Similar Live Birth Rates Research Articles

Thyroxine replacement for subfertile women with euthyroid autoimmune thyroid disease or subclinical hypothyroidism.

Thyroid disease is the second most common endocrine disorder affecting women of reproductive age. Subclinical hypothyroidism is diagnosed by an elevated thyroid-stimulating hormone concentration with a normal concentration of free thyroxine hormone. Autoimmune thyroid disease (ATD) is diagnosed by the presence of thyroid autoantibodies, regardless of thyroid hormone levels. Thyroxine may be a useful treatment for subfertile women with these two specific types of thyroid disease for improving pregnancy outcomes during assisted reproduction. To evaluate the efficacy and harms of levothyroxine replacement in subfertile women with subclinical hypothyroidism or with normal thyroid function and thyroid autoimmunity (euthyroid autoimmune thyroid disease, or euthyroid ATD) undergoing assisted reproduction. We searched the Cochrane Gynaecology and Fertility (CGF) Group specialised register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL and two trials registers together with reference checking and contact with study authors and experts in the field to identify studies. We searched for all published and unpublished randomised controlled trials (RCTs) comparing thyroxine with no treatment or placebo, without language restrictions, from inception to 8 April 2019, and in consultation with the Cochrane CGF Information Specialist. We included women undergoing assisted reproduction treatment, meaning both in vitro fertilisation and intracytoplasmic sperm injection, with a history of subfertility and with subclinical hypothyroidism or with euthyroid ATD. We excluded women with a previously known clinical hypothyroidism or already taking thyroxine or tri-iodothyronine. RCTs compared thyroxine (levothyroxine) with either placebo or no treatment. We used standard methodological procedures expected by Cochrane. Our primary review outcomes were live birth and adverse events of thyroxine; our secondary outcomes were clinical pregnancy, multiple pregnancy and miscarriage. The review included four studies with 820 women. The included studies were of overall low risk of bias. Using GRADE methodology, we assessed the quality of evidence for the primary outcomes of this review to be very low- to low-quality evidence. Evidence was downgraded for imprecision as it was based on single, small trials with wide confidence intervals (CI). We were able to include data from three of the four included studies.In one study of women with both subclinical hypothyroidism and positive or negative anti-TPO antibodies (autoimmune disease), the evidence suggested that thyroxine replacement may have improved live birth rate (RR 2.13, 95% CI 1.07 to 4.21; 1 RCT, n = 64; low-quality evidence) and it may have led to similar miscarriage rates (RR 0.11, 95% CI 0.01 to 1.98; 1 RCT, n = 64; low-quality evidence). The evidence suggested that women with both subclinical hypothyroidism and positive or negative anti-TPO antibodies would have a 25% chance of a live birth with placebo or no treatment, and that the chance of a live birth in these women using thyroxine would be between 27% and 100%.In women with normal thyroid function and thyroid autoimmunity (euthyroid ATD), treatment with thyroxine replacement compared with placebo or no treatment may have led to similar live birth rates (risk ratio (RR) 1.04, 95% CI 0.83 to 1.29; 2 RCTs, number of participants (n) = 686; I2 = 46%; low-quality evidence) and miscarriage rates (RR 0.83, 95% CI 0.47 to 1.46, 2 RCTs, n = 686, I2 = 0%; low-quality evidence). The evidence suggested that women with normal thyroid function and thyroid autoimmunity would have a 31% chance of a live birth with placebo or no treatment, and that the chance of a live birth in these women using thyroxine would be between 26% and 40%.Adverse events were rarely reported. One RCT reported 0/32 in the thyroxine replacement group and 1/32 preterm births in the control group in women diagnosed with subclinical hypothyroidism and positive or negative anti-TPO antibodies. One RCT reported 21/300 preterm births in the thyroxine replacement group and 19/300 preterm births in the control group in women diagnosed with positive anti-TPO antibodies. None of the RCTs reported on other maternal pregnancy complications, foetal complications or adverse effects of thyroxine. We could draw no clear conclusions in this systematic review due to the very low to low quality of the evidence reported.

Cumulative live birth rates following a 'freeze-all' strategy: a population-based study.

STUDY QUESTIONWhat is the cumulative live birth rate following a ‘freeze-all’ strategy compared with a ‘fresh-transfer’ strategy?SUMMARY ANSWERThe ‘freeze-all’ strategy resulted in a similar cumulative live birth rate as the ‘fresh-transfer’ strategy among high responders (>15 oocytes retrieved) but did not benefit normal (10–15 oocytes) and suboptimal responders (<10 oocytes).WHAT IS KNOWN ALREADYFrozen-thawed embryo transfer is associated with a decreased risk of adverse obstetric and perinatal outcomes compared with fresh embryo transfer. It is unclear whether the ‘freeze-all’ strategy should be offered to all women undergoing ART treatment.STUDY DESIGN, SIZE, DURATIONA population-based retrospective cohort study using data collected by the Victorian Assisted Reproductive Treatment Authority. This study included 14 331 women undergoing their first stimulated ART cycle with at least one oocyte fertilised between 1 July 2009 and 30 June 2014 in Victoria, Australia. Demographic characteristics, type of ART procedures and resulting pregnancy and birth outcomes were recorded for the stimulated cycle and associated thaw cycles until 30 June 2016, or until a live birth was achieved, or until all embryos from the stimulated cycle had been used.PARTICIPANTS/MATERIALS, SETTING, METHODSWomen were grouped by whether they had undergone the ‘freeze-all’ strategy (n = 1028) where all embryos were cryopreserved for future transfer, or the ‘fresh-transfer’ strategy (n = 13 303) where selected embryo(s) were transferred in the stimulated cycle, and remaining embryo(s) were cryopreserved for future use. A discrete-time survival model was used to evaluate the cumulative live birth rate following ‘freeze-all’ and ‘fresh-transfer’ strategy.MAIN RESULTS AND THE ROLE OF CHANCEA total of 1028 women undergoing ‘freeze-all’ strategy and 13 303 women undergoing ‘fresh-transfer’ strategy had 1788 and 22 334 embryo transfer cycles resulting in 452 and 5126 live births, respectively. Most women (61.3%) in the ‘freeze-all’ group had more than 15 oocytes retrieved in the stimulated cycle compared with 18.1% of women in the ‘fresh-transfer’ group (P < 0.001). For high responders (>15 oocytes), the cumulative live birth rate in the ‘freeze-all’ group was similar to the ‘fresh-transfer’ group (56.8% vs. 56.2%, adjusted hazard ratio (AHR) 0.90, 95% CI 0.77–1.04). However, the likelihood of a live birth was lower in the ‘freeze-all’ group compared with the ‘fresh-transfer’ group among normal responders (10–15 oocytes) (33.2% vs. 46.3%, AHR 0.62, 95% CI 0.46–0.83) and suboptimal responders (<10 oocytes) (14.6% vs. 28.0%, AHR 0.67, 95% CI 0.14–1.01). During the minimum follow-up time of 2 years, 34.1%, 24.4% and 8.4% of suboptimal, normal and high responders, respectively, in the ‘freeze-all’ group did not return for any embryo transfer after the stimulated cycle, whereas all women in the ‘fresh-transfer’ group had at least one embryo transferred in the stimulated cycle.LIMITATIONS REASONS FOR CAUTIONA limitation of this population-based study is the lack of information available on clinic-specific protocols for the ‘freeze-all’ strategy and the potential impact of these on outcomes. Data were not available on whether the ‘freeze-all’ strategy was used to prevent ovarian hyperstimulation syndrome (OHSS).WIDER IMPLICATIONS OF THE FINDINGSThis study presents population-based evidence on clinical efficacy associated with a ‘freeze-all’ and ‘fresh-transfer’ strategy. The ‘freeze-all’ strategy may benefit some subgroups of patients, including women who are high responders and those who are at risk of OHSS, but should not be offered universally. Clinicians should consider the potential impact of electively deferring embryo transfer on treatment discontinuation in choosing the optimal embryo transfer strategy for couples undergoing ART treatment.STUDY FUNDING/COMPETING INTEREST(S)No specific funding was received to undertake this study. There is no conflict of interest, except that M.B. is a shareholder in Genea Ltd.

Live Birth Rates in In vitro Fertilization Cycles with Oocytes Containing Smooth Endoplasmic Reticulum Aggregates and Normal Oocytes.

Aims:The aims of this study were to compare the live birth, embryological and pregnancy outcomes after intracytoplasmic sperm injection (ICSI) in patients who have oocytes with smooth endoplasmic reticulum aggregates (SERa+ cycles) and patients with normal oocytes and to compare the pregnancy outcomes based on the observed frequency of SERa.Settings and Design:The current study was a retrospective case record review of patients undergoing ICSI from 2012 to 2016 in a specialty fertility center.Materials and Methods:The patients were divided into two groups based on the presence of SERa: patients with at least one oocyte containing SERa (SERa+ cycles) (n = 112) and patients with normal oocytes (n = 839). The primary outcome measure was live birth rate. The secondary outcome measures were fertilization rate, cleavage rate, blastocyst formation rate, clinical pregnancy rate, miscarriage rate, and anomalies in children born.Results:Women with SERa+ cycles showed similar live birth rates, fertilization rates, cleavage rates, blastocyst formation rates, clinical pregnancy rates, miscarriage rates, and abnormalities in children compared to women with normal oocytes. A gradual reduction in live birth rates was observed when the percentage of oocytes containing SERa increased. The group containing >50% of oocytes with SERa demonstrated no live births.Conclusions:Presence of SERa had no major overall negative impact on key embryological and live birth outcomes. A reduction in the live birth rate with increasing proportion of SERa oocytes was observed, with no live births in the group with >50% or all affected oocytes.

Comparison between Single and Double Cleavage-Stage Embryo Transfers, Single and Double Blastocyst Transfers in a South East Asian In Vitro Fertilisation Centre

This study investigated the differences in clinical pregnancy rate (CPR), live birth rate (LBR) and multiple pregnancy rate (MPR) between double cleavage-stage embryo transfers compared to single and double blastocysts stage embryo transfers in a single academic medical centre. This was a retrospective cohort study performed at the KK Women's and Children's Hospital In Vitro Fertilisation (KKIVF) Centre of all women who underwent fresh-cycle in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) cycles over a 5-year period. The outcome measures were CPR, LBR and MPR. The study included 5294 cycles, of which 539 patients underwent single embryo transfer (SET); 4533 patients underwent double embryo transfer (DET); 84 patients underwent double blastocyst embryo transfer (DBT); and 65 patients underwent single blastocyst embryo transfer (SBT). The mean age of patients undergoing single blastocysts stage embryo transfer was lower than the other 2 groups. The DET, single and double blastocysts stage embryo transfer groups achieved similar LBR (33.9%, 38.7%, 35.4%, P >0.05) and CPR (42.4%, 46.2%, 46.9%). We found that single blastocysts stage embryo transfer is associated with similar LBR and CPR compared to double blastocysts stage embryo transfer and DET, with lower MPRs, and should be offered as standard practice, where possible.

New therapeutic protocol for improvement of endometrial receptivity (PRIMER) for patients with recurrent implantation failure (RIF) - a pilot study

Objective To evaluate whether or not one should use a new Protocol for Endometrial Receptivity Improvement (PRIMER) based on platelet-rich plasma (PRP) and granulocyte colony-stimulation factor (G-CSF) to enhance ongoing pregnancy rates in patients with recurrent implantation failure (RIF). Methods Women undergoing IVF/ICSI were prospectively divided into two groups: - PRIMER/RIF group (n:33): patients with RIF (defined as ≥2embryo transfers (ETs) and at least 5 morphologically good embryos transferred) in which intrauterine PRP injection and subcutaneous G-CSF-injection were performed. - Control group (n:33): patients in their first IVF/ICSI attempt/cycle (without PRP or G-CSF injection). The PRP was prepared using autologous fresh-whole blood processed to increase platelet-concentration in 2 to 4 fold. All patients undergoing the PRP-treatment received 0.7ml of it through intrauterine-injection 48 hours before the ET. G-CSF (300mg/0.5ml) started simultaneously to PRP and was administered subcutaneously every week. Results Regarding implantation, clinical pregnancy and miscarriage rates, we found no statistically significant difference (18.2% versus 17.6%, p=0.90; 36.4% versus 30.3%, p=0.61 and 25.0% versus 9.0%, p=0.43, respectively). The use of PRIMER enabled RIF patients (previous ET µ: 4.0±1.5) to reach similar ongoing pregnancy and live birth rates like those patients who had their first IVF/ICSI cycle attempt (27.3% versus 27.3%, p=0.99). Conclusions Our results showed, for the first time, evidence that this therapeutic protocol (PRIMER) could be used as a feasible treatment based on biological rationale for patients with RIF, considering its promising outcomes, it is a simple procedure and not associated with patient complications.

Hysteroscopic Endometrial Focal Resection followed by Levonorgestrel Intrauterine Device Insertion as a Fertility-Sparing Treatment of Atypical Endometrial Hyperplasia and Early Endometrial Cancer: A Retrospective Study

Study ObjectiveTo evaluate safety and effectiveness of the combination of hysteroscopic endometrial focal resection with levonorgestrel-releasing intrauterine device (LNG-IUD) for International Federation of Gynecology and Obstetrics stage IA G1 early endometrial cancer (EEC) and atypical endometrial hyperplasia (AEH) in young women to preserve their fertility. DesignRetrospective case series (Canadian Task Force classification II-3). SettingUniversity Federico II, Naples, Italy. PatientsThe medical records of 69 consecutive patients treated from 2007 to 2017 with diagnosis of EEC (n = 14) or AEH (n = 55) meeting inclusion criteria were reviewed. InterventionsPatients with focal EEC were treated by hysteroscopic resection of the lesion according to Mazzon's technique; patients with AEH were treated by superficial endometrial resection, preserving the basal layer of the endometrium. An LNG-IUD was inserted in all patients after surgery. Patients were followed for 24 months with serial hysteroscopic biopsies. Measurements and Main ResultsRates of response, live birth, and recurrence were assessed. Of the 14 patients with EEC, 11 (78.6%) achieved a complete response, 2 (18.2%) of whom had subsequent relapse, 1 (7.1%) showed partial response, whereas 2 (14.3%) were nonresponders (1 stable disease and 1 progression). Of the 55 patients with AEH, 51 (92.7%) achieved a complete response, 2 (3.9%) of whom had subsequent relapse, 3 (5.5%) showed partial response, whereas only 1 (1.8%) was nonresponder with stable disease. Among 25 patients who had removed the LNG-IUD, 10 (40%) gave birth after natural conception in the last 12 months of follow-up. ConclusionThe combination of hysteroscopic resection with an LNG-IUD as fertility-sparing treatment of EEC and AEH showed similar response and live birth rates compared with those reported in literature for progestins alone, but with considerably lower relapse rate. We advocate the use of this combined approach as an alternative fertility-sparing option in patients with ECC and AEH.

Non-Invasive Markers (ALBI and APRI) Predict Pregnancy Outcomes in Women With Chronic Liver Disease.

Rates of pregnancy in women with cirrhosis are increasing. Risk of hepatic decompensation during pregnancy, therefore, merits tailored obstetric and hepatology care. Prognostic markers that determine pregnancy outcomes are lacking. Medical records of women who attended hepatology clinic at King's College Hospital with chronic liver disease (CLD) who became pregnant from 1983 to 2017 were reviewed. Information on demographics, clinical history, serology, and outcome of pregnancy was collected. In all, 165 pregnancies occurred in 100 women with CLD including 80 pregnancies in 48 women with cirrhosis. Median age of conception in cirrhotic and non-cirrhotic women were 26 years (16-44) and 28 years (16-51) respectively (p = 0.015). Whilst women with cirrhosis had similar live birth rate to non-cirrhotic women (75 vs. 85% p = 0.119), they were significantly less likely to proceed beyond 37 weeks gestation (45 vs. 58% p = 0.033). Women who received preconception counseling were more likely to have stable liver disease at conception (100 vs 86% p = 0.02). Compared with preconception MELD (model for end stage liver disease), preconception Albumin-Bilirubin score (ALBI) more accurately predicted live birth with an area under the receiver-operator curve (AUROC) of 0.741 (p < 0.001), and preconception AST to platelet ratio index (APRI) more accurately predicted ability to proceed beyond 37 weeks gestation with an AUROC of 0.700 (p < 0.001). Most women with cirrhosis who conceived achieved a successful pregnancy outcome. ALBI and APRI scores can prognosticate pregnancy outcomes in women with CLD. Preconception counseling by a hepatologist or specialist obstetrician improved patient care in this group.

Freeze-all embryo strategy in poor ovarian responders undergoing ovarian stimulation for in vitro fertilization

This retrospective study determined the efficacy of the ‘freeze-all’ embryo strategy in poor ovarian responders undergoing ovarian stimulation for in vitro fertilization (IVF). A total of 559 poor responders who met Bologna criteria between January 2012 and December 2014 were included in this study: 256 in the fresh embryo transfer group and 303 in the freeze-all group. Vitrification and warming of day 3 embryos were performed using the Cryotop method. The poor responders treated with fresh embryo transfer and those treated with freeze-all strategy showed similar live birth rates per cycle (12.1% vs. 16.2%, p = .172) and per transfer (15.9% vs. 20.9%, p = .182). Multivariate logistic regression analysis showed that maternal age at retrieval (odds ratio, 0.919; 95% confidence interval, 0.865–0.977; p = .006) and number of good-quality embryos transferred (odds ratio, 1.953; 95% confidence interval, 1.346–2.835; p < .001) were significantly associated with the live birth rate. Freeze-all cycle is an acceptable treatment in poor ovarian responders, and it should be suggested by physicians as an alternative to cycle cancelation in case in which a fresh transfer would not be advantageous.

Http://www.jirb.dormaj.com/issues/Volume%205,%20Issue%204/Anti-Coagulant%20Therapy%20in%20Unexplained%20Recurrent%20Pregnancy%20Loss.pdf

Recurrent pregnancy loss (RPL) is a heterogeneous reproductive problem with multiple aetiologies and contributing factors. It becomes quite challenging to form a work-up to detect the cause of RPL in the early months as a continuation of pregnancy involves many factors. In more than half of all recurrent miscarriage the cause still remains uncertain. Thrombophilia has been identified in about 50% of women with recurrent miscarriage and thromboprophylaxis has been suggested as an option of treatment.. In obstetric APLA Syndrome (Antiphospholipid antibody) the combination of aspirin and heparin has improved outcomes. The use of low molecular weight heparin (LMWH) has become a common practise in women with inherited thrombophilia and also those with unexplained miscarriage to help safeguard the ongoing pregnancy. To evaluate if there is any effectiveness of low molecular weight heparin (enoxaparin) in women with a history of at least two miscarriages without any apparent aetiology for recurrent pregnancy loss. A prospective randomised controlled study held at Vivekananda Institute of Medical Sciences, Kolkata from August 2015- July 2018. The study assessed the effect of anticoagulant treatment on the live-birth rate (primary outcome) in 80 antenatal women with a history of at least two miscarriages without any apparent causes. Interventions included low molecular weight heparin administration in one group and the other one was not given any anti-coagulant therapy. Similar live birth rates were observed with enoxaparin and the patients who did not receive any anti-coagulant, respectively 84% and 82% (RR 0.97, 95% CI 0.81 to 1.16). There were no significant differences in live birth weight and other pregnancy outcomes between the two groups. Therefore, there is no evidence to support any incremental benefit of adding LMWH to the treatment as a routine in unexplained cases of recurrent pregnancy loss.

Effect of the male factor on the clinical outcome of intracytoplasmic sperm injection combined with preimplantation aneuploidy testing: observational longitudinal cohort study of 1,219 consecutive cycles

To evaluate the impact of the male factor on the outcomes of intracytoplasmic sperm injection (ICSI) cycles combined with preimplantation genetic testing for aneuploidies (PGT-A). Observational longitudinal cohort study. Private invitro fertilization (IVF) center. A total of 1,219 oocyte retrievals divided into five study groups according to sperm parameters: normozoospermia (N), moderate male factor (MMF), severe oligoasthenoteratozoospermia (OAT-S), obstructive azoospermia (OA), and nonobstructive azoospermia (NOA). ICSI with ejaculated/surgically retrieved sperm, blastocyst culture, trophectoderm-based quantitative polymerase chain reaction PGT-A, and frozen-warmed euploid embryo transfer (ET). The primary outcome measures were fertilization, blastocyst development, and euploidy rates; the secondary outcome measures were live birth and miscarriage rates. Perinatal and obstetrical outcomes were monitored as well. A total of 9,042 metaphase II oocytes were inseminated. The fertilization rate was significantly reduced in MMF, OAT-S, OA, and NOA compared with N (74.8%, 68.7%, 67.3%, and 53.1% vs. 77.2%). The blastocyst rate per fertilized oocyte was significantly reduced in MMF and NOA compared with N (48.6% and 40.6% vs. 49.3%). The timing of blastocyst development also was affected in OA and NOA. Logistic regression analysis adjusted for confounders highlighted NOA as a negative predictor of obtaining an euploid blastocyst per OPU (odds ratio 0.5). When the analysis was performed per obtained blastocyst, however, no correlation between male factor and euploidy rate was observed. Embryo transfers also resulted in similar live birth and miscarriage rates. No impact of sperm factor on obstetrical/perinatal outcomes was observed. Severe male factor impairs early embryonic competence in terms of fertilization rate and developmental potential. However, the euploidy rate and implantation potential of the obtained blastocysts are independent from sperm quality.

Clomiphene citrate and letrozole to reduce follicle-stimulating hormone consumption during ovarian stimulation: systematic review and meta-analysis.

To assess the available evidence comparing effectiveness of ovarian stimulation (OS) using clomiphene citrate (CC) and/or letrozole (LTZ) to reduce follicle-stimulating hormone (FSH) consumption compared with standard OS. We performed a systematic review and meta-analysis of randomized controlled trials that compared reproductive outcomes following in-vitro fertilization. We searched 11 electronic databases and hand-searched the reference lists of included studies and related reviews. We stratified the results, separating studies according to the oral agent used (CC or LTZ) and the characteristics of the included women (expected poor ovarian response or other women). When combining the results of the included studies, we assessed the relative risk (RR) for live birth, clinical pregnancy, miscarriage and cycle cancelation, the Peto odds ratio (OR) for ovarian hyperstimulation syndrome (OHSS) and mean difference (MD) for the number of oocytes retrieved and FSH consumption. A total of 22 studies were included in the review. Considering women with expected poor ovarian response, the available evidence suggested that using CC to reduce FSH consumption during OS provided similar rates of live birth (RR, 0.9 (95% CI, 0.6-1.2), moderate-quality evidence) and clinical pregnancy (RR, 1.0 (95% CI, 0.8-1.4), moderate-quality evidence); the use of LTZ did not cause a relevant change in the number of oocytes retrieved (MD, -0.4 (95% CI, -0.9 to 0.1), high-quality evidence). Considering the studies evaluating other women, the available evidence suggested that using CC to reduce FSH consumption during OS reduced the number of oocytes retrieved (MD, -4.6 (95% CI, -6.1 to -3.0), high-quality evidence) and risk of OHSS (Peto OR, 0.2 (95% CI, 0.1-0.3), moderate-quality evidence), while results were similar for rates of live birth (RR, 0.9 (95% CI, 0.7-1.1), moderate-quality evidence) and clinical pregnancy (RR, 1.0 (95% CI, 0.8-1.1), high-quality evidence). The quality of the evidence was low or very low for other outcomes. The use of CC to reduce FSH consumption in women with expected poor ovarian response has the advantage of providing similar reproductive outcomes with reduced costs. For the other women, the use of CC for reducing FSH consumption has the additional advantage of reducing OHSS, but also reduces the total number of oocytes retrieved. More studies are needed to evaluate the effect of LTZ for the same purpose. Future studies should focus on cumulative pregnancy per oocyte retrieval, patient dissatisfaction and agreement to repeat the cycle if not pregnant, which are important outcomes for clinical decisions. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Which is worse? A comparison of ART outcome between women with primary or recurrent endometriomas.

Study question Are live birth rates (LBR) different after ART cycles between women with primary or recurrent endometrioma? Summary answer Women with recurrent endometrioma have similar LBR as compared to patients with primary endometrioma. What is already known Recurrence rate can be as high as 29% after endometrioma excision. Prior studies on management of endometrioma before ART involve primary endometriomas. There is limited information regarding the prognosis of women with recurrent endometriomas. Study design, size, duration A multicenter retrospective cohort study, including 76 women with primary and 82 women with recurrent endometriomas treated at the participating centers over a 6-year period. Participants/materials, setting, methods Women with endometrioma who underwent ART at three academic ART centers. Couples with another indication for ART were excluded. Main results and the role of chance Female age, median number of prior failed ART cycles, proportion of patients with bilateral endometrioma (28 versus 28.9%), ovarian stimulation protocols, and total gonadotropin consumption were similar between the study groups. Numbers of metaphase two oocytes (5 versus 6), number of embryos transferred, and the proportion of patients undergoing blastocyst transfer were similar across the study groups. Clinical pregnancy rates (36.6 versus 34.2%, absolute difference 2.4%, 95% CI: -12.5 to 17.3%, P = 0.83) and LBR (35.4 versus 30.3%, absolute difference 5.1%, 95% CI: -9.5 to 19.7%, P = 0.51) per started cycle in recurrent and primary endometrioma were similar. Comparable success rates were also confirmed with logistic regression analysis (OR: 1.14, 95% CI: 0.78-0.57, P = 2.3). Limitations, reasons for caution The retrospective design has inherent limitations. Some women with severely decreased ovarian reserve after primary endometrioma excision may not have pursued further treatment. Wider implications of the findings The management of endometrioma prior to ART is controversial but a different management strategy is not required for recurrent endometriomas. Since recurrent endometriomas do not have a worse impact on ART outcome than primary endometriomas, and repeat surgery has a higher risk for complications, conservative management without surgery can be justified. Study funding/competing interest(s) No funding or competing interests to declare. Trial registration number None.

Day 3 embryo transfer versus day 5 blastocyst transfers: A prospective randomized controlled trial.

Objective:This study aimed to show whether transferring day 5 embryos resulted in higher implantation and pregnancy rates than transferring day 3 embryos in Turkish women undergoing an intracytoplasmic sperm injection (ICSI) cycle.Materials and Methods:A total of 190 women who had ICSI after retrieval of more than four oocytes on the day of fertilization check were randomly assigned to undergo embryo transfer either on day 3 or day 5.Results:Day 3 and day 5 transfers were statistically similar with respect to the age of woman (p=0.107), duration of infertility (p=0.528), cause of infertility (p=0.850), number of collected oocytes (p=0.119), number of metaphase II oocytes (p=0.178), number of fertilized oocytes (p=0.092), and number of transferred embryos (p=0.556). The number of grade 1 embryos was significantly higher in day 5 transfers than in day 3 transfers (p=0.001). Day 3 and day 5 embryo transfers had statistically similar implantation, clinical pregnancy, twinning, and live birth rates (p=0.779, p=0.771, p=0.183, and p=0.649, respectively). The live birth rates in singleton pregnancies conceived after day 3 and day 5 embryo transfers were statistically similar (p=0.594).Conclusion:The efficacy of blastocyst transfer is not inferior to that of embryo transfer on cleavage stage. Performing blastocyst transfer may have benefits because it is associated with acceptable pregnancy rates and morphologic assessment on day 3 has limited predictive value for subsequent embryonic development.

Male chromosomal polymorphisms reduce cumulative live birth rate for IVF couples.

Chromosomal polymorphisms are associated with infertility, but their effects on assisted reproductive outcomes are still quite conflicting, especially after IVF treatment. This study evaluated the role of chromosomal polymorphisms of different genders in IVF pregnancy outcomes. Four hundred and twenty-five infertile couples undergoing IVF treatment were divided into three groups: 214 couples with normal chromosomes (group A, control group), 86 couples with female polymorphisms (group B), and 125 couples with male polymorphisms (group C). The pregnancy outcomes after the first and cumulative transfer cycles were analyzed, and the main outcome measures were live birth rate (LBR) after the first transfer cycle and cumulative LBR after a complete IVF cycle. Comparison of pregnancy outcomes after the first transfer cycle within group A, group B, and group C demonstrated a similar LBR as well as other rates of implantation, clinical pregnancy, early miscarriage, and ongoing pregnancy (P>0.05). However, the analysis of cumulative pregnancy outcomes indicated that compared with group A, group C had a significantly lower LBR per cycle (80.4 vs 68.00%), for a rate ratio of 1.182 (95% CI 1.030 to 1.356, P=0.01) and a significantly higher cumulative early miscarriage rate (EMR) among clinical pregnancies (7.2 vs 14.7%), for a rate ratio of 0.489 (95% CI 0.248 to 0.963, P=0.035). Couples with chromosomal polymorphisms in only male partners have poor pregnancy outcomes after IVF treatment manifesting as high cumulative EMR and low LBR after a complete cycle.

Fresh versus frozen embryo transfers in assisted reproduction.

In general, in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) implies a single fresh and one or more frozen-thawed embryo transfers. Alternatively, the 'freeze-all' strategy implies transfer of frozen-thawed embryos only, with no fresh embryo transfers. In practice, both strategies can vary technically including differences in freezing techniques and timing of transfer of cryopreservation, that is vitrification versus slow freezing, freezing of two pro-nucleate (2pn) versus cleavage-stage embryos versus blastocysts, and transfer of cleavage-stage embryos versus blastocysts.In the freeze-all strategy, embryo transfers are disengaged from ovarian stimulation in the initial treatment cycle. This could avoid a negative effect of ovarian hyperstimulation on the endometrium and thereby improve embryo implantation. It could also reduce the risk of ovarian hyperstimulation syndrome (OHSS) in the ovarian stimulation cycle by avoiding a pregnancy.We compared the benefits and risks of the two treatment strategies. To evaluate the effectiveness and safety of the freeze-all strategy compared to the conventional IVF/ICSI strategy in women undergoing assisted reproductive technology. We searched the Cochrane Gynaecology and Fertility Group Trials Register, the Cochrane Central Register of Studies (CRSO), MEDLINE, Embase, PsycINFO, CINAHL, and two registers of ongoing trials in November 2016 together with reference checking and contact with study authors and experts in the field to identify additional studies. We included randomised clinical trials comparing a freeze-all strategy with a conventional IVF/ICSI strategy which includes fresh transfer of embryos in women undergoing IVF or ICSI treatment. We used standard methodological procedures recommended by Cochrane. The primary review outcomes were cumulative live birth and OHSS. Secondary outcomes included other adverse effects (miscarriage rate). We included four randomised clinical trials analysing a total of 1892 women comparing a freeze-all strategy with a conventional IVF/ICSI strategy. The evidence was of moderate to low quality due to serious risk of bias and (for some outcomes) serious imprecision. Risk of bias was associated with unclear blinding of investigators for preliminary outcomes of the study, unit of analysis error, and absence of adequate study termination rules.There was no clear evidence of a difference in cumulative live birth rate between the freeze-all strategy and the conventional IVF/ICSI strategy (odds ratio (OR) 1.09, 95% confidence interval (CI) 0.91 to 1.31; 4 trials; 1892 women; I2 = 0%; moderate-quality evidence). This suggests that if the cumulative live birth rate is 58% following a conventional IVF/ICSI strategy, the rate following a freeze-all strategy would be between 56% and 65%.The prevalence of OHSS was lower after the freeze-all strategy compared to the conventional IVF/ICSI strategy (OR 0.24, 95% CI 0.15 to 0.38; 2 trials; 1633 women; I2 = 0%; low-quality evidence). This suggests that if the OHSS rate is 7% following a conventional IVF/ICSI strategy, the rate following a freeze-all strategy would be between 1% and 3%.The freeze-all strategy was associated with fewer miscarriages (OR 0.67, 95% CI 0.52 to 0.86; 4 trials; 1892 women; I2 = 0%; low-quality evidence) and a higher rate of pregnancy complications (OR 1.44, 95% CI 1.08 to 1.92; 2 trials; 1633 women; low-quality evidence). There was no difference in multiple pregnancies per woman after the first transfer (OR 1.11, 95% CI 0.85 to 1.44; 2 trials; 1630 women; low-quality evidence), and no data were reported for time to pregnancy. We found moderate-quality evidence showing that one strategy is not superior to the other in terms of cumulative live birth rates. Time to pregnancy was not reported, but it can be assumed to be shorter using a conventional IVF/ICSI strategy in the case of similar cumulative live birth rates, as embryo transfer is delayed in a freeze-all strategy. Low-quality evidence suggests that not performing a fresh transfer lowers the OHSS risk for women at risk of OHSS.

Elective single blastocyst transfer in advanced maternal age

The purpose of this study was toinvestigate reproductive outcomes following elective single blastocyst transfer (eSBT) compared with those of double blastocyst transfer (DBT) in advanced maternal age. This was a retrospective cohort study performed at an academic fertility center. All women aged 40 and over for whom in vitro fertilization (IVF) cycles were performed and in whom embryo culture was extended to the blastocyst stage were reviewed for possible inclusion. Exclusion criteria included the following: women with >3 previous IVF cycles, the use of donor or frozen oocytes, preimplantation genetic diagnosis/preimplantation genetic screening cycles, and cycles in which embryos did not reach the blastocyst stage on day 5. The study included 310 women; 148 were included in the eSBT group and 162 were included in the DBT group. Live birth rate (LBR) was the main outcome. Outcomes were analyzed using logistic regression, controlling for confounders. These confounders were embryo expansion, embryo quality, and the number of previous IVF cycles. The mean age of the whole group was 41±0.91years, and the LBR was 21.6%. The eSBT group and the DBT group achieved similar clinical pregnancy rates (33 vs. 33%) (OR 1.04; 95%CI, 0.62-1.75) and LBRs (20 vs. 22.8%) (OR 1.43; 95% CI, 0.78-2.64). The multiple birth rate was lower in the eSBT group (0 vs. 16%, p=0.02). The subgroup of women who had elective DBT (eDBT) achieved a higher LBR (20 vs. 30.6%) (OR 2.32; 95% CI, 1.16-4.68) and a higher multiple birth rate (0 vs. 22%, p=0.001). Cycles with early blastocyst transfers were associated with lower LBRs compared with cycles with fully expanded blastocyst transfers (11 vs. 24%, p=0.02). The results of this study indicate that eSBT is associated with similar LBRs compared to the entire DBT cohort; however, when supernumerary blastocysts are available for cryopreservation, eDBT is associated with both higher LBRs and a higher number of multiple births. Studies assessing the cumulative LBR in advanced maternal age after single blastocyst transfer and subsequent frozen-thawed blastocyst transfers are needed.

Blastocoele re-expansion time in vitrified-warmed cycles is a strong predictor of clinical pregnancy outcome.

To assess the predictive value of blastocoele re-expansion time in clinical pregnancy outcome in vitrified-warmed cycles. Data on 468 single vitrified-thawed blastocyst transfer cycles (in patients aged <38 years) carried out from January 2012 through December 2012, at the Reproductive Medicine Center, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, were analyzed. Vitrified-warmed blastocysts were divided into three groups according to blastocoele re-expansion time: group A, <1 h; group B, 1-2 h; and group C, >2 h, and the clinical pregnancy outcomes (i.e. live birth rate, miscarriage rate and occurrence of singleton pregnancies) compared between the groups. Significant differences were observed in the implantation/clinical pregnancy rate between groups A, B and C (70.10%, 51.76% and 28.74%, respectively, P < 0.01). There was a significant linear decline in this rate with increasing blastocyst re-expansion time. The rate of miscarriage also tended to increase with increasing blastocyst re-expansion time, but the difference was not statistically significant (P > 0.05). Of the pregnant patients, no significant difference was observed in the rates of monozygotic twins and ectopic pregnancy between the three groups. For the newborns, similar live birth, low-birthweight and premature delivery rates were observed between the groups. Timing of blastocoele re-expansion in vitrified-warmed cycles is a strong predictor of clinical pregnancy outcome. The faster the re-expansion of the blastocoele, the higher the developmental potential of the blastocysts.

Effect of pretreatment with oral contraceptives and progestins on IVF outcomes in women with polycystic ovary syndrome.

Do oral contraceptives (OCs) and progestins impact live birth rate ofIVF when used for cycle scheduling in women with polycystic ovary syndrome (PCOS)? OCs used for scheduling IVF cycle were associated with lowered rates of pregnancy and live birth after fresh embryo transfer, whereas progestins used for this purpose yield higher rates of pregnancy and live birth than OCs. Due to oligo-menorrhea in PCOS, OCs and progestin are extensively used to schedule the start of an IVF cycle in women with PCOS. Little is known about the effect of such pretreatments on outcomes, especially, the rate of live birth. This was a nested cohort study and secondary analysis of a multicenter randomized trial, which was designed to compare live birth rate after fresh embryo transfer vs frozen embryo transfer (FET) in women with PCOS (Frefro-PCOS). A total of 1508 women were enrolled from 14 centers between June 2013 and May 2014. At the discretion of local investigators, subjects were instructed to wait for spontaneous menses (Control group, n = 323), or were prescribed progestins (P group, n = 283) or OCs (OCs group, n = 902) to induce menstruation prior to the start of ovarian stimulation. GnRH antagonist protocol was initiated at Day 2 or 3 of induced or spontaneous menses cycle. The rates of pregnancy, pregnancy loss and live birth after either fresh embryo transfer or FET were compared among these three groups. With fresh embryo transfer, women with OC-induced menses had lower rates of clinical pregnancy (48.8% vs 63.6%, relative rate (RR): 0.77, 95% CI: 0.66-0.89) and live birth (36.1% vs 48.1%, RR: 0.75, 95% CI: 0.61-0.92) than women with spontaneous menses. With freeze-all and deferred FET, women with OC-induced menses had a similar pregnancy rate but a higher pregnancy loss rate (27.7% vs 13.0%, RR: 2.13, 95% CI: 1.28-3.52) after FET than women with spontaneous menses. The live birth rate after FET in women with OC-induced menses, progestin-induced menses and spontaneous menses was 49.4%, 50.7% and 60.2%, respectively (P = 0.06). Progestin-induced menses was associated with similar rates of pregnancy, pregnancy loss and live birth after transfer of either fresh or frozen embryos compared with spontaneous menses. Multivariate logistic regression analysis showed that OCs used for menses induction was associated with lower rate of live birth. The methods for menses induction were not assigned randomly, thus selection bias was highly likely because of the study design and significant differences that were observed in the baseline characteristics of the women in the different groups. The mean BMI in this study population was relatively normal; the applicability of this result to obese PCOS women needs to be evaluated in further study. Our results suggest that either waiting for a spontaneous menses or using progestin is a better option than using OCs to induce menses in women with PCOS prior to ovarian stimulation using GnRH antagonist protocol for IVF. Further randomized controlled studies are needed to confirm our findings. This study was funded by National Basic Research Program of China (973 Program) (2012CB944700), the State Key Program of National Natural Science Foundation of China (81430029), National Natural Science Foundation of China (81471428) and Thousand Talents Program (Drs Legro and Zhang H). Dr Legro reports receiving consulting fees from Euroscreen, Kindex, Bayer and Millendo Pharmaceuticals and research funding from Ferring. Others report no disclosures. Frefro-PCOS was registered at Clinicaltrials.gov: NCT01841528.

Direct Unequal Cleavages: Embryo Developmental Competence, Genetic Constitution and Clinical Outcome.

ObjectiveTo investigate the prevalence, developmental potential, chromosomal constitution and clinical outcome of embryos with direct unequal cleavages (DUC).DesignA retrospective observational study.SettingAcademic Institution.Participant21,261 embryos from 3,155 cycles cultured in EmbryoScope®.ResultsThe total incidence of DUCs per embryo occupying the first three cleavages were 26.1%. Depending of the cell stage, DUC rate was 9.8% at first cleavage (DUC-1), 9.1% at second cleavage (DUC-2), and 3.7% at third cleavage (DUC-3) with 3.6% of embryos exhibiting multiple DUCs (DUC-Plus). The occurrence of DUCs was not correlated with female gamete age or source. The incidence of DUC-1 was significantly higher in embryos fertilized by epididymal and testicular sperm (13.6% and 11.4%, respectively) compared to ejaculated sperm (9.1%, all p<0.05). The total incidences of DUCs were strongly correlated with the onset of blastomere multinucleation (MNB) during the first three divisions. In MNB embryos, DUCs incidence are two to three times more likely to develop when compared to non-MNB embryos (OR = 3.11, 95% CI [2.64, 3.67] at 1-cell stage, OR = 2.64, 95% CI [2.39, 2.91] at 2-cell stage and OR = 2.51, 95% CI [1.84, 3.43] at 4-cell stage). The blastocyst formation rates gradually decreased from 61.0% in non-DUC to 40.2% in DUC-3, 18.8% in DUC-2, 8.2% in DUC-1 and 5.6% in multiple DUC embryos (DUC-Plus). The known implantation rates (FH) for day 3 (D3) transfers were 12.42% (n = 3172) in Non-DUC embryos, 6.3% (n = 127) in DUC-3, and 2.7% (n = 260) in DUC-2 embryos. No live births resulted from either DUC-1 (n = 225) or DUC-Plus (n = 100) embryo transfers. For blastocyst transfers, lower implantation rates (33.3%) but similar live birth (LB) rates (40%) were observed if DUC blastocysts were transferred. Comparatively rates in Non-DUC blastocyst were 45.2% and 34.8%, respectively. The euploid rate gradually increased from DUC-1, -2, -3 to Non-DUC (13.3%, 19.5%, 33.3%, 45.6%, p<0.001) for D3 biopsied embryos. Interestingly, the trend of decreased euploidy disappeared in DUC D5/6 biopsied embryos and similar rates were exemplified in DUC (D5 56.3%, D6 35.6%) vs. non-DUC (D5 51.4%, D6 33.8%) embryos.ConclusionBlastocyst formation, implantation potential and euploid rate were significantly reduced in DUC embryos. DUC embryos should be deselected for D3 transfers, but should be culture to blastocyst stage for possible ET.

Clomiphene Citrate versus Letrozole for Ovarian Stimulation in Therapeutic Donor Sperm Insemination

Aim: To compare clomiphene citrate (CC) and letrozole for ovarian stimulation (OS) in therapeutic donor sperm insemination (TDI) cycles. Methods: Retrospective cohort study between January 2011 and June 2014 at a University-affiliated private IVF clinic in Montreal, Canada. 257 normo-ovulatory women ≤40 years of age with no history of infertility undergoing 590 TDI cycles in the absence of a male partner (single women and same-sex couples) or azoospermia were included. Patients received 100 mg CC daily (145 women, 321 cycles) or letrozole 5 mg daily (112 women, 269 cycles), from days 3 to 7. Only the first 3 cycles were included per patient. Our main outcome measure was cumulative live birth rates (LBR). Results: Baseline characteristics were comparable between the 2 groups. There were no differences in LBR per cycle (16.5% (53/321) vs. 11.5% (31/269), p = 0.08) and cumulative LBR (36.6% (53/145) vs. 27.7% (31/112), p = 0.13), between CC and letrozole, respectively. Multiple pregnancy rate (11.6% (8/69) vs. 8.7% (4/46), p = 0.6) and miscarriage rate (21.7 vs. 21.7%, p = 1) were also comparable between CC and letrozole, respectively. Conclusion: In normo-ovulatory women undergoing TDI, OS with CC or letrozole resulted in similar live birth and twin pregnancy rates.