Protocoles de replacement d’embryons congelés : le cycle spontané donne-t-il de bons résultats ?

ObjectiveFrozen embryos’ transfer optimize the pregnancy rates per retrieval. In France, 60% of transfer cycles occur in stimulated cycles. The aim of this study was to evaluate the outcomes of frozen embryo transfers in spontaneous, substituted and stimulated cycle.Patients and methodsThis retrospective study includes patients who are 18–43 years old and had a frozen embryo transfer between 1st January 2008 and 31st December 2008. Three transfer protocols have been used: the spontaneous cycle (group 1), substituted cycle (group 2), and stimulated cycle (group 3). The characteristics of couples, embryonic parameters and data transfer cycles, and their outcomes were evaluated.Result(s)Among the 333 patients, 132 were included in the first group, 24 in the second group and 177 in the third group. After checking the homogeneity of the three groups, we found pregnancy rates (respectively 20.49 vs 13.04% and 11.32%, P = 0.0348), and deliveries (respectively 13.93 vs 8,7 and 6.29%, P = 0.0314), significantly higher in spontaneous cycles.Discussion and conclusionCurrently there is no consensus on the best technique for endometrial preparation for frozen embryo transfer. Our results support transfers in spontaneous cycle for normo-ovulating patients. Natural cycles can achieve good pregnancy rates while minimizing the costs and side effects.     

Risk factors for clinical pregnancy loss after IVF in women with PCOS

Research questionWhich factors are associated with the risk of clinical pregnancy loss in women with polycystic ovary syndrome (PCOS) undergoing IVF?DesignCase–control study nested in a multicentre randomized trial comparing live birth rates between fresh and frozen embryo transfer in women with PCOS. Women with the outcome of clinical pregnancy loss were selected as the case group, those with live birth as the control group. Parameters before IVF treatment and variables during ovarian stimulation and embryo transfer were compared.ResultsWomen with clinical pregnancy loss had higher maternal body mass index (BMI, P = 0.010), anti-Müllerian hormone (AMH, P = 0.032), 2-h glucose concentration after 75 g oral glucose tolerance test (OGTT, P = 0.025), and a higher proportion of fresh embryo transfers (P = 0.001). There were significant interactions between the types of transfer and antral follicle count (AFC, P = 0.013), 2-h glucose concentration after OGTT (P = 0.024) on clinical pregnancy loss in PCOS, indicating that these factors may have different effects on pregnancy loss after fresh versus frozen embryo transfer. When the multivariable logistic regression analysis was stratified by the fresh or frozen embryo transfer, AFC (adjusted odds ratio [aOR] 1.03, 95% confidence interval [CI] 1.01–1.05) was a risk factor for clinical pregnancy loss after fresh embryo transfer, while 2-hour glucose concentration after OGTT (aOR 1.13, 95% CI 1.01–1.25) was associated with clinical pregnancy loss in frozen embryo transfer (FET) cycles.ConclusionsIn women with PCOS, fresh embryo transfer, higher BMI, AFC and 2-h glucose concentration after OGTT were risk factors for clinical pregnancy loss. FET may be a better choice to decrease the risk of clinical pregnancy loss, especially for those with higher AFC. During FET, 2-h glucose after OGTT appears to be associated with clinical pregnancy loss and warrants close monitoring.     

Risk of miscarriage in women conceiving after medically assisted reproduction with an ultrasound-verified viable pregnancy at 6–8 weeks’ gestation

Research questionWhat is the risk of miscarriage after a viable fetus verified on ultrasound at 6–8 weeks’ gestation among women who conceive with medically assisted reproduction (MAR), stratified by type of fertility treatment?DesignA nationwide register-based cohort study of women identified in the Danish ART-Registry with a viable singleton pregnancy at 6–8 weeks’ gestation between 2007 and 2010 (n = 10,011). Women were identified from The Danish Fetal Medicine Database (DFMD), which holds information on early (between 6–8 and 11–14 weeks) and late (between 11–14 and 22 weeks) miscarriages. The late miscarriage rate was compared with a control group of naturally conceived pregnancies with a viable fetus at 11–14 weeks’ gestation from 2008 to 2010, identified in the DFMD (n = 146,932).ResultsIn the MAR1 cohort, the overall miscarriage rate was 11.8% (1091/9261) after an ultrasound verified viable pregnancy at 6–8 weeks’ gestation. Most miscarriages occurred before the 11–14-week scan (1035/1091 [94.9%]). The early miscarriage rate was slightly higher in women who conceived with frozen embryo transfer compared with intrauterine insemination (IUI), corresponding to an adjusted OR of 1.31 (1.02 to 1.68). We found no significant risk associated with IVF and intracytoplasmic sperm injection compared with IUI pregnancies. The late miscarriage rate was 0.8% in women conceiving with MAR and 0.6% among controls (P = 0.013).ConclusionsAfter adjustment for maternal characteristics, none of the fertility treatment types were associated with an increased risk of miscarriage compared with naturally conceiving women.     

Predictive value of serum kisspeptin concentration at 14 and 21 days after frozen–thawed embryo transfer

Research questionCan serum kisspeptin levels 14 and 21 days after frozen–thawed embryo transfer predict the early pregnancy outcome of patients?DesignProspective study, with 133 patients undergoing frozen–thawed embryo transfer. Patients were divided into non-pregnant group and pregnant group (including biochemical pregnancy, singleton pregnancy, miscarriage and twin groups).ResultsSerum kisspeptin levels on day 21 were significantly higher than day 14 in singleton pregnancy, miscarriage and twin groups (all P < 0.0001), but not in the biochemical pregnancy group. Similarly, serum human chorionic gonadotrophin (HCG) levels were higher on day 21 compared with day 14 except for the biochemical pregnancy group. Compared with the twin group (296.9 pg/ml), the other four groups showed significantly higher serum kisspeptin levels on day 14 (non-pregnant 548.9, biochemical pregnancy 440.4, miscarriage 434.9, singleton pregnancy group 420.9 pg/ml, P < 0.01, P = 0.016, P = 0.034, P = 0.036, respectively). The miscarriage (762.2 pg/ml), singleton pregnancy (730.8 pg/ml) and twin groups (826.3 pg/ml) had significantly higher kisspeptin levels than the biochemical pregnancy group (397.3 pg/ml) on day 21 (P < 0.001, P < 0.01, P < 0.001, respectively). Serum kisspeptin levels on day 14 were negatively correlated with embryo implantation rate (P = 0.035, R² = –0.880). Serum kisspeptin levels on day 21 have a poor predictive value of miscarriage compared with serum HCG levels (area under the curve = 0.53 and 0.78, respectively).ConclusionsSerum kisspeptin levels on day 14 are negatively correlated with embryo implantation rate. Serum kisspeptin levels on day 21 have a poor predictive value of miscarriage.     

Does blastocyst mitochondrial DNA content affect miscarriage rate in patients undergoing single euploid frozen embryo transfer?

PurposeTo determine whether the blastocyst mitochondrial DNA (mtDNA) content is related to the miscarriage rate in patients undergoing single euploid frozen embryo transfer (SEFET).MethodsA total of 355 single euploid frozen embryo transfer cycles were studied retrospectively between April 2017 and December 2018. A trophectoderm biopsy was performed on day 5/6 blastocysts. Post next-generation sequencing (NGS), the mtDNA content was calculated as the ratio of mitochondrial DNA over nuclear DNA, and the association between blastocyst mtDNA content and miscarriage rate was evaluated.Result(s)Three hundred fifty-five euploid blastocysts were selected for SEFET in 314 patients with an average age of 33.7 ± 5.6 years; 255 were biopsied on day 5 (71.8%) and 100 on day 6 (28.2%). Frozen embryo transfer (FET) was performed either in a hormone replacement therapy (HRT) cycle (71.8%; n = 255) or in a natural cycle (NC) (28.2%; n = 100). A pregnancy rate of 66.2% (235/355) was obtained with clinical pregnancy and miscarriage rates of 52.4% (n = 186) and 5.6% (n = 20), respectively. There was no significant difference neither between the blastocyst mtDNA content of pregnant and nonpregnant patients (27.7 ± 9.2 vs. 29.4 ± 8.6, P = 0.095) nor between patients with a clinical pregnancy and miscarriage (30.5 ± 9.3 vs. 27.3 ± 9.2, P = 0.136). Multivariate logistic regression analysis showed the same nonsignificant relationship, except for the miscarriage rate and BMI (OR 1.149, 95% CI 1.03–1.28; P = 0.012).Conclusion(s)Mitochondrial DNA content is unable to predict the miscarriage of implanted human euploid blastocysts.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10815-020-02050-8.     

Weekly intramuscular progesterone for luteal phase support in women receiving oocyte donation is associated with a decreased miscarriage rate

Research questionTo determine whether adding intramuscular to vaginal administration of progesterone reduces miscarriage rates compared with those of vaginal administration alone for luteal phase support in women receiving oocyte donation and to determine the best time to introduce intramuscular progesterone.DesignRetrospective analysis of miscarriage rates in women receiving oocyte donation. Recipients underwent endometrial preparation by hormone replacement treatment. Vaginal progesterone alone or associated with intramuscular progesterone was used for luteal support.ResultsThis study analysed 186 oocyte donation cycles from January 2016 to May 2018 with embryo transfer on Day 2 or 3 and vaginal progesterone administration: 106 embryo transfer cycles with vaginal progesterone alone, 29 with weekly intramuscular progesterone added once the human chorionic gonadotrophin (HCG) assay was positive, and 51 with weekly intramuscular progesterone added the evening of embryo transfer. The rates of positive HCG assays, biochemical pregnancies and clinical pregnancies did not differ between the treatment groups. The miscarriage rate was significantly lower when intramuscular progesterone began the evening of embryo transfer than with vaginal administration alone (16.7% versus 47.0%, respectively; P = 0.049 after Bonferroni correction). The live birth rate was higher when intramuscular progesterone began the evening of embryo transfer than with vaginal administration alone (37.3% versus 16.0%, respectively; P = 0.009 after Bonferroni correction).ConclusionsAdding intramuscular to vaginal progesterone administration appears to decrease the miscarriage rate and increase the live birth rate in oocyte donations. The initiation of intramuscular progesterone is most beneficial when it is introduced the evening of embryo transfer.     

Impact of paternal age on IVF and pregnancy outcomes with only normal sperm parameters

ObjectivePrevious reports on advanced paternal age effects on assisted reproductive technology (ART) vary considerably and those on frozen–thawed embryo transfer (FET) are rare. We investigated whether paternal age affects in vitro fertilisation (IVF) and FET pregnancy outcomes.Materials and methods1657 IVF cycles performed from January 2014 to May 2018 were retrospectively investigated excluding cases of poor semen parameters. Paternal and maternal ages were categorised into groups, namely, <35, 35–39 and ≥ 40 years, to compare normal fertilisation (2 PN (pronuclei)) and high-quality blastocyst rates. Furthermore, 741 FET cycles were investigated and pregnancy, live birth and miscarriage rates were compared.ResultsFor the maternal age group (35–39), the 2 PN rate was significantly higher with paternal age group of <35 than groups of 35–39 and ≥ 40 (median%, <35 vs. 35–39 vs. ≥40 = 100.0 vs. 71.4 vs. 77.7; P = 0.005). The miscarriage rate was significantly higher with paternal age group of ≥40 than that of <35 and 35–39 when maternal age was <35 (median %, <35 vs. 35–39 vs. ≥40 = 13.1 vs. 7.8 vs. 33.3; P = 0.038).ConclusionOur findings show that when maternal age was <35, advanced paternal age reduces the normal fertilisation rate and increases the FET miscarriage rate when maternal age was 35–39.     

Sperm DNA fragmentation is a novel biomarker for early pregnancy loss

Research questionSpontaneous pregnancy loss affects 10–15% of couples, with 1–2% suffering recurrent pregnancy loss and 50% of miscarriages remaining unexplained. Male genomic integrity is essential for healthy offspring, meaning sperm DNA quality may be important in maintaining a pregnancy. Does sperm DNA fragmentation measured by alkaline Comet assay act as a biomarker for early pregnancy loss?DesignSperm DNA fragmentation was measured by alkaline Comet test in 76 fertile donors and 217 men whose partners had recently experienced miscarriage. Couples were divided into five groups for analysis: one miscarriage after spontaneous conception; two or more miscarriages after spontaneous conception; one miscarriage after fertility treatment; two or more miscarriages after fertility treatment and biochemical pregnancy.ResultsReceiver operator characteristic curve analysis was used to determine ability of the average Comet score (ACS), low Comet score (LCS) and high Comet score (HCS) to diagnose miscarriage and develop clinical thresholds comparing men whose partners have miscarried with men with recently proven fertility. Male partners of women who had miscarried had higher sperm DNA damage (ACS 33.32 ± 0.57%) than fertile men (ACS 14.87 ± 0.66%; P < 0.001). Average Comet score, HCS and LCS all have promise as being highly predictive of sporadic and recurrent miscarriage using clinical thresholds from comparisons with fertile men's spermatozoa: receiver operating characteristic curve AUC for ACS ≥26%, 0.965; LCS ≤70%, 0.969; HCS ≥2%, 0.883; P <0.0001.ConclusionsSperm DNA damage measured by the alkaline Comet has promise as a robust biomarker for sporadic and recurrent miscarriage after spontaneous or assisted conception, and may provide novel diagnoses and guidance for future fertility pathways.     

Retrospective Review of Reproductive Outcomes Comparing Vaginal Progesterone to Intramuscular Progesterone as Luteal Support in Frozen Embryo Transfer Cycles

ObjectiveRecent literature suggests that progesterone in oil (PIO) is superior to vaginal progesterone (VP; Prometrium) for endometrial preparation in frozen embryo transfer cycles (FET), improving the live birth rate and reducing the rate of miscarriage. PIO has disadvantages including cost, pain, and stress of administration. The objective of this study was to evaluate whether VP is non-inferior to PIO for medicated FET cycles.MethodsWe conducted a retrospective analysis comparing pregnancy, miscarriage, and live birth rates for PIO versus VP for medicated FET cycles, from 2017 to 2020 at a single fertility clinic. A total of 745 participants were included in the study; 438 received VP, and 307 received PIO. Univariate and multivariate binary and ordinal logistic regression analyses were performed to compare the rates of pregnancy, miscarriage, and live birth between VP and PIO.ResultsOur data demonstrated no difference between PIO and VP with respect to the rates of pregnancy (51% vs. 53%), miscarriage (20% vs. 18%), or live birth (31% vs. 34%) (all P > 0.05). For participants taking PIO, the odds of pregnancy were 0.93 [95% CI (0.70, 1.25), P = 0.65] that of participants on VP.ConclusionIn our single-centre experience, VP was non-inferior to PIO for endometrial preparation in FET cycles.     

Three-dimensional ultrasound diagnosis of T-shaped uterus is associated with adverse pregnancy outcomes after embryo transfer

Research questionIs T-shaped uterine cavity morphology associated with adverse pregnancy outcomes after transfer of a single thawed euploid blastocyst?DesignIn this secondary analysis of a prospective cohort study, 648 patients with three-dimensional ultrasound (3D-US) data obtained on the day before embryo transfer were categorized into three groups according to uterine cavity morphology: normal (n = 472), intermediate (n = 166) and T-shaped (n = 10). Quantitative uterine cavity dimensions were used to evaluate uterine cavity morphology. Pregnancy outcomes, including live birth, clinical miscarriage and ectopic pregnancy, were compared among the groups.ResultsThe prevalence of a T-shaped uterus in this cohort was 1.5%. Uterine cavity morphology was strongly associated with the ratio of interostial distance and isthmic diameter (P < 0.01). Live birth rates were 66.5% for normal, 65.7% for intermediate and 40.0% for T-shaped cavity morphology. Women with a T-shaped uterus had an increased risk of clinical miscarriage (40.0% versus 7.0% for normal and 9.0% for intermediate cavity morphology, P < 0.01) and ectopic pregnancy (10.0% versus 1.1% for normal and 1.9% for intermediate cavity morphology, P = 0.05). When evaluating interostial distance and isthmic diameter ratio to determine pregnancy outcomes, a cut-off value of 2 was noted to have weak predictive value for live birth, but not clinical miscarriage or ectopic pregnancy.ConclusionsT-shaped uterine cavity morphology is associated with adverse pregnancy outcomes after transfer of a single thawed euploid blastocyst. Given the low prevalence of this condition, quantifying the magnitude of risk will require a larger cohort of patients.     

The Role of Serum Testosterone in Early Pregnancy Outcome: A Comparison in Women With and Without Polycystic Ovary Syndrome

ObjectiveHyperandrogenic conditions in women are associated with increased rates of miscarriage. However, the specific role of maternal testosterone in early pregnancy and its association with pregnancy outcome is unknown. The purpose of this study was to compare serum testosterone levels during early pregnancy in women with and without polycystic ovary syndrome (PCOS) who either had successful pregnancies or miscarried.MethodWe collected serum samples from women attending a university-based fertility centre at the time of their first positive serum beta human chorionic gonadotropin pregnancy test. The samples were subsequently assayed for total testosterone level. We used logistical regression modelling to control for PCOS diagnosis, BMI, and age.ResultsTotal testosterone levels were available for 346 pregnancies, including 286 successful pregnancies and 78 first trimester miscarriages. We found no difference in total testosterone levels between women who subsequently had an ongoing pregnancy (mean concentration 3.6 ± 2.6 nmol/L) and women with a miscarriage (mean 3.6 ± 2.4 nmol/L). Using the Rotterdam criteria to identify women with PCOS, we also found no differences in serum testosterone between women who had ongoing pregnancies or miscarriages, either with PCOS (P = 0.176) or without PCOS (P = 0.561).ConclusionsOur findings show that early pregnancy testosterone levels do not predict pregnancy outcome, and they call into question the role of testosterone in causing miscarriage in populations of women with PCOS. Further research is needed to elucidate the normal progression of testosterone levels during pregnancy and to investigate further the relationship between PCOS and miscarriage.     

Influence of cleavage-stage embryo quality on the in-vitro fertilization outcome after single embryo transfer in fresh cycles

ObjectiveEmbryo quality is crucial for determining the outcome of embryo implantation. This study aimed to assess the impact of embryo quality on the outcome of in vitro fertilization/single-embryo transfer (IVF-SET).Materials and methodsThis retrospective study included 2531 fresh IVF-SET cycles, including 277 poor-quality and 2254 top-quality embryos. The clinical pregnancy rate, miscarriage rate, live birth, implantation rate, pregnancy outcome and complication were analyzed and compared. Risk factors associated with miscarriage rate and pregnancy complication were identified using logistics regression analysis.ResultsTop-quality embryos resulted in higher clinical pregnancy rate (30.5% vs. 12.6%, P < 0.001) and live birth rate (23.9% vs. 9.7%, P < 0.001) compared with poor-quality embryos. Logistics regression analysis revealed that embryo quality was not correlated with miscarriage rate (95% CI 0.33–1.89) and pregnancy complications (95% CI 0.12–7.84). Maternal age and body mass index was a risk factor for miscarriage rate (95% CI 1.05–1.22) and pregnancy complication (95% CI 1.01–1.29), respectively.ConclusionClinical miscarriage rate and pregnancy complication were embryo quality independent. Maternal age was the risk factor for miscarriage rate. Embryo quality did not affect miscarriage once a clinical pregnancy is achieved.     

Safety and Assisted Reproductive Technology Outcomes of Hysteroscopic Tubal Microinserts Versus Laparoscopic Proximal Tubal Occlusion or Salpingectomy for Hydrosalpinges Treatment

ObjectiveThis study sought to answer the following question: What are the complications and assisted reproductive technology outcomes among women with hydrosalpinges managed by hysteroscopic microinsert tubal occlusion compared with women with hydrosalpinges managed by laparoscopic proximal tubal occlusion or salpingectomy?MethodsThis was a retrospective cohort study conducted from January 2009 to December 2014 at two academic, tertiary care, in vitro fertilization centres in Toronto, Ontario. All patients (n = 52) who underwent hysteroscopic tubal occlusion for hydrosalpinges were identified. Patients who proceeded with embryo transfer cycles after hysteroscopic microinsert (n = 33) were further age matched to a cohort of patients who underwent embryo transfer after laparoscopic proximal tubal occlusion or salpingectomy (n = 33). Main outcome measures were clinical pregnancy rate per patient and per embryo transfer cycle.ResultsAmong 33 patients, there were 39 fresh and 37 frozen embryo transfer cycles in the hysteroscopic group (group A); among 33 patients in the laparoscopic group (group B), there were 42 fresh and 29 frozen embryo transfer cycles. The cumulative clinical pregnancy rate in group A and group B was similar (66.7% vs. 69.7%, respectively; P = 0.8). The clinical pregnancy rate per embryo transfer cycle was also similar in both groups (28.9% in group A vs. 32.4% in group B; P = 0.6). There were two incidents of ectopic pregnancy in the laparoscopic group and no ectopic pregnancy in the hysteroscopic group. There were three major complications: tubo-ovarian abscess, distal migration of the coil after microinsert placement, and an acute abdomen following the hysteroscopic procedure.ConclusionPregnancy outcomes after hysteroscopic placement of a microinsert for hydrosalpinx management before embryo transfer were comparable to those following laparoscopic proximal tubal occlusion or salpingectomy. However, caution is advised regarding microinsert placement for hydrosalpinges before proceeding with assisted reproductive technology.     

Frozen blastocyst embryo transfer using a supplemented natural cycle protocol has a similar live birth rate compared to a programmed cycle protocol

PurposeThe purpose of this study is to compare outcomes for a supplemented natural cycle with a programmed cycle protocol for frozen blastocyst transfer.MethodsA retrospective analysis was performed of frozen autologous blastocyst transfers, at a single academic fertility center (519 supplemented natural cycles and 106 programmed cycles). Implantation, clinical pregnancy, miscarriage, and live birth and birth weight were compared using Pearson’s Chi-squared test, T-test, or Fisher’s exact test.ResultsThere was no significant difference between natural and programmed frozen embryo transfers with respect to implantation (21.9 vs. 18.1 %), clinical pregnancy (35.5 vs. 29.2 %), and live birth rates (27.7 vs. 23.6 %). Mean birth weights were also similar between natural and programmed cycles for singletons (3354 vs. 3340 g) and twins (2422 vs. 2294 g)ConclusionFrozen blastocyst embryo transfers using supplemented natural or programmed protocols experience similar success rates. Patient preference should be considered in choosing a protocol.     

Lower embryonic loss rates among twin gestations following assisted reproduction

Purpose: To determine whether maternal age and number of transferred embryos influence early pregnancy losses in twin pregnancies compared to singletons following IVF/ICSI.Methods: We compared the pregnancy loss rates in singleton (n = 549) and twin (n = 252) gestations, stratified by maternal age (≤35 and > 35 years) and the number of transferred embryos (1–3 and 4–9).Results: Loss rates of singleton pregnancies were significantly higher than that in twins (OR 3.0, 95% CI 1.9, 4.9), especially among singletons conceived after transfer of 4–9 embryos (OR 5.0, 95% CI 2.2, 11.9). Younger mothers of twins had lower loss rates (OR 0.3, 95% CI 0.1, 0.9).Conclusion: Twins have a significantly reduced spontaneous miscarriage rate compared with singletons following IVF/ICSI. Higher implantation rates per cycle (i.e., development of twins rather than one live embryo) may represent a better capacity of the uterus for early embryonic development.     

Transfers of fresh blastocysts and blastocysts cultured from thawed cleavage embryos are associated with fewer miscarriages

The literature shows an inconsistent relationship between miscarriage and assisted reproduction treatment factors. This study assessed the association between miscarriage and transfer of fresh or thawed embryos at cleavage/blastocyst stages. A population study included 52,874 pregnancies following autologous cycles. The miscarriage rate was compared by groups of transferred embryos (fresh cleavage embryo, fresh blastocyst, thawed cleavage embryo, blastocyst from thawed cleavage embryo, thawed blastocyst), IVF/intracytoplasmic sperm injection procedures, number of embryos transferred and woman's demographics. The overall miscarriage rate was 18.7%. Women aged 35-39 years and ≥40 years had a 51% and 177% increased hazard of miscarriage, respectively, compared with women <35 years. Women with history of miscarriage had 1.22 times hazard of miscarriage compared with those without previous miscarriage. Singleton pregnancies following fresh double-embryo transfer had 1.43 times higher rate of miscarriage than fresh single-embryo transfer. Fresh blastocyst transfer was associated with 8% less hazard of miscarriage than fresh cleavage-embryo transfer. Compared with pregnancies following thawed cleavage-embryo transfers, thawed blastocyst transfers were at 14% higher hazard of miscarriage. This study suggests that a practice model that includes transferring blastocysts and freezing cleavage embryos in fresh cycles would result in better outcomes.     

多胎减胎后单胎分娩与单胎妊娠分娩比较分析

目的探讨体外受精-胚胎移植(IVF-ET)助孕单胎分娩者中,孕早期多胎妊娠自然减胎及手术减胎对围产期母儿结局的影响。方法回顾性分析3 376例行IVF助孕治疗,新鲜或冷冻胚胎移植后单胎分娩者的临床资料,根据孕早期宫内孕囊数分组:A组(多胎妊娠,455例),其中A1组(手术减胎,34例),A2组(自然减胎,421例);B组(单胎妊娠,2 921例);分年龄进行组间临床基本资料,出生低体质量儿率、新生儿畸形率、妊娠期并发症等围产期母婴结局的比较。结果 (1)35岁的患者中,A组比B组不孕时间短、移植胚胎数多和优质胚胎数多;(2)囊胚移植比例、冷冻胚胎移植比例A、B组间均无统计学差异;(3)A1组和A2组出生低体质量儿率、出生极低体质量儿率、胎儿畸形率均显著高于B组(P0.05),但A1、A2组间无统计学差异(P0.05),A2组早产率明显增加,与B组有统计学差异(P0.01)。结论多胎妊娠即使减胎后单胎分娩,其新生儿低体质量及畸形风险仍高于单胎妊娠分娩者,35岁、不孕时间短者,建议选择性单优质胚胎移植,以降低多胎妊娠。     

Risk of small for gestational age is reduced after frozen compared with fresh embryo transfer in endometriosis

Research questionWhat are the perinatal outcomes and especially the risk of small for gestational age (SGA) babies born after frozen versus fresh embryo transfer in mothers affected by endometriosis undergoing treatment with assisted reproductive technology (ART)?DesignA cohort study conducted between November 2012 and October 2017, in which infertile women with endometriosis undergoing ART and achieving singleton pregnancies that lasted beyond 12 weeks of gestation were included. Pregnancies obtained after a frozen embryo transfer (FET) were compared with those obtained after a fresh embryo transfer. A total of 339 pregnant women were included: 112 patients in the fresh embryo transfer group and 227 in the FET group. The main outcome was the rate of SGA. Secondary analyses were performed for adverse pregnancy outcomes and perinatal complications.ResultsOf the included women, 109/112 (97.3%) and 222/227 (97.8%) delivered a live child after at least 24 weeks of gestation in the fresh and in the frozen embryo transfer groups, respectively (P = 0.53). The risk of SGA decreased after a FET compared with a fresh embryo transfer (odds ratio [OR] 0.49 [0.25–0.98], P = 0.04) after multivariable analysis. The mean birthweight and the gestational age at delivery were not significantly different between the two study groups. Other pregnancy and perinatal complications were not statistically different between the two study populations.ConclusionsThe present study of endometriosis-affected women found a significantly lower risk of SGA in patients undergoing frozen, mainly blastocyst, embryo transfer compared with patients undergoing fresh, mainly cleavage stage, embryo transfer.     

Characterization of early pregnancy placental progesterone production by use of dydrogesterone in programmed frozen–thawed embryo transfer cycles

Research questionWhen and how does the gradual transition of the endocrine control of early pregnancy from the corpus luteum to the placenta, termed luteoplacental shift, take place?DesignProspective analysis of serum progesterone levels in pregnancies (n = 88) resulting from programmed frozen–thawed embryo transfer cycles in which ovulation was suppressed and no corpus luteum was present. Dydrogesterone, which does not cross-react with progesterone in immunoassay or spectrometric assay, was used for luteal phase and early pregnancy support. Progesterone, oestradiol and hCG were measured at regular intervals from before pregnancy achievement until +65 to 71 days after embryo transfer by Roche Elecsys electrochemiluminescence immunoassay (Elecsys ECLIA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS).ResultsSerum progesterone remained at baseline levels on first blood analysis +9 to 15 days after embryo transfer and increased only marginally independently from the type of pregnancy up to +16 to 22 days after embryo transfer. From +23 to 29 days after embryo transfer, progesterone increased non-linearly above 1.0 ng/ml and increased further throughout the first trimester with elevated levels in multiples. Oestradiol levels increased in parallel with progesterone; hCG plateaued around +37 to 43 days. Progesterone levels were significant predictors for pregnancy viability from +23 to 29 days after embryo transfer onwards with best accuracy +37 to 43 days after embryo transfer (receiver operator characteristic analysis area under the curve 0.98; 95% CI 0.94 to 1; P = 0.0009).ConclusionsThe onset of substantial progesterone production is the 7th gestational week. Progesterone increase is non-linear, depends on chorionicity and zygosity, and may have predictive potential on the outcome of pregnancies originating from frozen embryo transfer cycles.     

Do Multiple Attempts at Embryo Transfer Affect Clinical Pregnancy Rates?

ObjectiveDuring an in vitro fertilization treatment cycle, having embryos retained in the catheter after embryo transfer is a relatively uncommon and frustrating event. The reported incidence of retained embryos varies between 1% and 8%. It can be difficult to explain this unwanted event to patients. We wished to determine the incidence and the effect on pregnancy rates of having embryos retained in the transfer catheter, followed by immediate completion of transfer.MethodsWe performed a retrospective chart review of all IVF cycles with embryos retained in the transfer catheter, followed by repeat transfer, between October 2009 and March 2012. We reviewed IVF cycles with or without ICSI, and included fresh and frozen embryo transfer cycles. All embryos were transferred on the third day after oocyte retrieval. Transabdominal ultrasound was used for guidance during the embryo transfer.ResultsA total of 49 IVF treatment cycles with retained embryos that required re-transfer were identified. This represented 7.5% (49/652) of all IVF cycles with embryo transfer during that period. The clinical pregnancy rate in the repeat transfer group was 30.6% (15/49). The clinical pregnancy rate in all cycles in the same time period was 34.8% (227/652). These rates were not significantly different (P = 0.521).ConclusionHaving to re-transfer embryos retained in the transfer catheter does not have any significant effect on clinical pregnancy rates during IVF treatment cycles.