboratories.

P–787 Impact of delaying ART to promote weight loss: a large multicentre study accounting for the combined effect of female/male age and body mass index (BMI)

Abstract Study question Is postponing the start of ART (to promote a reduction in female BMI) beneficial for cumulative live birth rates (CLBR) when accounting for the female/male ageing this delay will cause? Summary answer Postponing ART treatment in one year to promote female weight loss could be detrimental in women of advanced maternal age (AMA, &amp;gt;35 years-old). What is known already Overweight/obese couples are frequently encouraged to lose weight prior to infertility treatment to enhance ART outcomes. However, a meaningful weight loss is often difficult to achieve for these couples, frequently taking at least one year to accomplish. Given that both female and male ageing are also important for ART success, we were interested in understanding the combined impact on CLBR of BMI reduction and ageing following a one-year delay. Study design, size, duration A retrospective study including patients performing their first ART cycle using autologous gametes between 2013–2018 in one of 39 participating ART centres. Only GnRH antagonist cycles were included (n = 14260). CLBR was the primary outcome. Secondary outcomes included time-to-pregnancy, birthweight and gestational age. Participants/materials, setting, methods Patients were subdivided according to female BMI (Kg/m2) in either underweight (&amp;lt;18.5), normal-weight (18.5–24.9), overweight (BMI 25.0–29.9 kg/m2) and obese (≥30 kg/m2). Meaningful and extreme weight loss were defined as a reduction from obesity to either overweight or normal-weight, respectively. We performed multivariable regression analysis to account for potential confounding. Main results and the role of chance Overweight (36.8%) and obese (33.0%) women had significantly lower CLBR when compared to the underweight (42.6%) and normal-weight (41.4%). When assessing the confounder-adjusted net-effect of male/female age and BMI, the predicted benefit of promoting a meaningful BMI reduction was lower than the estimated hindrance due to male/female ageing as soon as women reached AMA (n = 8365, 58.6%). This absence of benefit was especially important in women &amp;gt;38 years-old, in which even extreme weight-loss did not compensate for the age-related reduction in CLBR caused by the one-year delay. Moreover, male weight-loss failed to provide any additional benefit when accounted for in the regression models. Finally, obesity was also associated with a modest but statistically significant one-month delay in time-to-pregnancy and a 96.1 g (95% confidence interval: 39.9–152.4) increase in birth weight. The diagram of predicted outcomes presented in this study may serve as a useful tool to counsel patients before treatment, namely when recommending treatment postponement to promote short-term (i.e. 3–6 months) or long-term (i.e. 1 year) weight loss. Limitations, reasons for caution Caution is recommended when extrapolating these results into everyday practice owing to the retrospective nature of the study and the fact that only GnRH antagonist cycles were included. Wider implications of the findings: Patients are frequently confronted with the dilemma to either postpone treatment (and promote weight loss) or start treatment immediately (to avoid further ageing). Our results seem to show that women in AMA may have hindered CLBR if recommended to delay treatment even if the desired weight loss is ultimately achieved. Trial registration number Not applicable

Parameters of poor prognosis in preimplantation genetic testing for monogenic disorders

Abstract STUDY QUESTION What is the likelihood of success of a single cycle of preimplantation genetic testing for monogenic disorders (PGT-M), measured as the cumulative live birth rate (CLBR) and based on various patient demographics? SUMMARY ANSWER For all women aged ≤40 years, the CLBR was at least 10% when the number of oocytes was ≥7 (range 10–30%) or was at least 5% when the number of oocytes was ≥3 (range 5–17%). WHAT IS KNOWN ALREADY The number of oocytes is significantly associated with the number of embryos for genetic testing and the clinical outcome in PGT-M. Embryos diagnosed as affected or embryos that remain without diagnosis cannot be used for embryo transfer. The size of the group of embryos non-suitable for transfer varies between 25% and 81%, depending on the indication. Thus, PGT-M is more likely to be more severely impacted by suboptimal ovarian response, poor fertilization and suboptimal embryo development than conventional IVF/ICSI schemes without PGT. STUDY DESIGN, SIZE, DURATION This was a single-centre retrospective comparative cohort study, of cycles between January 2011 and December 2015. A total number of 2265 PGT-M cycles were compared to 2833 conventional ICSI cycles. The principal aim of our study was the identification of the parameters of poor CLBR in couples undergoing PGT-M using multiplex short tandem repeat (STR) markers on blastomere biopsy DNA. The secondary aim was to compare the parameters of poor CLBR of the PGT-M population to those of couples undergoing ICSI without PGT. PARTICIPANTS/MATERIALS, SETTING, METHODS The baseline characteristics of the PGT-M group were compared to the conventional ICSI group. A multiple regression analysis was applied to account for the following potential confounding factors: female age, number of previous ART cycles, number of oocytes/suitable embryos for transfer and dosage of gonadotrophins used for ovarian stimulation. MAIN RESULTS AND THE ROLE OF CHANCE The PGT-M group was younger (female age 32.0 vs 34.5 years), had a higher number of previous ART cycles (1.1 vs 0.9 cycles) and used more gonadotrophins (2367 vs 1984 IU). Per cycle, the PGT-M group had more retrieved oocytes (11.8 vs 8.3 oocytes), fewer suitable embryos for transfer (1.7 vs 2.8 embryos) and a lower CLBR (29.4% vs 35.0%). Multiple regression analysis showed that the CLBR in the PGT-M group was significantly influenced by female age, the number of previous ART cycles, the number of oocytes and the dose of ovarian stimulation. In both groups, the predicted CLBR increased with increasing numbers of oocytes and suitable embryos. At least two retrieved oocytes or one embryo per single PGT-M cycle could confer an estimated CLBR above 10%. By assessing female age and the number of retrieved oocytes together, it was shown that for all women aged ≤40 years, the predicted CLBR per single PGT-M cycle was ≥10% when the number of oocytes was ≥7 or was ≥5% when the number of oocytes was ≥3. LIMITATIONS, REASONS FOR CAUTION Despite the large sample size, the findings are confined by limited confounder adjustment and the lack of specific PGT-M comparators. WIDER IMPLICATIONS OF THE FINDINGS This study aimed to describe the likelihood of success of PGT-M treatment, measured as CLBR, based on various patient demographics. In a PGT-M program, couples need to be informed of the prognosis more specifically when it is futile. The table of predicted CLBRs presented in this study is a useful tool in counselling PGT-M couples for making reproductive choices. STUDY FUNDING/COMPETING INTEREST(S) No funding was required and there are no competing interests. TRIAL REGISTRATION NUMBER N/A.

Assisted reproductive technology outcomes in women with a chronic viral disease.

The aim of this study was to evaluate the cumulative live birth rate in women undergoing in-vitro fertilization/intracytoplasmic-sperm-injection (IVF/ICSI) according to the type of chronic viral infection [HIV, hepatitis-B virus (HBV) and hepatitis-C virus (HCV)]. A cohort study. A tertiary-care university hospital. Women with a chronic viral illness HIV, HBV or HCV- were followed until four IVF/ICSI cycles had been completed, until delivery or until discontinuation of the treatment before the completion of four cycles. The primary outcome was the cumulative live birth rate after up to four IVF/ICSI cycles. A total of 235 women were allocated to the HIV-infected group (n = 101), the HBV-infected group (n = 114) and the HCV-infected group (n = 20). The cumulative live birth rate after four cycles was significantly lower in the HIV-infected women than in those with HBV [39.1%, 95% confidence interval (95% CI): 17.7-60.9 versus 52.8%, 95% CI: 41.6-65.5, respectively; P = 0.004]. Regarding the obstetrical outcomes, the mean birth weight was lower in the HIV-infected women than in those with HBV or HCV. Multivariate analysis indicated that the age, the anti-Müllerian hormone and the number of cycles performed were significantly associated with the chances of a live birth. HIV-infected women had lower cumulative live birth rate than women with chronic hepatitis, and this was due to less favourable ovarian reserve parameters. These findings underscore the need to better inform practitioners and patients regarding fertility issues and the importance of early fertility assessment. However, larger studies are necessary to gain more in-depth knowledge of the direct impact of HIV on live birth rates.

The association between antidepressant use and assisted reproductive technology (ART) treatment in Danish women: A national registry-based cohort study

ObjectiveTo investigate (1) if antidepressant use among women in assisted reproductive technology (ART) treatment and among women without ART treatment influences cumulative live birth rates (CLBR) and number of initiated treatment cycles per woman, (2) whether women undergoing ART treatment are at higher risk of initiating use of antidepressants compared to women not having undergone ART, (3) if mothers after ART treatment have higher risk for postpartum use of antidepressants after ART treatment compared to mothers not having used ART treatment. Study designA Danish nation-wide register-based cohort study including all women in ART treatment between 1995 through 2009 and an age-matched comparison group of women not having initiated ART treatment. In both groups, women had no previous children before study entry. The women were followed from time of initiating first ART treatment until time of permanent emigration (> 6 months), date of death, or end of follow-up by 31st of December 2009. Chi-square test was used to assess whether observed differences in CLBR between groups were significant. Adjusted incidence rates (IR) and incidence rate ratio (IRR) with 95 % confidence interval (CI) were calculated using Poisson regression analysis. The main outcome measures were: CLBR, number of initiated ART treatment cycles and IRR of initiating antidepressant use. ResultsWomen using antidepressants before, during or after ART treatment were significantly older, had a lower CLBR and a lower mean number of initiated ART treatment cycles compared to women in ART treatment with no use of antidepressants. No significant difference was found in the incidence of initiating antidepressant use between women in ART treatment and the comparison group. However, when comparing only women with a live birth, significantly more women in ART treatment initiated antidepressant use in the postpartum period (adjusted incidence rate ratio (IRR) = 2.56 (95 % CI 1.98−3.30; p < 0.001)). ConclusionGenerally, women undergoing ART treatment are not at higher risk of initiating use of antidepressants compared with an age-matched comparison group not treated with ART. However, women with antidepressant medication use prior to ART initiate fewer ART treatments and have lower CLBR. Even though it has not been possible to adjust for all relevant confounders and our follow-up period only runs until the end of 2009, we still believe the results of this study to be highly relevant. According to our study, clinicians should be aware that women conceiving after ART treatment might experience an increased level of psychological strain during the postpartum period compared to mothers who conceived without ART.

Status of racial disparities between black and white women undergoing assisted reproductive technology in the US

BackgroundNumerous studies have demonstrated substantial differences in assisted reproductive technology outcomes between black non-Hispanic and white non-Hispanic women. We sought to determine if disparities in assisted reproductive technology outcomes between cycles from black non-Hispanic and white non-Hispanic women have changed and to identify factors that may have influenced change and determine racial differences in cumulative live birth rates.MethodsThis is a retrospective cohort study of the SARTCORS database outcomes for 2014–2016 compared with those previously reported in 2004–2006 and 1999/2000. Patient demographics, etiology of infertility, and cycle outcomes were compared between black non-hispanic and white non-hispanic patients. Categorical values were compared using Chi-squared testing. Continuous variables were compared using t-test. Multiple logistic regression was used to assess confounders.ResultsWe analyzed 122,721 autologous, fresh, non-donor embryo cycles from 2014 to 2016 of which 13,717 cycles from black and 109,004 cycles from white women. The proportion of cycles from black women increased from 6.5 to 8.4%. Cycles from black women were almost 3 times more likely to have tubal and/or uterine factor and body mass index ≥30 kg/m2. Multivariate logistic regression demonstrated that black women had a lower live birth rate (OR 0.71;P < 0.001) and a lower cumulative live birth rate for their initial cycle (OR 0.64; P < 0.001) independent of age, parity, body mass index, etiology of infertility, ovarian reserve, cycle cancellation, past spontaneous abortions, use of intra-cytoplasmic sperm injection or number of embryos transferred. A lower proportion of cycles in black women were represented among non-mandated states (P < 0.001) and cycles in black women were associated with higher clinical live birth rates in mandated states (P = 0.006).ConclusionsDisparities in assisted reproductive technology outcomes in the US have persisted for black women over the last 15 years. Limited access to state mandated insurance may be contributory. Race has continued to be an independent prognostic factor for live birth and cumulative live birth rate from assisted reproductive technology in the US.