Live Birth Rate In Women Research Articles

Aromatase inhibitors (letrozole) for ovulation induction in infertile women with polycystic ovary syndrome.

Aromatase inhibitors (letrozole) for ovulation induction in infertile women with polycystic ovary syndrome.

GnRH-agonist pretreatment in hormone replacement therapy improves pregnancy outcomes in women with male-factor infertility.

ObjectiveThis study aimed to examine the efficacy of HRT with gonadotropin-releasing hormone agonist (GnRH-a) pre-treatment in women with male-factor infertility who underwent a frozen embryo transfer (FET) programme.DesignBetween January 2016 and October 2020, 2733 women with male-factor infertility who underwent the HRT protocol as the endometrial preparation method were enrolled at two Reproductive Medicine Centres. Patients were divided into two groups based on whether they had GnRH-a pre-treatment before HRTs: the GnRHa-HRT group and the HRT group. The inverse probability of treatment weighting (IPTW) method was conducted to balance patient baseline characteristics between treatment cohorts to reduce selection bias. The live birth rate was considered regarded as the primary pregnancy outcome.ResultsMultivariate logistic regression adjusted for confounding factors, the GnRHa-HRT group showed a notably higher rate of live birth (OR 2.154, 95% CI 1.636~2.835, P<0.001) when compared to the HRT group. Additionally, the rate of miscarriage was significantly lower in the GnRHa-HRT group. The GnRHa-HRT group had significantly higher rates of biochemical pregnancy, clinical pregnancy, multiple pregnancy, and term birth.ConclusionThe endometrial preparation protocol of HRT with GnRH-a pre-treatment could obviously increase the live birth rate for women with male-factor infertility undergoing the FET programme.

Comparison of two gonadotropin-releasing hormone agonist suppression protocols for in vitro fertilization in young patients with low body mass index.

To evaluate two different gonadotropin-releasing (pituitary downregulating) hormones used in in vitro fertilization (IVF) on the live birth rate in young patients with low body mass index (BMI) undergoing their first IVF cycle. In a retrospective study in a single public medical center, 555 long gonadotropin-releasing hormone agonist (GnRH-a) protocols were compared with 431 prolonged GnRH-a protocols between 2016 and 2018. All analyses were performed using the SPSS version 22.0. The primary measured outcome was live birth rate. Compared with the long protocol, the prolonged protocol required more doses of gonadotropin and a longer duration of ovarian stimulation. Lower levels of serum luteinizing hormone and serum estrogen were detected on the day of chorionic gonadotropin administration, and a lower fertilization rate was found in the prolonged protocol. Although more oocytes were retrieved and more frozen embryos were recorded in the prolonged protocol, the live birth rate per fresh cycle was comparable between the two protocols (P= 0.057). The incidence of ovarian hyperstimulation syndrome was higher in the prolonged protocol group. In the subgroup of women with antral follicle count (AFC) of 12 or less, there was no difference in the live birth rate between the two protocols (P= 0.688). However, for women with AFC > greater than 12, the prolonged protocol was still a positive predictor of live birth rate. The odds ratio was 1.73 (95% confidence interval 1.04-2.89). The prolonged protocol might not increase the live birth rate in women with low BMI who are undergoing their first IVF cycle. However, for women with AFC greater than 12, a prolonged protocol could be a good choice to improve the live birth rate.

Effect of Dual Trigger In Vitro Fertilization and Intracytoplasmic Sperm Injection During the Gonadotropin-releasing Hormone-Antagonist Cycle on Final Oocyte Maturation and Cumulative Live Birth Rate in Women with Diminished Ovarian Reserve.

It is well known that a dual trigger treatment can improve clinical outcomes of in vitro fertilization (IVF) in high or normal ovarian responders. However, it is not clear whether dual triggering also benefits patients with diminished ovarian reserve (DOR). The aim of this study was to investigate whether a dual trigger treatment of gonadotropin-releasing hormone (GnRH) agonist combined with human chorionic gonadotropin (hCG) for final follicular maturation improves the cumulative live birth rate (CLBR) during the GnRH-antagonist cycle in patients with DOR. This retrospective study included patients with DOR who received a GnRH-antagonist protocol during IVF and intracytoplasmic sperm injection (IVF-ICSI) cycles at Peking University People's Hospital from January 1, 2017 through December 31, 2017. Oocyte maturation was triggered by GnRH combined with hCG (n=110) or hCG alone (n=71). Embryos were transferred on the third day after oocyte retrieval or during a subsequent freeze-thaw cycle. Patients were followed up for 3 years. The dual trigger treatment did not affect CLBR, which is an overall determinant of the success rate of assisted reproductive technology (ART). Women in the dual trigger group had significantly higher rates of fertilization than those in the hCG group (90.1% vs. 83.9%, P=0.040). Dual trigger with GnRH agonist and hCG did not improve CLBR in patients with DOR, but did slightly improve fertilization rate, oocyte count, and embryo quality.

Pregnancy outcomes following in vitro fertilization treatment in women with previous recurrent ectopic pregnancy.

ObjectivesThe aim of this study was to investigate the impact of a history of recurrent ectopic pregnancy (EP) on pregnancy outcomes of subsequent in vitro fertilization (IVF) treatment.MethodsA retrospective cohort study involving 457 women with a history of recurrent EP (REP group), 912 women with a history of single EP (SEP group), and 1169 women with a history of intrauterine pregnancy (IUP group) as the control group, was conducted. IVF outcomes were compared for each cohort.ResultsThe incidence of EP in the REP group after IVF treatment was significantly lower than those in the SEP group (2.4% vs. 6.8%, P = 0.011), and similar to those in the IUP group (2.4% vs. 2.1%, P = 0.830). No significant differences were observed in the clinical pregnancy rate, miscarriage rate, and live birth rate among the three groups. There was no statistically significant difference in the recurrent EP rate between the salpingectomy and salpingostomy treatments. Adjusting for maternal and treatment factors did not influence live birth rates for women with previous REP compared with women with previous SEP and those with IUP. The odds of EP were 82.2% lower (OR 0.178, 95% CI 0.042–0.762; P = 0.020) in women who had blastocyst transfer compared with cleavage embryo transfer in the SEP group. The odds of EP were over six times (OR 6.260, 95% CI 1.255–31.220; P = 0.025) in women who underwent double embryo transfer as opposed to single embryo transfer in the IUP group.ConclusionOur results indicate that women with previous recurrent EP have a lower risk of EP after IVF in comparison with women with previous single EP. Previous EP has no significant adverse effect on the main IVF outcomes. The salpingostomy and salpingectomy treatments of EP do not significantly affect the incidence of recurrent EP after IVF.

Association between duration of controlled ovarian stimulation and live birth rate in women undergoing In Vitro Fertilization: a SART CORS analysis

Background: In-Vitro Fertilization (IVF) treatment involves synchronization of multiple time-sensitive events, most of which are rate-limiting too. Controlled ovarian stimulation (COS) is one such event. The reproductive outcomes based on the duration of COS (d-COS) in a fresh, IVF embryo transfer (ET) are not well established and therefore, remains largely uncertain. Objective: To evaluate the association between d-COS and live birth rate (LBR) in women undergoing a fresh IVF-ET using autologous oocytes. Methods: A retrospective cohort study was conducted using a US nationwide IVF register – SARTCORS (Society for Assisted Reproductive Technology Clinic Outcomes Reporting System). From a total of 93,889 cycles, we included 56,666 fresh, autologous, IVF - ET treatment cycles from January 2014 through December 2015, with follow-up until October 2016. Adjusted odds and risk ratio with 95% confidence intervals were estimated while controlling for multiple demographic factors and other potential confounders. Variables and outcomes: The primary exposure variable was d-COS defined as the difference in days between gonadotrophin administration and oocyte retrieval. The primary outcome measure was live birth following a fresh IVF-ET. Secondary outcome measures included biochemical pregnancy rate, miscarriage rate, implantation rate and clinical pregnancy rate. Results: A total of 56,666 treatment cycles (mean [SD] age of 33.9 [4.47], BMI of 26.1 [6.02], AMH value of 2.19 [3.37]), and a baseline FSH value of 7.62 [3.49]) underwent a fresh IVF-ET. The LBR after a combined analysis for all ages and all protocols was 44.2 % (n = 25043). In the combined analysis, there was a statistically significant decrease in the live birth rate with LBR with d-COS beyond 10 days. The adjusted OR (95% CI) of LBR for a woman who had 11, 12, 13 and ≥14 days of COS, compared to optimal duration of 10 days was 0.97 (0.87-0.99), 0.94 (0.8-1), 0.83 (0.77-0.89) and 0.73 (0.68-0.79) respectively. The AOR (95% CI) of miscarriage rates for a woman who had 11, 12, 13 and ≥14 days of COS, compared to referent was 1.12 (1-1.26), 0.99 (0.87-1.12), 1.03 (0.90 -1.17) and 1.04 (0.90 - 1.2) respectively. With increasing d-COS, the implantation rate (IR) and clinical pregnancy rate (CPR) also showed a decreasing trend, as with other reproductive outcomes. The RR (95% CI) for implantation rate in a woman who had 11, 12, 13 and ≥14 days of COS, compared to referent was 0.97 (0.93-1), 0.97 (0.93-1.01), 0.91 (0.87-0.95) and 0.86 (0.82-0.9). The adjusted OR (95% CI) of CPR for a woman who had 11, 12, 13 and ≥14 days of COS, compared to referent was 0.95 (0.89-1.01), 0.93 (0.87-0.99), 0.8 (0.75-0.86) and 0.7 (0.65-0.75) respectively. Conclusions and Relevance: In this nationwide cohort study of women undergoing fresh IVF-ET using autologous oocytes, controlled ovarian stimulation lasting approximately 10-days was associated with an optimal live birth rate.

P-581 Live birth rates in women under 38 years old with AMH level &amp;lt; 1.2 ng/ml in in-vitro fertilization/intracytoplasmic sperm injection: arguments for care

Abstract Study question To evaluate the clinical pregnancy and live birth rates in the first IVF/ICSI cycle in women under 38 years old with AMH level &amp;lt; 1.2 ng/ml. Summary answer Our findings argue to propose IVF for those patients. What is known already Many studies failed to show a predictive impact of AMH levels on the chances of pregnancy, however acceptable pregnancy rates for young women with low AMH levels were observed in IVF/ICSI. The definition of early ovarian failure is based on two classifications, Bologna and Poseidon, where an AMH level of 1.2 ng/ml appears to be the threshold for determining ovarian failure. According to La Marca's curve, this level of 1.2 ng/ml corresponds to an ovarian reserve of a 38 year-old woman. Study design, size, duration The primary objective of this study was to compare the live birth rates between these three groups of women. The secondary objective was to compare the rate of positive βhCG level, clinical pregnancy rate and live birth rate in women under 38 years of age during the 1st cycle of IVF+/-ICSI, regardless of whether the AMH is &amp;lt; 1.2 ng/ml or ≥ 1.2 ng/ml. Participants/materials, setting, methods We analyzed the first cycle of IVF/ICSI in women under 38 years old with AMH level &amp;lt; 1.2 ng/ml under long GnRH agonist or GnRH antagonist protocols. We classified the women into three groups: group A: AMH &amp;lt; 0.4 ng/ml; group B: AMH: 0.4 to 0.8 ng/ml; group C: AMH &amp;gt; 0.8 ng/ml. Main results and the role of chance Between January 2017 and September 2020, we retained 227 cycles for analysis (group A: 50 cycles, B: 85 cycles and C: 92 cycles). No significant difference was found between the three groups for clinical pregnancy and live birth rates, either per stimulation cycle, oocyte puncture or embryo transfer. Thus, the birth rates per embryo transfer are 23.5% in group A, 25.4% in group B and 28.1% in group C. When we compared the two groups of women under 38 years of age during the 1st cycle of IVF+/-ICSI, according to AMH levels &amp;lt; 1.2 ng/ml (n: 227) or ≥ 1.2 ng/ml (n: 325), the only significant difference was the positive βhCG level rate per oocyte puncture (p &amp;lt; 0.01). Biochemical pregnancy rates were significantly different in women with AMH &amp;lt; 1.2 ng/ml (40.8%) compared to those with AMH ≥ 1.2 ng/ml (16.6%; p &amp;lt; 0.01), but the rate of first trimester miscarriage was identical in both groups (14.6% and 6.1% respectively). Limitations, reasons for caution Our retrospective study and the small sample size limited the level of scientific proof. The woman and male ages were significantly different between the AMH groups, but these data lead to reduce the impact of low AMHs on pregnancy rates. Wider implications of the findings The young age of the women (&amp;lt; 38 y.o) reassures about the oocyte quality, but a low level of AMH may raise concerns about a lower quantitative oocyte yield, leading to accelerated management of the couple in IVF/ICSI. Trial registration number B2020CE.43

Association of ABO blood groups and ART outcomes among subfertile South Asian women: a retrospective cohort study

BackgroundBlood groups are expressed on the surface of the red cells, and their association with the ovarian reserve and pregnancy outcomes has been an area of interest. The aim of the current study is to study the association of blood groups with live birth rates among South Asian women undergoing assisted reproductive technology treatment. It is a retrospective cohort analysis of women undergoing assisted reproductive technology (ART) at Christian Medical College and Hospital, India, between January 2007 and June 2017. All women ≤ 40 years undergoing the first ART cycle with fresh embryo transfer were included and stratified into four groups (A, B, AB, and O) based on the blood group type. The ART outcomes were analyzed among the groups.ResultsA total of 2524 women underwent fresh embryo transfer cycles during the study period, among whom 2079 women were analyzed. There was no statistically significant difference in the live birth rates for women with blood group B (odds ratio, OR 0.96, confidence interval, CI, 95% 0.74–1.24), blood group AB (OR 0.89, 95% CI 0.58–1.35), and blood group O (OR 0.87, 95% CI 0.68–1.12) with blood group A as the reference. After adjusting for important confounders, there was no statistically significant difference in the live birth rates for women with blood group B, AB, and O in comparison with blood group A.ConclusionThe current study showed no association of blood groups with the ART treatment outcomes in South Asian women.

P-427 Pregnancy outcomes following recurrent first-trimester miscarriage: a retrospective cohort study

Abstract Study question What are the subsequent pregnancy outcomes (livebirths, miscarriages or other adverse pregnancy outcomes) in a cohort of women with recurrent miscarriage (RM)? Summary answer The overall live birth rate in women with RM was 62% (466/748), falling to 44% in women aged &amp;gt;40 and 54% in women with infertility. What is known already RM affects approximately 1% of women of reproductive age. RM is recognized as a prognostic indicator for subsequent pregnancies and adverse pregnancy outcomes including ante-partum hemorrhage, diabetes, preterm birth, small for gestational age and perinatal death. While RM has known associations with advanced maternal age, obesity, diabetes, thyroid dysfunction and endometriosis, approximately 50% of women/couples will be left without an explanation for their pregnancy loss, even after completing investigations. Study design, size, duration A retrospective cohort study was undertaken to identify subsequent pregnancy outcomes in women with RM, where RM referral criteria are 3 consecutive first-trimester miscarriages. Women attending the pregnancy loss clinic at a tertiary university hospital in the Republic of Ireland over a 12-year period (2008 - 2020) with a confirmed diagnosis of primary or secondary first-trimester RM were eligible for inclusion. In total, 923 charts were identified for review against the eligibility criteria. Participants/materials, setting, methods Women with non-consecutive first trimester miscarriages or ectopic pregnancy were excluded. Epidemiological and clinical information was gathered from paper and electronic medical records. Data were analysed descriptively using SPSS (Version 27). Main results and the role of chance Of 748 women identified, 332(44%) had primary RM, 416(56%) had secondary RM. The median age was 36(range 19-47) years with 12% aged under 29 and 64% of women aged ≥35. 142(19%) had a history of infertility with 43(5.7%) attending for ART. 12% of women had anti-nuclear antibodies(89/742), 8% had abnormal thyroid function tests(60/742), 4.7% were heterozygous carriers of the Factor V Leiden gene mutation(35/737), 1.5% had positive anti-cardiolipin antibodies(11/733), 2% were carriers of a Prothrombin gene mutation(7/343) and 1% had elevated HbA1c levels(7/742). Fetal karyotype was recorded in 141 pregnancies, with 111 abnormal results(78%;111/141). Trisomy(T) 16 was most common(17/111; 15%) followed by T21 and T22(n = 14; 13%). Parental karyotyping of 697 sets of parents identified 28 balanced translocations(4%; 28/697). Prescribed pharmacological treatments included high dose folic acid(75%; n = 548/728), aspirin(96%; 696/726), progesterone (52%; 389/728), tinzaparin(24%; 175/727), prednisolone(4%; 28/726), metformin(2%; 12/727) and hydroxychloroquine(1%; 7/727). 573 women had a subsequent pregnancy (76.6%); 359(62%; 359/573) had a live birth, 190 had a miscarriage(33%) and 18(3%) had an adverse pregnancy outcome such as ectopic pregnancy, stillbirth or second-trimester miscarriage. Including successive pregnancies over the study period, the overall live birth rate was 62%(466/748), falling to 44% in women aged &amp;gt;40 and 54% in women with infertility. Limitations, reasons for caution This work covers a 12-year period, and while the RM clinic staffing is largely unchanged, some changes in management of RM patients has occurred in this time, reflecting up-to-date evidence and greater public awareness. Furthermore, the adoption of an electronic health chart in 2017 may have affected data availability. Wider implications of the findings Our findings confirm RM occurs more frequently in women aged &amp;gt;35. Aneuploidy remains a leading cause of miscarriage. Age is a prognostic indicator for livebirth after RM. These findings will facilitate counselling in this cohort. The substantial rates of prescribed medications and infertility in women with RM merit further exploration. Trial registration number N/A

P-729 The cumulative clinical pregnancy and live birth rates of IVF in women treated for genital tuberculosis are similar to those in other infertility etiologies

Abstract Study question Is cumulative clinical pregnancy rate (CPR) and live birth rate (LBR) in infertile patients with treated genital tuberculosis similar to other infertility etiologies undergoing IVF? Summary answer There is no significant difference in cumulative CPR and LBR in women adequately treated for genital tuberculosis undergoing IVF compared to other etiology of infertility. What is known already Female genital tuberculosis (FGTB) is an important cause of infertility in high tuberculosis prevalent countries. The uterine endometrial environment is an important cradle for embryo development. Once violated with infection, the damage to the endometrial blood flow and uterine cavity morphology is likely to be irreversible leading to infertility even after cure with anti-tuberculosis therapy (ATT). Adequate treatment of FGTB involves medical therapy with ATT and surgical treatment of hydrosalpinges and endometrial adhesions. The cumulative CPR and LBR are reported to be lower in the treated endometrial tuberculosis than in non-tuberculosis infertile patients undergoing IVF. Study design, size, duration This is a retrospective analysis of women who underwent IVF with self-oocytes over a period of 4 years from 2015 to 2018. All patients were divided into two groups as: Group-1: All women treated with ATT for FGTB before IVF with all presentations including women who underwent surgery for hydrosalpinges or intrauterine synechiae except with severe intrauterine adhesions and unfit for embryo transfer (ET) Group-2: Patients undergoing IVF other infertility etiologies. Participants/materials, setting, methods Women undergoing ovum pickup along with subsequent fresh and frozen embryo transfer attempts until attained a live birth or all the embryos were used. Exclusion criteria: Main results and the role of chance A total of 948 women underwent OPU during the study period. 171 were excluded from analysis for following reasons: Total of 775 women were included for analysis and results are summarized as: The mean number of embryos per OPU was 7.04 in Group-1 while 6.97 in Group-2. A total of 195 ET procedures were done in Group-1 while 1035 in Group-2. The mean number of ET procedures required for one clinical pregnancy in Group-1 was 3.15 and 2.81 in Group-2.The mean number of ET procedures required for one live birth in Group-1 was 3.42 and 3.02 in Group-2. CPR per ET procedure in Group-I was 31.79% while 35.55% in Group-2. All these differences were statistically insignificant. Limitations, reasons for caution The FGTB has a wide spectrum of presentation from a very early sub-clinical disease to an advanced stage with pelvic organ damage. The prognosis of IVF varies with the extent of disease. This study analyzed overall result while sub categories of FGTB were not analyzed. Wider implications of the findings Infertility after ATT treated FGTB has good IVF outcome. IVF outcome in these patients need to be studied based upon the extent of damage. We recommend undertaking an early IVF with good hope of live birth in ATT treated FGTB. Trial registration number Not applicable

P-540 Is there a necessity to process preimplantation genetic aneuploidy testing (PGT-A) of embryos in all patients undergoing Assisted Reproductive Technology (ART) programs?

Abstract Study question Should each embryo undergo preimplantation genetic testing for aneuploidy (PGT-A), or a personalized approach following indications such as age should be applied? Summary answer PGT-A does not increase clinical pregnancy and live birth rates in women under 35, however results are significantly improved for female patients over 35 years. What is known already PGT is a powerful tool in standard IVF practice however, despite all the benefits of the technology, it remains one of the most controversial topics that continue to generate interest, discussion, and debate in the field of reproductive medicine. Proponents believe that the potential of PGT-A allows effectively selecting a euploid embryo based on its genetic status and achieving a result in a short time regardless of the patient's age. Opponents consider that PGT-A cannot reflect the chromosomal status of the entire embryo with 100% accuracy, and embryo manipulation is inherently invasive and traumatic, which may reduce the life-birth potential. Study design, size, duration The retrospective single-center study included 2164 ART cycles performed from 2017 to 2020 at the Institute of Reproductive Medicine, Almaty, Kazakhstan. Clinical pregnancy rates (CPR), live birth rates (LBR), and pregnancy losses were analyzed. Results of frozen embryo transfer (FET) cycles with PGT-A as Group A (n = 637), FET without PGT-A as Group B (n = 705) and fresh cycle transfer as Group C (n = 822) have been compared. Moreover, selection were categorized by female age: ≤35 and &amp;gt;35. Participants/materials, setting, methods In the “fresh” IVF cycle (Group C), day 5 blastocysts of excellent/good quality according to the Gardner classification were selected for transfer. Trophectoderm (TE) biopsy of about 5-10 cells was performed on day 5/6 followed by vitrification (Kitazato). PGT-A was processed by comparative genomic hybridization (aCGH) on the Agilent platform. The transfer of thawed embryos of Group A (with PGT-A) and Group B (without PGT-A) was conducted into the uterine cavity under ultrasound control. Main results and the role of chance A total of 2318 blastocysts have been analyzed for the study. The proportion of euploid/aneuploid embryos in females under 35 years was 60.5/39.5%, respectively. In the category of over 35, this ratio was inverse - 41.9/58.1%. The results of the study haven't revealed statistical differences in age category under 35 years in CPR between Groups A, B, and C and amounted to 58.9% (227/385), 58.7% (637/1084), and 58.9% (482/936), respectively. However, in the category of women over 35 CPR was significantly higher (p &amp;lt; 0.001) in Group A - 53.2% (134/252) compared with Groups B - 40.9% (167/408) and C - 39.0% (185/474). Early pregnancy losses in patients under 35 in Group B were remarkably higher compared to Group A and composed to 12.2% (16/227) vs 7.1% (78/637), respectively (p &amp;lt; 0.05). A similar trend was traced in these groups in females over 35 -14.4% (24/167) vs 8.9% (12/134). The percentage of LBR in women over 35 years was significantly higher (p &amp;lt; 0.001) in Group A - 48.4%, compared to Groups B and C (35 and 34.2%). We did not find a notable difference between the two groups in women aged under 35. Relationships between variables were assessed by Student’s T-test. Limitations, reasons for caution The current study is limited due to the results of mosaic embryo transfers were excluded. Wider implications of the findings Although using PGT-A is growing each year, a significant increase in the rate of CPR and LBR was noted only in women over 35 years of age. However, concerning safety, in patients undergoing PGT-A, the risk of having a child with chromosomal diseases is significantly reduced. Trial registration number NA

O-021 Levothyroxine in Euthyroid Thyroid Peroxidase Antibody positive Women with Recurrent Pregnancy Loss: a multicentre, randomised, double-blind trial (T4LIFE trial)

Abstract Study question Does levothyroxine treatment increase live birth rates in thyroid peroxidase antibodies (TPO-Ab) positive women with recurrent pregnancy loss (RPL) and normal thyroid function? Summary answer Levothyroxine treatment did not result in higher live birth rates in women with RPL positive for TPO-Ab and a normal thyroid function, compared to placebo. What is known already Women positive for TPO-Ab have a higher risk of RPL. Levothyroxine supplementation has been proposed to reduce the risk of pregnancy complications. Evidence is limited whether levothyroxine treatment improves pregnancy outcomes in TPO-Ab positive women with RPL. Study design, size, duration We conducted an international double-blind trial. Between January 2013 and September 2019, we randomly assigned 187 women to receive levothyroxine (94 women) or placebo (93 women). Before conception, women were randomly assigned in a 1:1 ratio to levothyroxine or placebo orally once daily. The daily dose of levothyroxine was based on preconception TSH concentration and ranged from 0.5 to 1.0 µg/kg bodyweight. Levothyroxine or placebo was continued until the end of pregnancy. Participants/materials, setting, methods Patients with two or more pregnancy losses underwent diagnostic testing for RPL. Women with a normal TSH level and positive for TPO-Ab were eligible for the study. Antiphospholipid syndrome was an exclusion criterion. The primary outcome was live birth, defined as the birth of a living child beyond 24 weeks of gestation. Secondary outcomes included ongoing pregnancy, pregnancy loss, preterm delivery, adverse events and time to conception leading to live birth. Main results and the role of chance Live birth occurred in 47 women (50%) in the levothyroxine group and in 45 women (48%) in the placebo group (risk ratio, 1.03; 95% confidence interval [CI], 0.77 to 1.38; absolute risk difference 1.6%; 95% CI, -12.7% to 15.9%). There were no significant differences in any secondary outcomes. In both groups seven adverse events were reported, none of them directly related to the study procedure. Limitations, reasons for caution The slow recruitment forced us to stop the trial prematurely. With this sample size we are not able to fully account for dropouts and the estimates have wide 95% confidence intervals. Detection of a difference of 5% in live birth rate would have required inclusion of more than 3000 women. Wider implications of the findings Routine use of levothyroxine in women with RPL and normal thyroid function positive for TPO-Ab is not recommended. Our results are in line with previous trials in TPO-Ab positive women with a history of infertility or pregnancy loss or undergoing in vitro fertilization. Trial registration number Netherlands Trial Register (NTR3364).

Low molecular weight heparin and pregnancy outcomes in women with inherited thrombophilia: A systematic review and meta-analysis.

To determine whether the use of low molecular weight heparin (LMWH) improves the pregnancy outcomes in women with inherited thrombophilia by conducting a meta-analysis of randomized controlled trials and observational studies. A systematic literature search of several databases was conducted through September 19, 2020 to identify relevant studies. The outcomes of interest included live birth and adverse pregnancy outcomes (APOs). The overall risk estimates were pooled using random-effects meta-analysis. Ten randomized controlled trials and 12 cohort studies were included. In the meta-analyses of randomized controlled trials, the effectiveness of LMWH-treatment was found to be statistically significant in decreasing the risk of APOs (risk ratio [RR]=0.76; 95% confidence interval [CI]: 0.61-0.95; p=0.020), rather than in increasing the rate of live birth (RR=1.12; 95% CI: 0.93-1.34; p=0.230). In the meta-analyses of cohort studies, results showed that the use of LMWH was associated with a significantly higher proportion of live birth (RR=1.86; 95% CI: 1.09-3.19; p=0.020) as well as a significantly lower ratio of APOs (RR=0.46; 95% CI: 0.31-0.69; p < 0.001) in women with inherited thrombophilia. The use of LMWH may have a potentially beneficial effect on reducing the risk of APOs and even increasing the live birth rate in women with inherited thrombophilia. Further well-designed clinical trials with large samples are needed to address the role of LMWH in improving pregnancy outcomes among pregnant women with inherited thrombophilia.

Assessment of in vitro fertilization outcomes after hysteroscopic isthmoplasty in recurrent implantation failure.

The aim of this study was to assess the in vitro fertilization (IVF) treatments outcomes of women with recurrent implantation failure (RIF) after hysteroscopic isthmoplasty for isthmocele. This retrospective, observational study included 61 patients with RIF and isthmocele who presented to IVF Unit of Hüma Obstetrics and Gynecology Hospital between January, 2018 and December, 2020. Thirty-one patient who underwent hysteroscopic isthmoplasty-before IVF procedure-were included. Remaining 30 patients underwent IVF without hysteroscopic isthmoplasty were included as controls. The fertility outcome were compared between groups. After 3months, spontaneous pregnancy was achieved in 18.4% (7/38) of patients with isthmocele who underwent hysteroscopic isthmoplasty. In the isthmoplasty group, implantation rate, clinical pregnancy rate, biochemical pregnancy rate, and the miscarriage rate were 41.9% (13/31), 35.5% (11/31), 6.5% (2/31), and 9.7% (3/31), respectively. The live birth rate after in vitro fertilization was 25.8% (8/31) in the isthmoplasty group and 3.3% (1/30) in the control group (p < 0.05). There were no significant differences in the IVF outcomes such as the biochemical pregnancy rate and miscarriage rate between the isthmoplasty and control groups. This study demonstrated that hysteroscopic isthmoplasty improves pregnancy and live birth rates for women with a history of RIF and isthmocele. Reproductive results of the IVF cycles after hysteroscopic correction of isthmocele were comparable to those of the patients without any uterine abnormalities and those with diagnosis of unexplained infertility.

Endometriosis and oocyte quality: an analysis of 13 614 donor oocyte recipient and autologous IVF cycles.

STUDY QUESTIONDoes endometriosis affect live birth following donor oocyte recipient versus autologous IVF?SUMMARY ANSWERThere was no significant difference in the live birth rate (LBR) in women with endometriosis undergoing donor oocyte recipient cycles versus autologous IVF cycles.WHAT IS KNOWN ALREADYFor infertile women with endometriosis, IVF is often considered as a treatment option. Lower implantation and pregnancy rates have been observed following IVF in women with endometriosis. It has been debated whether the lower pregnancy rate is due to the effect on oocyte quality or the endometrium, thus affecting implantation. To delineate whether endometriosis affects oocyte quality or the endometrium, we planned a study, using a donor oocyte recipient model, where the recipients were women diagnosed with endometriosis and compared their outcomes with women who underwent autologous IVF, who had also been diagnosed with endometriosis.STUDY DESIGN, SIZE, DURATIONHuman Fertilization and Embryology Authority (HFEA) anonymized data from 1996 to 2016 were analyzed. This comprised of a total of 758 donor oocyte recipients, where the recipients were women diagnosed with endometriosis, and 12 856 autologous IVF cycles where the women were diagnosed with endometriosis as the sole cause of infertility.PARTICIPANTS/MATERIALS, SETTING, METHODSData on all women with endometriosis undergoing donor oocyte recipient and autologous IVF cycles were analyzed to compare live birth outcomes. Logistic regression analysis was performed adjusting for number of previous IVF cycles, previous live birth, period of treatment, day of embryo transfer, number of embryos transferred and fresh or frozen embryo transfer cycle.MAIN RESULTS AND THE ROLE OF CHANCEThere was no significant difference in the LBR in women with endometriosis undergoing donor oocyte recipient fresh embryo transfer cycles compared to women undergoing autologous IVF fresh embryo transfer cycles (31.6% vs 31.0%; odds ratio (OR) 1.03, 99.5% CI 0.79–1.35). After adjusting for confounders, there was no significant difference in LBR in women with endometriosis undergoing donor oocyte recipient fresh embryo transfer cycles versus autologous fresh embryo transfer cycles (adjusted OR (aOR) 1.05, 99.5% CI 0.79–1.41).There was no significant difference in the LBR in women with endometriosis undergoing donor oocyte recipient frozen embryo transfer cycles compared to women undergoing autologous frozen embryo transfer cycles (19.6% vs 24.0%; OR 0.77, 99.5% CI 0.47–1.25). After adjusting for potential confounders, there was no significant difference in the LBR in women undergoing donor oocyte recipient frozen embryo transfer cycles compared with autologous frozen embryo transfer cycles (aOR 0.85, 99.5% CI 0.51–1.41).LIMITATIONS, REASONS FOR CAUTIONAlthough the analysis was adjusted for potential confounders, there was no information on the extent and classification of endometriosis as well as oocyte number. Furthermore, adenomyosis is thought to co-exist in women with endometriosis and may have independent pathophysiological mechanisms affecting fertility, for which there was no information.WIDER IMPLICATIONS OF THE FINDINGSThe study shows no difference in LBR between donor oocyte recipient cycles in which all recipients had endometriosis compared to autologous IVF cycles in women with endometriosis. Therefore, this study finding suggests that there may be a minimal or no effect of oocyte quality on IVF outcomes in women with endometriosis.STUDY FUNDING/COMPETING INTEREST(S)No funding was obtained. M.S.K. is an associate editor with Human Reproduction Open. He was not involved in the editorial or peer review process for the manuscript.TRIAL REGISTRATION NUMBERN/A.

The impact of biparental hepatitis B virus infection on pregnancy outcomes in patients undergoing assisted reproductive technology treatment: a systematic review and meta-analysis.

To evaluate the association between biparental hepatitis B virus (HBV) infection (hepatitis B surface antigen [HBsAg] seropositivity) and pregnancy outcomes in patients undergoing assisted reproductive technology (ART) treatment, including clinical pregnancy rate (CPR) and live birth rate (LBR). We searched various literature databases from the earliest date available until May 20, 2021, including PubMed, Embase, Medline, Web of Science, Scopus, CNKI, and Wangfang. Four patterns of biparental HBV infection for pregnancy outcomes following ART were synthesized separately by using random-effects model. We also performed subgroup analyses (matched or unmatched) and two forms of sensitivity analysis. A total of 25 retrospective cohort studies, involving more than 19,269 couples, were included. Maternal and paternal HBV co-infection (crude relative risk [cRR]: 0.58, 95% confidence interval: 0.28-1.23), either maternal or paternal infection (cRR: 1.05, 0.88-1.24), maternal HBV infection alone (cRR: 0.96, 0.79-1.16), or paternal HBV infection alone (cRR: 1.02, 0.91-1.13) were not associated with significant reductions in CPR at per woman level. These patterns of infection were also not significantly associated with decreased LBR at per woman level. However, paternal HBV infection alone reduced CPR (adjusted odds ratio: 0.54, 0.33-0.86) and LBR (cRR: 0.52, 0.28-0.99) at per cycle level. Subgroup analyses and sensitivity analyses were mostly consistent with the primary results. Paternal HBV infection alone probably decrease CPR after ART at per cycle level. However, maternal HBV infection was not associated with reductions in CPR and LBR in women undergoing ART at per woman level.

Are There Ovarian Responsive Indexes That Predict Cumulative Live Birth Rates in Women over 39 Years?

Objective: Ovarian response indexes have been proposed in assisted reproductive technology (ART) in order to optimize live birth rates (LBR), adjusting ovarian stimulation (OS), and minimizing risks. Gonadotropin doses are commonly adjusted according to ovarian reserve parameters, including antral follicle count (AFC), anti-Mullerian hormone (AMH), and basal follicle stimulating hormone (FSH) levels. The retrospective assessment of ovarian responses allows one to identify three primary indexes: (i) follicular output rate (FORT), the ratio of the number of pre-ovulatory follicles obtained at OS completion over AFC; (ii) follicle oocyte index (FOI), the ratio of oocytes retrieved over AFC; (iii) ovarian sensitivity index (OSI), the ratio of oocytes retrieved over the total gonadotropin dose administered. In recent publications, these indexes were reported to predict ART outcome. In the present study, we assessed the ability of these indexes to predict cumulative ART outcome in women ≥39 years. Materials and Methods: Retrospective cohort study. All patients ≥39 years who performed their first ART cycle with an antagonist protocol in our center between 01/2018 and 04/2020 were included. Patients with basal FSH > 20 IU/l, AMH < 0.1 ng/mL and severe male factors (azoospermia with testicular biopsy) were excluded. All patients received both recombinant FSH and human menopausal gonadotropin (hMG). Cumulative live birth rate (cLBR) was the primary outcome. Secondary outcomes included: the number of MII oocytes, cumulative implantation (cIR), and usable blastulation rates. Logistic regressions were performed to assess the predictive values of FORT, FOI, and OSI in cLBR and embryo culture success. For each parameter, the ability of the logistic regression models to predict embryo culture success was quantified by the area under the ROC curve (AUC). Only the significant findings related to FORT, FOI, and OSI were included in the multiple logistic regression model. Linear regression models were performed between cIR, cLB, FORT, FOI, and OSI. Each statistic model was adjusted for age. Concerning OR for OSI, values were multiplied *100 due to the very low value. Results: 429 patients met the inclusion criteria. There were 298 obtained usable blastocysts after ART treatment. Age-adjusted OSI was significantly associated with cLBR [OR = 17.58 95% CI (5.48–56.40), AUC = 0.707 95% CI (0.651–0.758)) and cIR (beta = 30.22 (SE: 7.88), p < 0.001, R2= 0.060). Both FOI (OR = 6.33 95% CI (3.27–12.25), AUC = 0.725 95% CI (0.675–0.771), R2 = 0.090, p < 0.001) and OSI (OSI*100; OR = 1808.93 95% CI (159.24–19,335.13), AUC = 0.790 95% CI (0.747–0.833), R2 = 0.156, p < 0.001) were independently, when age adjusted, associated with embryo culture success. OSI showed a main performance to explain successful embryo culture than FOI (R2 = 0.156 vs. R2 = 0.090, p < 0.001). In the age-adjusted linear regression model, FOI (R2 = 0.159, p < 0.001), OSI (R2 = 0.606, p < 0.001), and FORT (r2 = 0.030, p < 0.001) were predictive of the number of MII oocytes collected. Furthermore, for OSI (r2 = 0.759, p < 0.001) and FOI (r2 = 0.297, p < 0.001), the correlation with the number of metaphase II oocytes collected was significantly higher in the non-linear regression model. Conclusions: Our findings suggest that the best index, among those analyzed, to predict cIR and cLBR, is OSI. Both OSI and FOI predict embryo culture with success, but OSI is more accurate. OSI, FOI, and FORT are significantly related to the number of MII oocytes obtained.

Live Birth Rate in Women with Recurrent Pregnancy Loss after In Vitro Fertilization with Concomitant Intravenous Immunoglobulin and Prednisone.

Pregnancy loss after in vitro fertilization (IVF) is at least as common as after spontaneous conception. Recurrent pregnancy loss (RPL) may often have an immunological background, and it is therefore relevant to test immune-based interventions in these patients. The objective was to investigate the effect of immunotherapy with intravenous immunoglobulin (IvIg) and prednisone (PRS) as concomitant therapy to IVF in women with RPL after earlier IVF treatments. In a cohort study conducted at The Danish RPL Clinic, 41 women with three or more consecutive pregnancy losses after IVF underwent at least one further IVF cycle with concomitant immunotherapy from 2012 to 2017. The immunotherapy with IvIg and PRS was given before embryo transfer and repeatedly in the first trimester when pregnancy was achieved. Fourteen women (34.2%) achieved a live birth after the first embryo transfer with immunotherapy, and a total of 32/41 (78%) achieved a live birth after up to 4 embryo transfers. Baseline characteristics and the presence of autoantibodies were not significantly different among women achieving live birth or not. The observed 34% birth rate in women with RPL after IVF receiving immunotherapy appears higher than the expected 16–19% birth rate without immunotherapy and is similar to findings in a previous cohort from our clinic. Concomitant immunotherapy as described may be a promising intervention for women with RPL after IVF; however, the effect must be tested in a randomized controlled trial.

Effect of autologous platelet-rich plasma for treatment of recurrent pregnancy loss: a randomized controlled trial.

ObjectiveRecurrent pregnancy loss (RPL) is a fertility problem for which no exact mechanism of abortion or efficient treatment has been described. This study was conducted between 2018 and 2019 to investigate the effectiveness of autologous platelet-rich plasma (PRP) in improving the live birth rate of women with RPL who required in vitro fertilization (IVF).MethodsA total of 63 patients with at least two previous pregnancy losses and no specific cause detected for the RPL were included and randomly assigned into two groups (PRP and control). Intrauterine infusion of 0.5 mL of autologous PRP was performed 48 hours before embryo transfer in the PRP group. Women in the control group received standard treatment.ResultsForty patients completed the study. The baseline and cycle characteristics of the participants did not differ significantly between the PRP and control groups. The clinical pregnancy rate was higher in the PRP group (35% vs. 20%, P=0.288). The live birth rate was 15% in the PRP group, but no live births were recorded in the control group (P=0.231).ConclusionThis is the first study to show that intrauterine infusion of PRP in patients with RPL who undergo IVF may increase the chance of live birth.

Levothyroxine in euthyroid thyroid peroxidase antibody positive women with recurrent pregnancy loss (T4LIFE trial): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial

Women positive for thyroid peroxidase antibodies (TPO-Ab) have a higher risk of recurrent pregnancy loss. Evidence on whether levothyroxine treatment improves pregnancy outcomes in women who are TPO-Ab positive women with recurrent pregnancy loss is scarce. The aim of this study was to determine if levothyroxine increases live birth rates in women who were TPO-Ab positive with recurrent pregnancy loss and normal thyroid function. The T4LIFE trial was an international, double-blind, placebo-controlled, phase 3 study done in 13 secondary and tertiary hospitals in the Netherlands, one tertiary hospital in Belgium, and one tertiary hospital in Denmark. Women (18-42 years) who were TPO-Ab positive, had two or more pregnancy losses, and had a thyroid stimulating hormone (TSH) concentration within the institutional reference range were eligible for inclusion. Women were excluded if they had antiphospholipid syndrome (lupus anticoagulant, anticardiolipin IgG or IgM antibodies, or β2-glycoprotein-I IgG or IgM antibodies), other autoimmune diseases, thyroid disease, previous enrolment in this trial, or contraindications for levothyroxine use. Before conception, women were randomly assigned (1:1) to receive either levothyroxine or placebo orally once daily. The daily dose of levothyroxine was based on preconception TSH concentration and ranged from 0·5-1·0 μg/kg bodyweight. Levothyroxine or placebo was continued until the end of pregnancy. The primary outcome was live birth, defined as the birth of a living child beyond 24 weeks of gestation measured in the intention-to-treat population. The trial was registered within the Netherlands Trial Register, NTR3364 and with EudraCT, 2011-001820-39. Between Jan 1, 2013, and Sept 19, 2019, 187 women were included in the study: 94 (50%) were assigned to the levothyroxine group and 93 (50%) were assigned to the placebo group. The trial was prematurely stopped when 187 (78%) of the 240 predefined patients had been included because of slow recruitment. 47 (50%) women in the levothyroxine group and 45 (48%) women in the placebo group had live births (risk ratio 1·03 [95% CI 0·77 to 1·38]; absolute risk difference 1·6% [95% CI -12·7 to 15·9]). Seven (7%) women in the levothyroxine group and seven (8%) in the placebo group reported adverse events, none of them were directly related to the study procedure. Compared with placebo, levothyroxine treatment did not result in higher live birth rates in euthyroid women with recurrent pregnancy loss who were positive for TPO-Ab. On the basis of our findings, we do not advise routine use of levothyroxine in women who are TPO-Ab positive with recurrent pregnancy loss and normal thyroid function. Dutch Organization for Health Research and Development, Fonds NutsOhra, Dutch Patient Organization of Thyroid Disorders, the Jan Dekkerstichting and Dr Ludgardine Bouwmanstichting, and a personal donation through the Dutch Patient Organization of Thyroid Disorders.