Positive β-hCG Research Articles

P–264 Clinical relevance of re-expansion after blastocyst thawing

Abstract Study question Are there any differences in clinical outcomes after SET of re-expanded versus non-re-expanded blastocysts? Summary answer The transfer of re-expanded thawed blastocysts is associated with improved clinical outcomes. What is known already Improvements in embryo culture conditions, endometrial receptivity protocols and vitrification as a revolutionary cryopreservation technique have allowed the expansion of blastocyst stage transfers (Lieberman and Tucker, 2006; Stanger et al., 2012; Rienzi et al., 2017), increasing clinical pregnancy and implantation rates in IVF cycles. The re-expansion of thawed blastocyst at the time of transfer has been considered as a good prognosis factor, but not always thawed embryos re-expand. To evaluate the relevance of this event, we compared the clinical results of the re-expanded embryos versus the collapsed ones after their thawing and transfer. Study design, size, duration A total number of 1.125 frozen-thawed blastocyst transfers were included in this retrospective observational study between January 2018 and December 2020. Seven hundred and eighty-six thawed blastocyst were fully expanded at the time of the transfer and 339 thawed blastocysts were non-re-expanded when they were transferred. Participants/materials, setting, methods 1.125 single frozen-thawed blastocyst embryo transfer (SET) cycles (802 from donated and 319 from autologous oocytes) were divided in two groups (re-expanded vs non-re-expanded). Positive beta human chorionic gonadotrophin (bHCG), pregnancy rate (PR), early miscarriage rate (EMR) and live birth rate (LBR) were compared between the two groups. Blastocysts were thawed using an Irvine Scientific® Thaw kit, Irvine Scientific® and were transferring in culture medium (Global® Total® LP, CooperSurgical®). Main results and the role of chance During 2018, 190 re-expanded blastocyst and 94 non-re-expanded were transferred. Statistical significant differences were found in the percentage of positive bHCG (48.4% vs 30.9%, p < 0,0048) and PR (39.5% vs 25.5%, p < 0,0203), respectively. In 2019, statistical differences were found in the LBR between 307 re-expanded blastocyst and 124 non-re-expanded (30.6% vs 12.9%; p < 0,00001). Differences were also found in positive bHCG (50.2% vs 21.8%, p < 0,00001) and PR (40.7% vs 15.3%, p < 0,00001), respectively. Finally, in 2020, 289 re-expanded blastocyst and 121 non-re-expanded were transferred, and significant differences were obtained in the percentage of positive bHCG (46.8% vs 22.3%, p < 0,00001) and PR (32.9% vs 15.7%, p < 0,00001), respectively. Globally, all the variables analysed were statistically significant in favour of the re-expanded embryo group: positive bHCG (48.7% vs 24.5%; p < 0,00001), PR (37.5% vs 18.3%; p < 0,00001) and LBR (20.1% vs 9.5%; p < 0,00001), except for EMR. Limitations, reasons for caution The inherent limitations to a retrospective design. Larger studies are warranted in order to reach robust conclusions on the subject. Wider implications of the findings: Transfer of re-expand blastocyst could be a positive indicator of clinical outcomes. In case of non-re-expand embryos, transfer of two could be reasonable. Trial registration number NONE

P–209 Artificial collapse of human expanded blastocysts protects the quality of embryos during vitrification/warming procedure

Abstract Study question Does artificial collapse of human blastocysts before vitrification affect the post warming quality of embryos and/or the reproductive outcome? Summary answer This study suggests that artificial collapse with laser pulse before vitrification significantly benefits blastocyst quality post-warming without improving reproductive outcome. What is known already The efficiency of vitrification of blastocysts can be influenced by various factors, such as the stage of the expansion and the quality of the embryos. Expanded blastocysts seem to be more sensitive and prone to cryo-injury during vitrification because of the large amount of blastocoelic fluid which may cause insufficient dehydration. Artificial collapse (AC) with micro-needles or with laser pulse can improve the vitrification procedure and protect the expanded blastocysts from cryoinjuries by reducing the fluid of the blastocoel. Study design, size, duration This prospective randomized study was performed at Embryolab Fertility Clinic, in Thessaloniki, Greece between July 2020 and November 2020 and included 94 ICSI treatments with no fresh embryo transfer. Patients with more than 4 blastocysts were randomized and allocated to the study (AC) group or control group. Randomization list was created by a computer-based program. The embryos were vitrified at the blastocyst stage and the best 1–2 embryos were transferred in a subsequent cycle. Participants/materials, setting, methods Patients were divided in two groups: AC group (n = 46) where 1 or 2 best expanded blastocysts were artificially collapsed by a laser pulse before vitrification and control group (n = 48) where the corresponding best expanded embryos remained untreated before vitrification. The embryos were graded according to Gardner’s criteria and vitrified using open system. Quality of embryos, pregnancy rate and clinical pregnancy rate from the first warming cycle were the parameters that were analyzed using z-test. Main results and the role of chance The analyzed embryos were in total 171, 85 in the AC group and 86 in the control group. The day 5 embryos in each group were 6.89 (±3.41) and 6.50 (±3.38) and the number of embryos per embryo transfer was 1.85 (±0.36) and 1.79 (±0.41) respectively. Cryoinjury was determined as the presence of degenerated cell in ICM or TE. In the AC group cryo-injury was significantly lower than in the control group [31.11% with at least 1 embryo per embryo transfer and 52.08% respectively (p = 0.0356), 6.67% with cryo-injury in both embryos and 14.58% respectively (p < 0.0001), 8.89% with cryo-injury in ICM and 10.42% respectively (p < 0.0001), 15.56% with cryo-injury in trophectoderm and 27.08% respectively (p < 0.0001), and 6.67% with cryo-injury in both ICM and trophectoderm and 12.50% respectively (p < 0.0001)]. Pregnancy rate (positive b-hcg) was not significantly different between the two groups (62.22% in AC group and 76.09% in control group, p = 0.1479), nor was the clinical pregnancy rate (52.38% and 60.87% in AC and control group respectively, p = 0.4208). Limitations, reasons for caution The number of cases included in this study was limited and the live birth rate was not yet available. More prospective randomized studies are needed in order to validate the benefit of artificial collapse before the vitrification procedure. Wider implications of the findings: Laser artificial Collapse does not compromise expanded blastocyst quality, on the contrary it seems to reduce the amount of cryoinjury observed post warming. Whether it can improve the reproductive outcome, remains to be examined in larger scale studies. Trial registration number Not applicable

P–672 Higher pregnancy outcomes in patients undergoing embryo transfer-under hormonal replacement therapy where an individualised Progesterone supplementation was applied on the day of β-hCG

Abstract Study question Does progesterone-supplementation (PS) from the day of β-hCG assessment improve pregnancy rates in embryo transfer-under hormonal replacement therapy (ET-HRT) in patient with Progesterone (P)<10.6 ng/mL? Summary answer Reduced P on the β-hCG day is associated with lower pregnancy-rates and higher miscarriage-rate. PS from the same day showed significant increase of reproductive outcomes. What is known already Up until now, in ART, very little has been done to understand whether the P intake should be personalized during the luteal phase. Most recent studies on the topic showed that low P levels on the day of ET-HRT or on the day before are associated with decreased pregnancy rates; however, when low P values are supplemented from the day before embryo-transfer (ET), similar results to cases with adequate P are reported. Nevertheless, little is known about the association between low P level, on the day of β-hCG (P- β-hCG) and PS from this day in ET-HRT, and pregnancy outcomes. Study design, size, duration This is a single centre, cohort, retrospective study conducted at a university-affiliated fertility centre between January 2018 and June 2020 where PS took place from the day of positive β-hCG determination when P < 10.6 ng/mL. In total 789 ET-HRT cycles were analysed of which 239 were performed in both fresh and frozen heterologous ET-HRT (het-ET), 336 in homologous ET-HRT (hom-FET) and 214 in euploid ET-HRT (eu-FET) after preimplantation genetic testing for aneuploidies IVF cycles (PGT-A). Participants/materials, setting, methods Women undergoing ET-HRT with normal P (>10.6ng/mL) on the day before ET were screened for P on the day of β-hCG. All women received vaginal P 200 mg/8 hours for the second part of HRT. PS was performed by adding P to the HRT when P- β-hCG was considered low (<10.6 ng/mL). Primary outcome: ongoing-pregnancy-rate (OPR); secondary outcome: miscarriage-rate (MR). Both were evaluated by considering PS on the day of β-hCG as a categorical variable. Main results and the role of chance Patients characteristics were comparable between groups (het-ET, hom-FET and eu-FET) although significantly lower body mass index was found when P- β-hCG>10.6 ng/mL compared to the subgroup with P- β-hCG<10.6 ng/mL and no PS (p = 0.012). Overall clinical pregnancy rate was 52.1% with no-significant differences between groups (48.5% in het-ET, 52.9% in hom-FET and 54.7% in eu-FET). P- β-hCG was considered as adequate in 75.7% (311/411) ET-HRT with positive β-hCG and low in 24.3% (100/411), with no differences between groups. In case of positive β-hCG and P- β-hCG >10.6 ng/mL, OPR was 83.6% and MR was 16.4%, with no-significant differences between groups. Among the 100 low P- β-hCG, 80 ET-HRT received PS. In this subgroup OPR was 96.2% and MR was 3.8%, with no-significant differences between groups. In 20 out of 100 ET with P- β-hCG <10.6 ng/mL, no PS was added for different reasons. This group showed the lowest OPR (30%) and the highest MR (70%), again with no between-group differences according to het-ET, hom-FET or eu-FET. Miscarriage rate was significantly higher (p < 0.001) when P- β-hCG was <10.6 ng/mL and no PS was added to HRT compared to P- β-hCG <10.6 ng/mL but with PS, and also compared to the P- β-hCG >10.6 ng/mL group. Limitations, reasons for caution The main limitation of the study is due to its retrospective nature and the small sample of patients with P- β-hCG<10.6 ng/mL that was not supplemented. Furthermore, the cut-off of P- β-hCG was arbitrarily decided upon previous studies, and lastly different routes of administration were considered for the PS. Wider implications of the findings: The results of this study showed that individualization of Progesterone supplementation in ET-HRT may be a crucial turn point in order to increase the pregnancy rates and decrease the miscarriage rates. An adequate PS should be considered in case of low P- β-hCG levels for both het-ET, hom-FET and eu-FET. Trial registration number Not applicable

P–550 Clinical outcomes of mosaic embryos are similar between young and older women

Abstract Study question Are there differences in the clinical outcomes of mosaic embryos depending on the female age? Summary answer Clinical outcomes of mosaic embryo transfers are similar regardless female age. What is known already Chromosomal abnormalities are common in embryos analyzed in preimplantation genetic testing for aneuploidy (PGT-A) cycles. Mosaicism (the presence of two or more chromosomally distinct cell lines) is a usual event in embryos derived from IVF cycles. Several studies show that mosaic embryos have reduced potential to reach term, compared to euploid embryos. The factors affecting the implantation potential and development of mosaic embryos are controversial. Recently, Victor et al. (2019) argued that mosaic blastocysts generated at younger ages show better outcomes compared to older ages. The aim of this study was to test this hypothesis in our centre. Study design, size, duration A total of 136 mosaic embryos from patients undergoing PGT-A cycles from May 2014 to October 2020 were retrospectively analyzed in this study. The blastocyst trophoectoderm biopsies of day 5 and 6 were analysed by aCGH (n = 47, 30.1%) and NGS (n = 109, 69.9%). An embryo was considered mosaic when the percentage of aneuploid cells were 25–50% in aCGH and 20–50% in NGS. Only single embryo transfer cycles were included in the analysis. Participants/materials, setting, methods Embryo analysis were performed using Agilent SurePrint G3 8x60K CGH microarrays or Veriseq NGS (Illumina), with previous whole genome amplification. We evaluated if clinical results of mosaic embryos transfers in IVF cycles were correlated with female age. The main outcome measures were β-hCG, implantation rate and ongoing pregnancy rate. β-hCG was measured in blood 14 days after the embryo transfer and was considered positive when it was >2 mUI/ml.The statistical analysis was performed with SPSSv20.0. Main results and the role of chance A total of 136 mosaic embryos were included in this study. Overall, we evaluated factors affecting embryo mosaicism implantation potential. Neither the percentage of mosaicism nor the segmental mosaicism were related to mosaic embryo implantation, pregnancy and ongoing pregnancy rates. To evaluate the impact of female age in clinical outcomes, we established two different groups depending on whether mosaic blastocysts were generated from oocytes retrieved at young maternal ages (≤35 years; n = 62) or at older ages (>35years; n = 74). No differences were found between groups. Nonetheless, to reduce bias, embryo quality, percentage of mosaicism, segmental mosaicism and whether the transferred embryo was frozen or fresh were included as confounding factors. The rate of positive β-hCG was similar between groups: 45.2% in ≤ 35y group vs 54.1% in > 35y (p = 0.476). The implantation rate was also similar: 30.6% vs 39.2%% (p = 0.855), respectively. Furthermore, the ongoing pregnancy rate was higher in the >35y group (35.1%), compared to the ≤35y group (19.4%) without reaching statistically significant differences (p = 0.245). Limitations, reasons for caution The sample size is a limitation. aCGH test and a different definition for mosaic embryo in terms of percentage of abnormal cells was employed in this study compared to Victor et. al. (2019) study. Larger prospective studies should evaluate the impact of maternal age in the outcome of mosaic embryos. Wider implications of the findings: Our results challenge that female age is associated with clinical outcomes after the transfer of mosaic embryos. Comparable results were obtained in young and older women. Therefore, in the absence of euploid embryos, mosaic embryos might be considered for transfer and similar outcomes are expected regardless of the maternal age. Trial registration number Not applicable

A Case Series of Neglected Pregnancies at the Time of Bariatric Surgery

The aim of this study was to describe three neglected pregnancy at the time of bariatric surgery (BS) who had negative pregnancy test before surgery and underwent single-anastomosis gastric bypass surgery in obesity clinic in Rasoul-e-Akram Hospital, Iran University of Medical Sciences, Tehran, Iran. The first case was a 38 years old woman with BMI of 47.1 suffering from nausea and vomiting one month after surgery that medical treatment did not work and it was found positive βHCG test as and 13W + 6D fetus in sonography. The second case was a 30 years old woman with BMI of 46.2 suffering uterus bleeding four months after surgery. The third case was a 32 years old woman with BMI of 44.6 with suffering from resistant nausea and vomiting, epigastric pain, and delayed mense three month after surgery. These cases show the necessity of βHCG test at the time of bariatric surgery for childbearing females.

Individual culture leads to decreased blastocyst formation but does not affect pregnancy outcomes in the setting of a single, vitrified-warmed euploid blastocyst transfer.

To evaluate embryology and pregnancy outcomes following individual and group embryo culture in the setting of contemporary laboratory practices and freeze-all cycles. Patients underwent ovarian stimulation followed by intracytoplasmic sperm injection (ICSI). Embryos proceeded through individual culture and then underwent preimplantation genetic testing for aneuploidy (PGT-A) via trophectoderm biopsy. In a subsequent cycle, participants underwent single embryo transfer of a vitrified-warmed, euploid embryo. Outcomes were compared to controls undergoing group culture during the same time frame. The Mann-Whitney U test and logistic regression models were utilized. Outcomes were assessed for 144 patients whose embryos underwent individual culture and 449 controls whose embryos underwent group culture. There were no significant differences in fertilization rates between groups (81.7% for individual culture vs. 84.1% for group culture, p = 0.22). However, individual culture was associated with a decreased rate of blastocyst formation compared to group culture (43.5% vs. 48.5%, p < 0.01). Following single, vitrified-warmed euploid blastocyst transfer, there were no significant differences between individual culture and group culture, respectively, in rates of positive βhCG (81.9% vs. 81.5%, p = 0.91), sustained implantation (63.9% vs. 65.0%, p = 0.80), biochemical miscarriage (16.7% vs. 12.3%, p = 0.18), or clinical miscarriage (1.4% vs. 4.2%, p = 0.13). While individual culture appears to negatively impact the rate of usable blastocyst formation compared to group culture, there were no significant differences in pregnancy outcomes following transfer of a single, vitrified-warmed euploid blastocyst.

Relationship between serum progesterone levels at the day before progesterone suppository administration and pregnancy rate in embryo transfer cycles

Introduction: Given the importance of assisted reproductive therapies and achieving a pregnancy leading to live birth, as well as the importance of the used treatments and the various studies which have been performed so far, this study was performed with aim to evaluate the relationship between endometrial pattern and serum progesterone levels at the day before the onset of progesterone suppository in embryo transfer cycles in women referred to Infertility Center of Zahedan. Methods: This cross-sectional study was performed on 50 women who had undergone IVF for any reason and their embryos were frozen in infertility center of Zahedan University of Medical Sciences in 2019. The patients were treated with progesterone suppository 400 mg at morning and 400 mg at evening intra rectally. Demographic data, endometrial pattern and thickness ultrasound, serum progesterone level at the day before the onset of progesterone suppository and serum BHCG levels 14 days after embryo transfer were recorded. Data were analyzed by SPSS statistical software (version 24) and Chi-square and Mann-Whitney tests. P<0.05 was considered statistically significant. Results: IVF outcome was positive in 13 cases (26%). 23 patients (46%) had homogenous endometrial pattern and 27 (54%) had three-line pattern. Serum progesterone level were significantly lower in patients who had positive BHCG than patients who had negative BHCG (p <0.001). Conclusion: Among women undergoing IVF, serum progesterone levels and also endometrial pattern (homogenous or three-line) was different. Serum progesterone level before the onset of treatment was related to the pregnancy outcome (positive or negative), as well as in women with lower progesterone levels in day before the start of progesterone suppositories, treatment with progesterone suppository could lead to better pregnancy outcomes following IVF, which is a novel and important finding.

Achieving maternal viral load suppression for elimination of mother-to-child transmission of HIV in South Africa.

To describe changes in maternal viral control over time in South African women living with HIV (WLHIV) using surveillance data from the National Health Laboratory Service's Corporate Data Warehouse (NHLS CDW). A retrospective cohort analysis of maternal viral load during pregnancy and up to 15 months postpartum was performed amongst WLHIV (15-49 years) within the public-health sector between 2016 and 2017. HIV and pregnancy-related test data were used to create a synthetic cohort of pregnant WLHIV from the NHLS CDW. Syphilis-screening, in association with ward type and/or postpregnancy cervical screening and/or birth HIV test and/or positive β-hCG, was used as a proxy for pregnancy. The syphilis-screening date marked the first antenatal care visit (fANC). Fractional polynomial models described viral load evolution from fANC up to 15 months postdelivery. Piecewise linear regression models determined factors associated with viral load decline. Among 178 319 pregnant WLHIV, 345 174 viral load tests were performed [median = 2 (IQR: 2-3) per woman]. At fANC, 85 545 (48%) women were antiretroviral therapy (ART) experienced; 88 877 (49.8%) were not and 3897 (2.2%) unknown. Proportions of viraemia (viral load ≥50 copies/ml) were 39 756 (53.6%) at first viral load performed during pregnancy, 14 780 (36.9%) at delivery and 24 328 (33.5%) postpartum. Maternal age at least 25 years, CD4+ cell count at least 500 cells/μl and viral load less than 50 copies/ml at baseline predicted sustained viral load suppression during follow-up. Despite high-ART coverage among pregnant women in South Africa, only 63% of WLHIV achieved viral load less than 50 copies/ml at delivery. Maternal viral load monitoring requires prioritization for maternal health and eMTCT.

Withholding antibiotics does not reduce clinical pregnancy outcomes of natural cycle frozen embryo transfers

To assess the impact of withholding doxycycline on the success rate of natural cycle frozen embryo transfers (NC-FET). Retrospective cohort study. Single academic institution. Women undergoing 250 NC-FET with euploid blastocysts performed by a single provider. One hundred and twenty-five NC-FET cycles performed after January 2019 without antibiotic administration compared with 125 NC-FET cycles before January 2019 with doxycycline administration. Primary outcome: live birth (LB) or ongoing pregnancy rate (OPR, defined as pregnancies ≥13 weeks); secondary outcomes included positive β-human chorionic gonadotropin (β-hCG) level and clinical pregnancy rate (CPR, defined as the presence of fetal cardiac activity on ultrasound). Each group of women comprised 125 NC-FET during the study period of March 2017 to March 2020. The women's mean age was 36.3 years and mean body mass index was 24 kg/m2. Between the two groups, the baseline characteristics were similar, including age, body mass index, race, smoking status, parity, endometrial thickness, Society of Assisted Reproductive Technology diagnosis, and number of prior failed transfers. Comparing NC-FET with doxycycline administration versus without, we found no statistically significant difference in LB-OPR (64% vs. 62.6%), positive β-hCG (72.8% vs. 74.0%), or CPR (68% vs. 65.9%). After controlling for all variables in a logistic regression, doxycycline still had no effect on LB-OPR. In this analysis of similar patients undergoing NC-FET by a single provider, withholding doxycycline does not reduce success rates. Given the risks of antibiotics, our findings support withholding their use in NC-FET.

Influence of EmbryoGlue® transfer medium on implantation of human embryos

Introduction: Thanks to ever-growing advances in medical science, couples who are in the in vitro fertilisation (IVF) now have more options than ever to encase their chances at a successful pregnancy. One of the options is the use of EmbryoGlue (EG), that creates a bridge between the embryo and the uterus and provides protection to the embryo itself during the transfer process. Aim of this study was to determine whether EG medium is of greater importance for embryo implantation than conventional medium in assisted reproductive technology and compare the rate of embryo implantation with EG and conventional medium in relation to the quality of the embryo, the age of the patients and tobacco smoking. Methods: The retrospective study included 50 patients who used EG medium in embryo transfer (ET) and 50 patients in the control group using conventional medium. All patients underwent ET after stimulation of the cycle according to a short protocol. ETs were done on Day 2, 3, or 5 in the blastocyst stage. Age and smoking status were recorded. Results: Out of a total of 100 patients, 42 patients had successful implantation and positive b-hCG 15 days after ET. In a control group 38 % had positive b-hCG and in the group of patients who used EG 46 %. A higher rate of embryo implantation success was observed on the second day of transfer in the group of patients using EG. In the EG group a significant increase in the embryo implantation rate was observed in patients older than 35. In tobacco smokers the implantation rate was higher if they used EG during ET. Conclusion: EG medium had a positive effect on the second day of ET, patients above the age of 35 and patients who were tobacco smokers.

Influence of clinical and paraclinical variables of the patient in the failure to achieve a pregnancy after embryotransfer: statistical analysis evaluation

We conducted this observational prospective study in order to establish to what extent do the clinical and paraclinical characteristics of the patient and the factors that determine infertility also negatively influence pregnancy rate (PR) per embryotransfer. We included 79 women who underwent 145 embryotransfers and we analyzed the positive β-hCG test result. We identified that the following parameters are not statistically significantly correlated to the failure rate: smoking (p=0.7230, OR=1.23), drug use (p=0.7850, OR=1.38), BMI (p=0.4210, OR=1.04), history of infertility, family illness (p=0.3212, OR=1.64), history of miscarriages (p=0.4438, OR=0.61) or abortions (p=0.9842, OR=0.99), previous ectopic pregnancy (p=0.6880, OR=1.30), dyspareunia (p=0.5400, OR=1.43), dysmenorrhea (p=0.4232, OR=0.65), endometriosis (p=0.1150, OR=2.43), impermeable fallopian tubes (p=0.1676, OR=2.11). AMH is not an independent risk factor for pregnancy failure either (p=0.1690, OR=0.79). Age and menarche are risk factors. Age predisposes to a 3.30 times higher failure rate to obtain a pregnancy (calculated cutoff: 34 years old; p=0.0210; OR=3.30). A patient who had menarche before 13 years old (calculated cutoff) has a four times higher risk of failure to obtain a biochemical pregnancy (p=0.0126, OR=3.91). As a conclusion, after reaching the embryo transfer point, the clinical and paraclinical characteristics of the patient are not independent negative factors on PR, except for patient’s age and menarche time.

Early and late pregnancy loss in women with polycystic ovary syndrome undergoing IVF/ICSI treatment: a retrospective cohort analysis of 21820 pregnancies.

To examine early and late pregnancy loss in women with and without polycystic ovary syndrome (PCOS) undergoing IVF/ICSI transfers. Retrospective cohort study. Reproductive medicine centre at a tertiary hospital. We studied women with a positive β-human chorionic gonadotropin (β-hCG) after in vitro fertilisation/intra-cytoplasmic sperm injection (IVF/ICSI) treatment from May 2014 to April 2019. Odds ratios (OR) for early (≤13weeks) and late (>13weeks) pregnancy loss were calculated among women with and without PCOS for plurality of the pregnancy with adjustment for confounding factors. Early pregnancy loss (EPL) and late pregnancy loss (LPL). From 21820 women identified with a positive β-hCG, 2357 (10.8%) women had PCOS, and 19463 (89.2%) women did not. EPL occurred in 16.6% (391) of women with PCOS versus 18.3% (3565) in women with non-PCOS (OR 0.89, 95% CI 0.79-0.99, P=0.04). After adjustment for age and other confounders, the rate of EPL was not statistically significantly associated with PCOS status (adjusted OR [aOR] 0.91, 95% CI 0.80-1.05). Women with PCOS demonstrated a higher rate of LPL (6.4% in PCOS versus 3.6% in non-PCOS, OR 1.81, 95% CI 1.48-2.21, P<0.001). In multivariable analysis, the potential impact of PCOS was less strong (aOR 1.38, 95% CI 0.96-1.98), with BMI and maternal comorbidities also associated with LPL (aOR 1.08, 95% CI 1.04-1.1 and aOR 2.07, 95% CI 1.43-3.00, respectively). Polycystic ovary syndrome was not independently associated with EPL. There was an increased risk of LPL but this difference was not statistically significant. Polycystic ovary syndrome women are at increased risk of late pregnancy loss, partly driven by elevated BMI and maternal comorbidities.

IS EARLY HCG PREDICTIVE OF PREGNANCY AFTER ESET IN BOTH FRESH AND FET CYCLES?

Most ART programs perform β-hCG measurement 9-12 days after embryo transfer(ET) to detect a pregnancy. A prior study using hyperglycosylated hCG in a small sample size showed that a single measurement 6 days after ET had 100% sensitivity and specificity in identifying biochemical and ongoing pregnancies. We sought to determine whether routine serum β-hCG measurement at 5-6 days after ET is predictive of ART outcome. This is important in patient counseling if we can stop P supplementation early in cases of negative tests, especially if taking painful IM P supplementation. Prospective single center. A total of 241 patients undergoing eSET (elective single embryo transfer) had their “early” serum β-hCG measured 5-6 days after ET, and the “official” serum β-hCG was done 9-10 days after ET. There were 91 fresh ET and 150 FET cycles. A test was positive if the β-hCG measurement was ≥ 3 IU/L. All tests were performed at a commercial laboratory with offices around the US (LabCorp). In the 91 fresh ET cases observed, 65 had positive and 26 had negative “early”β-hCG tests measured 5-6 days post ET. Of the 65 positive β-hCG tests, 10 (15.4%) were biochemical, 9 (13.8%) were pregnancy losses (SAB), and 46 (70.8%) were live births. Of the 26 negative tests, 24 (92.3%) were negative on days 9-10 and 2 (7.6%) were positive on days 9-10. Both positive results on day 9-10 ended with biochemical losses. In the 150 FETs observed, 81 had positive and 69 had negative “early” β-hCG. Of the 81 positive, 19 (23.5%) were biochemical pregnancies, 7 (8.6%) had SAB, and 55 (67.9%) were ongoing/live births. Of the 69 negative β-hCG tests measured 5-6 days post FET, 4 (5.7%) were then positive on day 9-10, 3 resulting in biochemical pregnancies and one live birth. The mean “early” β-hCG levels in the IVF group was 27.03 IU/L which was significantly higher than in the FET 14.09 IU/L (P<0.001). There were significant differences in early β-hCG results between ongoing/delivered and biochemical pregnancies in both fresh and FET groups (P<0.001), but not between ongoing/LB and SAB. However, by first β-hCG level on days 9-10 there were no differences in the mean β-hCG between the 2 groups (P=0.04). ROC for fresh ET showed a cut off value of 7 IU/L. The test can detect with 90% sensitivity a 96% specificity with 3.8% false positive (AUC=0.972). For FET it showed a cut off value of 3.7 IU/L. The test can detect with 89% sensitivity a specificity of 94% with 5.7% false positive (AUC=0.964) (Figure 1). Early serum β-hCG measured 5-6 days after ET in eSET cycles is very predictive of successful pregnancies. A negative test 5-6 days after ET is associated with a negative 9-10 day β-hCG test in both fresh and FET cycles. In the fresh group, an early negative β-hCG was 100% predictive of no live births, but in the FET group an early negative in the FET group led to a single live birth (99.33% predictive of no live births). FET cycles were associated with lower early β-hCG levels than fresh transfers but became similar to fresh cycles on the first day of actual pregnancy test. This information is of potential benefit in counseling women undergoing ART.

Primary hepatic pregnancy

Introduction. Hepatic pregnancy is an extremely rare form of ectopic pregnancy, and represents a difficult challenge for both diagnostics and treatment. Case outline. A 40-year-old gravida 0 para 0 patient in 6 + 0 gestational weeks was admitted to the hospital with lower abdominal pain, positive bHCG values, and presence of free intra-abdominal fluid. She had a history of infertility, and also a previous surgery due to pelvic endometriosis. Urgent open surgery was performed due to signs of hypovolemic shock. We discovered a rupture of the left ovarian corpus luteum cyst. Bleeding management was achieved with preservation of ovarian tissue. Patient recovered, bHCG levels continued to rise, and five days after surgery free intra-abdominal fluid reappeared with upper abdominal pain and tenderness. After transferring patient to abdominal surgery clinic, second surgery was performed, where we confirmed the presence of hepatic pregnancy. After this procedure, patient fully recovered. Conclusion. The method of choice for an ectopic pregnancy treatment is laparoscopic surgery, but when laparoscopy is not possible, the site of ectopic pregnancy could be difficult to diagnose. Prolonged time for making accurate diagnosis increases the risk of ectopic pregnancy complications.

Effect of autologous platelet-rich plasma on clinical outcome in patients with suboptimal endometrium in fresh ICSI/FET cycle − an interventional prospective study

Context: Endometrial receptivity (ER) is crucial for implantation rate and clinical pregnancy rate in ET-IVF. Endometrial receptivity is affected independently by endometrial thickness, vascularity and pattern. Aims: To evaluate the efficacy of autologous platelet-rich plasma in improving the endometrial parameters in patients with suboptimal endometrium in fresh ICSI/FET cycle. To evaluate pregnancy outcome in FET/ICSI cycles after intrauterine instillation of PRP. Settings and Design: Interventional prospective study conducted in tertiary infertility centre. Methods and Material: 30 patients with suboptimal endometrium undergoing IVF-ICSI/FET cycle with failed implantation/history of previous cycle cancellations/intrauterine adhesions on hysteroscopy were included. Patients with poor embryo quality, Bleeding dyscracias, Low platelet counts or active infections were excluded. All patients with any compromised endometrial parameter were offered intra-uterine PRP infusion. Statistical analysis used: Categorical data were presented as frequency and percentage; for comparison Chi square and McNemar tests were used wherever applicable for calculation of P-value. P-value < 0.05 was considered significant. Results: Endometrial thickness showed good response to PRP therapy and the mean increase in endometrial thickness was 1.33mm. PRP therapy significantly changed the endometrial pattern from Type A to Type B in more than half the patients (P-value = 0.001). PRP was instrumental in improving the sub-endometrial flow (22/30 patients, 73.3%) and uterine artery resistance (16/20, 80%), more so in subgroup of patients suffering from Intrauterine adhesions (P-value = 0.004 and 0.001 respectively). 43.3% (13/30) showed positive β-hCG. A clinical pregnancy rate of 30% (9/30) was seen. Conclusions: PRP has promising results in patients with suboptimal endometrium by increasing endometrial thickness, ameliorating pattern and improving vascularity with reduced cancellation rate.

Why Do Euploid Embryos Fail to Implant? The Role of CD138 and Chronic Endometritis

The objective of this prospective cohort study was to investigate the relationship between chronic endometritis (CE) and its treatment on pregnancy outcomes in patients undergoing frozen embryo transfers (FETs) from in vitro fertilization (IVF) with preimplantation genetic testing (PGT) who had previously failed ≥ 1 euploid FET. The diagnosis of CE was made using CD138 as a marker. This study occurred at a single, high volume academic based fertility center. 305 patients were included with a history of ≥ 1 failed euploid transfers. 59 patients underwent endometrial biopsies (EMB) prior to subsequent FET (Tested), 246 patients did not undergo EMB prior to subsequent transfer (Untested). Patients in the Tested group had an EMB prior to subsequent FET, whereas the patients in the Untested group did not have an EMB prior to next FET. Patients tested and found positive for CE were treated with antibiotics and underwent test-of-cure (TOC) EMBs prior to next FET to assess for adequate treatment. Patients without CE on EMB proceeded to next FET without antibiotic treatment. Main outcome measures included positive Beta-hCG (βhCG) on cycle day 28, implantation rate (IR), and subsequent ongoing pregnancy/live birth rates (OPR/LBR). Our results showed that 51% of patients (30/59) were diagnosed with CE and treated with antibiotics (Tested, CE treated); negative TOC biopsies were obtained prior to next FET. 49% of patients (29/59) tested negative for CE (Tested, No CE) and were not treated prior to next FET. Tested patients without CE (CE treated and No CE) had significantly higher incidences of positive βhCG, IR and OPR/LBR than patients who were not tested. Those who were biopsied and treated for CE had significantly higher OPR/LBR compared to patients who were biopsied and negative for CE (80% vs. 55%). We conclude that CE is common, with a prevalence of 51% in patients who have failed euploid FETs. Testing for CE may provide a benefit to patients, assuring higher incidences for positive βhCG, implantation, and subsequent ongoing/live births. CE is a treatable condition warranting investigation in patients with poor pregnancy outcomes.

Effect of vaginal estrogen cream on endometrial thickness in women under embryo transfer by applying long protocol method

Background and aims: Endometrial thickness (ET) is one of the main parameters in the success of assisted reproductive technology (ART) methods, which is influenced by sex steroids. This study investigated the effect of vaginal estrogen cream on ET in women undergoing embryo transfer. Methods: In this clinical trial, 100 infertile women candidates for embryo-fetal transfusion were enrolled in the study by a simple sampling method and then randomly divided into two treatment groups. For patients in group A, estradiol tablets were administered alone (control) and group B received the estradiol plus vaginal estrogen cream (intervention). The thickness of the endometrium was measured by ultrasound in both groups and recorded in the checklist. The rate of positive bHCG, pregnancy, and canceled cycles was evaluated in both groups as well. Finally, the data were analyzed using SPSS software. Results: Both groups were matched in terms of age (P=0.129). There was no significant difference between the groups regarding ET (P=0.651) and bHCG frequency (P=0.418) and the pregnancy rate was similar in two groups. Based on the results, the frequency of the canceled cycles was 32% and 50% in intervention and control groups (P=0.031).Eventually, no significant relationship was observed between pregnancy outcome (0.637) and the bHCG (0.553) test with ET. Conclusion: Overall, the administration of vaginal estrogen cream has no effect on ET and pregnancy rate in women under embryo transfer by applying the long protocol method in patients who referred to endometrium and endometriosis research center but it significantly reduces the eliminated cycles

2588. Acute Toxoplasmosis among Pregnant Arab Women in Northern Israel: to Screen or Not?

BackgroundThe seroprevalence of toxoplasmosis among Israeli Arabs is high. Yet, the regulation of the Israeli Ministry of Health suggests not screening pregnant women for toxoplasmosis. During 2017/8 we have seen a surge in cases of acute toxoplasmosis in pregnancy in Northern Israel. We aimed to explore this surge and compare the rates of acute toxoplasmosis in pregnancy in Northern Israel among Jews and Arabs.MethodsThe database of the lab of Meuhedet HMO (Northern Israel only) was retrospectively screened for all tests for Toxoplasma serology during 2013–2017. We focused on women of childbearing age and compared rates of seropositivity in Jews and Arabs. IgG and IgM were carried out using Abbott Architect, and IgG avidity by Vidas, BioMerieux. Birth rates were retrieved from the central computer of Meuhedet HMO.Results: In 2017, Northern Israel had 1,397,833 citizens of whom 53% were Arabs. Of this population, 13% were insured by Meuhedet HMO, and of these 60% were Arabs (Muslims or Christians). During the 5-year period 16,044 Toxoplasma serology tests have been requested (both sexes), of which 26% returned IgG positive. 88% of the positive ones were of Arab citizens (P < 0.0001). Excluding duplicates, we found 118 women of childbearing age with a positive IgM test (2.8%). Of the latter, 37 had a low/medium avidity test (31.4%). 112 of the women were Arabs, while only 6 were Jews (P < 0.0001). Two-thirds of the women had a positive βHCG test at the same time. During this 5-year period there were 23,074 live births in this HMO (11,512 Arab newborns). Thus, had all these women delivered an infected newborn, the rate of congenital toxoplasmosis in the Arab population (97.2/10,000) was 19-fold higher than among the Jewish (5.2/10,000; P < 0.00001). Interview of 35 acute cases during 2017/8 revealed that most of the women had consumed raw meat called “Kibbe Niyye”—a popular dish unique to Northern Israeli Arabs (Galilee) and served on festive occasions.ConclusionWe found that Northern Israeli Arab women are at a high risk to contract toxoplasmosis during pregnancy due to consumption of traditional raw meat. This finding calls for awareness among women as well as doctors. We believe that the regulation not to screen pregnant women in the Arab sector should be reevaluated.Disclosures All authors: No reported disclosures.

1253 A Descriptive Analysis of Anomalous Ectopic Pregnancies

Study Objective The majority of ectopic pregnancies implant in the fallopian tube; however, 10% implant in non-tubal locations including the abdominal cavity, cervix, ovary, interstitium of the fallopian tube, broad ligament, uterine cornua, and cesarean section scar. The objective of this study is to describe the characteristics and history of patients presenting with anomalous ectopics encountered at North Shore University Hospital/Long Island Jewish (NSUH/LIJ) from 2016 to 2018. Design A descriptive analysis of the anomalous ectopics encountered at NSUH/LIJ from 2016 to 2018. Setting Patients presented to the emergency room and were treated medically or in an operating room setting at NSUH/LIJ. Patients or Participants 55 women of reproductive age presented to NSUH/LIJ with pelvic pain and a positive bHCG and were determined to have an ectopic pregnancy in a non-tubal location. Interventions Patients with heterotopic, ovarian, cervical, cesarean section scar and interstitial ectopics were primarily treated via minimally invasive laparoscopic excision. Those with cesarean section scar and cervical ectopics were managed with methotrexate and intracervical balloons. Measurements and Main Results The incidence of patients with anomalous ectopics was 13.6%. The average age at diagnosis was 35. 74.5% in this cohort reported to be never smokers. 74.5% reported having previous abdomino-pelvic surgery. 74.5% did not use ART prior to their presenting diagnosis. The breakdown of ectopics was- Cesarean scar (27.3%), Cornual (23.6%), Interstitial (20.0%), Cervical (16.4%), Heterotopic (5.5%), Abdominal (3.6%), and Ovarian (3.6%). Conclusion Anomalous ectopic pregnancies in the NSUH/LIJ population of patients are 3.6% more prevalent than that reported by current data. Although these patients did not report use of ART in association with the anomalous pregnancy, many of these patients reported having previous abdominopelvic surgeries. C-section scar ectopics were the most prevalent, which may be secondary to the higher rate of c-sections in the last decade.

Outcomes of a simplified mosaic ranking system

Investigating outcomes of transferring mosaic embryos according to a simplified classification system that replaced our more complex 1-9 ranking system. Following previous implementation of a comprehensive mosaicism classification system, a review of our mosaic embryo outcome data, together with that of recent literature (Spinella et al 2018, and Munne et al 2017) was conducted. The goal was to introduce a more simplified classification system – using an A-D grading – which ranks mosaic embryos for clinical use (as per table below). The study included 158 single transfers of embryos (between April 2016 to February 2019) which exhibited a mosaic shift (ranging from 20-79%) using NGS technology. TF-A = NAD (no abnormality detected) – first choice for transfer TF-B = Noisy result/low level mosaicism <=40% – second choice TF-C: MOSAIC (significant mosaicism detected >40-< 80%) -third choice, further stratified by: C1: -segmental -low risk chromosomes C2: -high risk chromosomes TF-D: ABN (abnormal) – not available for transfer Mosaic embryos were separated into the above categories dependent on the percentage of mosaicism present in the sample and the chromosome involved, with only levels over 40% being reportable findings. This study retrospectively compared the positive bHCG and fetal heart (FH) outcomes for the TF-A, B and C groups. We also analyzed outcomes for whole chromosome mosaics compared to segmental mosaic findings. We found that overall, TF-A group had the highest positive bHCG rates (62.9%) and FH rates (53.7%) followed by TF-B bHCG (57.6%) and FH rates (47.6%). TF-C had lower positive bHCG rates outcomes (44%) and FH rates (36%). Analysing TF-C (40-80% mosaics) in more detail we found that segmentals had higher bHCG and FH rates (69.2% and 61.5%) compared to whole chromosome mosaics (20% and 10%). Furthermore, irrespective of the mosaic percentage, all single segmentals (in the 20-80% range) had clearly better outcomes than multiple segmentals (bHCG; 63.3% vs 44.4% and FH; 48.3% vs 33.3%). In comparison low level segmental mosaics (<=40%) had higher bHCG (58.9%) and FH (42.9%) rates compared to low level whole chromosome mosaics (44.8%) and (36.2%). Overall the positive bHCG and fetal heart outcomes support the simplified classification system and the concept of preferentially transferring low level before high level whole chromosome mosaics in the absence of NAD embryos. Single segmental mosaic embryos have improved clinical outcomes compared to whole chromosome mosaic embryos and should be considered for preferential transfer ahead of other types of mosaic findings. Whole chromosome mosaics should be considered last choice.