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Live birth rates and perinatal outcomes when all embryos are frozen compared with conventional fresh and frozen embryo transfer: a cohort study of 337,148 in vitro fertilisation cycles.

ABSTRACT: BACKGROUND:It is not known whether segmentation of an in vitro fertilisation (IVF) cycle, with freezing of all embryos prior to transfer, increases the chance of a live birth after all embryos are transferred. METHODS:In a prospective study of UK Human Fertilisation and Embryology Authority data, we investigated the impact of segmentation, compared with initial fresh embryo followed by frozen embryo transfers, on live birth rate and perinatal outcomes. We used generalised linear models to assess the effect of segmentation in the whole cohort, with additional analyses within women who had experienced both segmentation and non-segmentation. We compared rates of live birth, low birthweight (LBW ?4?kg), small for gestational age (SGA ?90th centile) for a given ovarian stimulation cycle accounting for all embryo transfers. RESULTS:We assessed 202,968 women undergoing 337,148 ovarian stimulation cycles and 399,896 embryo transfer procedures. Live birth rates were similar in unadjusted analyses for segmented and non-segmented cycles (rate ratio 1.05, 95% CI 1.02-1.08) but lower in segmented cycles when adjusted for age, cycle number, cause of infertility, and ovarian response (rate ratio 0.80, 95% CI 0.78-0.83). Segmented cycles were associated with increased risk of macrosomia (adjusted risk ratio 1.72, 95% CI 1.55-1.92) and LGA (1.51, 1.38-1.66) but lower risk of LBW (0.71, 0.65-0.78) and SGA (0.64, 0.56-0.72). With adjustment for blastocyst/cleavage-stage embryo transfer in those with data on this (329,621?cycles), results were not notably changed. Similar results were observed comparing segmented to non-segmented within 3261 women who had both and when analyses were repeated excluding multiple embryo cycles and multiple pregnancies. When analyses were restricted to women with a single embryo transfer, the transfer of a frozen-thawed embryo in a segmented cycles was no longer associated with a lower risk of LBW (0.97, 0.71-1.33) or SGA (0.84, 0.61-1.15), but the risk of macrosomia (1.74, 1.39-2.20) and LGA (1.49, 1.20-1.86) persisted. When the analyses for perinatal outcomes were further restricted to solely frozen embryo transfers, there was no strong statistical evidence for associations. CONCLUSIONS:Widespread application of segmentation and freezing of all embryos to unselected patient populations may be associated with lower cumulative live birth rates and should be restricted to those with a clinical indication.

SUBMITTER: Smith ADAC

PROVIDER: S-EPMC6852977 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Live birth rates and perinatal outcomes when all embryos are frozen compared with conventional fresh and frozen embryo transfer: a cohort study of 337,148 in vitro fertilisation cycles.

Smith Andrew D A C ADAC Tilling Kate K Lawlor Deborah A DA Nelson Scott M SM

BMC medicine 20191113 1

<h4>Background</h4>It is not known whether segmentation of an in vitro fertilisation (IVF) cycle, with freezing of all embryos prior to transfer, increases the chance of a live birth after all embryos are transferred.<h4>Methods</h4>In a prospective study of UK Human Fertilisation and Embryology Authority data, we investigated the impact of segmentation, compared with initial fresh embryo followed by frozen embryo transfers, on live birth rate and perinatal outcomes. We used generalised linear m ...[more]

PMID: 31718643

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Project description:Study questionDoes supplementation with vaginal tablets of progesterone after frozen-thawed embryo transfer in natural cycles improve the live birth rate?Summary answerSupplementation with vaginal tablets of progesterone after frozen-thawed embryo transfer in natural cycles significantly improves the number of live births.What is known alreadyProgesterone supplementation during luteal phase and early pregnancy may improve the number of live births after frozen-thawed embryo transfer. However, due to the limited number of previous studies, being mainly retrospective, evidence is still limited.Study design, size, durationThis is a prospective randomized controlled trial, performed at two university clinics. In total, 500 subjects were randomized with a 1:1 allocation into two groups, during the period February 2013 to March 2018. Randomization was performed after a frozen embryo transfer in a natural cycle by use of opaque sealed envelopes. The primary outcome was live birth rate; secondary outcomes were pregnancy, biochemical pregnancy, clinical pregnancy and miscarriage rate, and if there was a possible association between the serum progesterone concentration on the day of embryo transfer and live birth rate.Participants/materials, setting, methodsWomen, receiving embryo transfer in natural cycles participated in the study. The embryos were frozen on Day 2, 3, 5 or 6. In total, 672 women having regular menstrual cycles were invited to participate in the study; of those, 500 agreed to participate and 488 were finally included in the study. Half of the study subjects received progesterone supplementation with progesterone vaginal tablets, 100 mg twice daily, starting from the day of embryo transfer. The other half of the subjects were not given any treatment. Blood samples for serum progesterone measurements were collected from all subjects on the day of embryo transfer.Main results and the role of chanceThere were no differences in background characteristics between the study groups. In the progesterone supplemented group, 83 of 243 patients (34.2%) had a live birth, compared to 59 of 245 patients (24.1%) in the control group (odds ratio 1.635, 95% CI 1.102-2.428, P = 0.017*). The number of pregnancies was 104 of 243 (42.8%) and 83 of 245 (33.9%), respectively (odds ratio 1.465, 95% CI 1.012-2.108, P = 0.049*) and the number of clinical pregnancies was 91 of 243 (37.4%) and 70 of 245 (28.6%), respectively (odds ratio 1.497, 95% CI 1.024-2.188, P = 0.043*). There were no significant differences in biochemical pregnancy rate or miscarriage rate. There was no correlation between outcome and serum progesterone concentration.Limitations, reasons for cautionThe study was not blinded because placebo tablets were not available. Supplementation started on embryo transfer day, regardless of the age of the embryos, which resulted in a shorter supplementation time for Day 5/6 embryos compared to Day 2/3 embryos.Wider implications of the findingsSupplementation with progesterone in natural cycles improved the number of live births after frozen-thawed embryo transfer and should therefore be considered for introduction in clinical routine.Study funding/competing interest(s)The study was funded by Uppsala University, the Uppsala-Family Planning Foundation, and Ferring Pharmaceuticals AB, Malmö, Sweden. The authors have no personal conflicting interests to declare.Trial registration numberNL4152.Trial registration date5 December 2013.Date of first patient’s enrolment18 February 2013.

Project description:BackgroundUterine adenomyosis is a benign disease, common among women in their 40 and 50 s, characterised by ectopic endometrial tissue in the uterine myometrial layer. Adenomyosis causes infertility and has a negative effect on the outcomes of in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) embryo transfer (ET) cycles. It has also been reported to have different characteristics depending on the adenomyotic lesion localisation. The effect of its localisation on IVF/ICSI-ET outcomes is unclear. This study aimed to investigate whether adenomyotic lesion localisation, assessed using magnetic resonance imaging (MRI), was associated with outcomes of IVF/ICSI-ET cycles.MethodsThis multicentre, joint, retrospective cohort study analysed the medical records of 67 infertile patients with adenomyosis who underwent IVF/ICSI with fresh and frozen-thawed ET at five participating facilities from January 2012 to December 2016 and for whom MRI data were available. Fifteen patients were excluded; therefore, the MRI data of 52 patients were evaluated by two radiologists. We assessed the localisation of and classified adenomyotic lesions into advanced (invades the full thickness of the uterine myometrium), extrinsic (localised on the serosal side), and intrinsic (localised on the endometrial side) subtypes.ResultsThere were 40 advanced, nine extrinsic, and three intrinsic cases, and the outcomes of 100, 27, and nine ET cycles, respectively, were analysed. Pregnancy loss/clinical pregnancy and live birth rates of the advanced, extrinsic, and intrinsic groups were 64 % (16/25) and 9 % (9/100), 33.3 % (3/9) and 22.2 % (6/27), and 50 % (1/2) and 11.1 % (1/9), respectively. A logistic regression analysis adjusted for age, prior miscarriage, and body mass index showed that the extrinsic group had fewer pregnancy losses (odds ratio 0.06; 95 % confidence interval [CI]: 0.00-0.54, p = 0.026) and more live births (odds ratio 6.05; 95 % CI: 1.41-29.65, p = 0.018) than the advanced group.ConclusionsAdenomyotic lesions exert different effects on IVF/ICSI-ET outcomes. Thus, MRI assessments of adenomyosis in infertile patients are beneficial. Establishment of treatment plans based on adenomyotic lesion localisation should be considered.

Dataset Information

Live birth rates and perinatal outcomes when all embryos are frozen compared with conventional fresh and frozen embryo transfer: a cohort study of 337,148 in vitro fertilisation cycles.

Publications

Live birth rates and perinatal outcomes when all embryos are frozen compared with conventional fresh and frozen embryo transfer: a cohort study of 337,148 in vitro fertilisation cycles.

Similar Datasets

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