scholarly journals A Comparison of the Miscarriage and Live Birth Rate for Frozen Embryo Transfer According to Two Endometrial Preparations: Natural or Primed with Estrogens

2019 ◽  
Vol 01 (01) ◽  
pp. 43-49
Author(s):  
S. Mubarak ◽  
S. Acharyya ◽  
V. Viardot-Foucault ◽  
H. H. Tan ◽  
J. W. L. Phoon

Objective The primary objective is to compare miscarriage rates in frozen-thawed embryo transfer (FET) cycles, according to the endometrial preparation used either artificial through the administration of exogenous estrogen and progesterone or natural without any treatment, during a spontaneous ovulatory cycle. The secondary objective is to compare the live birth rates between the two endometrial preparations. Study design This is a retrospective study done at KK Women’s and Children’s Hospital Singapore. We included women who underwent FET cycles either with hormone replacement treatment (HRT) or no treatment (natural) for the endometrial preparation, regardless of their cycle number, from 1 January 2011 till 31 December 2015. Results A total of 2,752 FET cycles were included in our analysis. The natural cycle followed by vaginal progesterone support was used in 1,221 cycles and the HRT cycle with estrogen and vaginal progesterone was used in 1,531 cycles. There is a significantly higher miscarriage rate in the HRT group (38.4%) compared with the natural group (22.3%). The live birth rate is significantly higher in the natural group (22.8%) compared with the HRT group (17.3%). The multivariate analysis further shows that the HRT therapy is independently associated with an increased risk of miscarriage (adjusted odds ratio 2.05; 95% confidence interval 1.45–2.90; [Formula: see text] <0.001) and hence lower odds of live birth (adjusted odds ratio 0.69; 95% confidence interval 0.56–0.84; [Formula: see text] <0.001) after adjusting for the patient’s age at which the embryo was cryopreserved, race, body mass index, main indications for in vitro fertilization, number of embryos transferred and type of embryo transferred. Conclusion We have shown in this study that the miscarriage rate is higher in the HRT FET group and that this increased miscarriage rate translates into a lower live birth rate in the HRT group. Thus, we conclude that patients with regular menstrual cycles should be offered a natural FET cycle to achieve better outcomes in terms of live birth rate and reducing the miscarriage rate.

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
C Petriglia ◽  
A Vaiarelli ◽  
D Cimadomo ◽  
C Gentile ◽  
F Fiorini ◽  
...  

Abstract Study question Is the live-birth-rate (LBR) different when comparing artificial (AC) and modified-natural (M-NC) cycle for endometrial preparation to vitrified-warmed euploid blastocyst transfer? Summary answer The LBR after vitrified-warmed euploid blastocyst transfer seem independent of the endometrial preparation administered. What is known already Only the transfer of a competent embryo on a receptive endometrium might result in successful implantation. Three main protocols for endometrial preparation to vitrified-warmed embryo transfer exist: NC, M-NC, and AC. None among them, though, has been shown more appropriate than the others to date, especially since, only in a few studies, the analysis was restricted to single euploid blastocyst transfers to limit the impact of embryonic issues on implantation. In conclusion, no clear consensus exists and the choice is still largely based on menstrual/ovarian cycle characteristics and patient’s needs. Study design, size, duration All first vitrified-warmed single euploid blastocyst transfers performed between April–2013 and March–2020 were included in the analysis. Endometrial preparation was conducted with either an AC (N = 1211) or a M-NC (N = 673). The protocol was chosen based on patients’ logistical reasons. The primary outcome was the LBR per transfer. Sub-analyses based on blastocyst quality and day of development were conducted. Birthweight, gestational age, gestational and perinatal issues were secondary outcomes. Participants/materials, setting, methods AC: oral estradiol-valerate 3-times/day from day2–3 of the cycle until the endometrial thickness reached ≥7mm, then 600 mg/day of micronized progesterone. The transfer was conducted on day6 of progesterone administration. M-NC: an intramuscular dose of 10,000IU hCG was administrated when the leading follicle was &gt;17 mm and the endometrium was thicker than 7mm and trilaminar, plus 400 mg/day of micronized-progesterone as luteal phase support starting 36–40hr post-hCG. The transfer was conducted on day7 after trigger. Main results and the role of chance The two groups were similar for maternal age at retrieval (38.0±3.3yr) and transfer (38.3±3.3yr), reproductive history, embryological outcomes of the IVF cycle, body-mass-index, basal hormonal levels, and blastocyst features (Gardner’s classification: AA = 73%, AB/BA=11%, BB/AC/CA=8%, CC/BC/CB=8%; day5=48%, day6=47%, day7=5%). The LBR was 46.7% (N = 565/1211) and 49.9% (N = 336/673) after AC and M-NC, respectively, resulting in an odds-ratio 1.14, 95%CI:0.94–1.37. The absence of significant differences was confirmed also when adjusted for blastocyst quality and day of full-development (1.16, 95%CI:0.96–1.41). Among the 565 and 336 deliveries, the birthweight was similar (3290.3±470.7 versus 3251.7±521.5 g, Mann-Whitney-U-test=0.5), the gestational age was similar (38.5±1.7 versus 38.4±1.9 weeks, Mann-Whitney-U-test=0.5). Also, the rates of newborns who were normal (81% versus 82%), large (8% versus 9%), and small (11% versus 9%) for gestational age were similar (Chi-squared-test=0.5). The rates of patients experiencing gestational (6% versus 7%) and/or perinatal issues (3% versus 3%) were also similar (Fisher’s-exact-tests=0.4). Limitations, reasons for caution This is a retrospective study conducted in poor prognosis patients indicated to preimplantation genetic testing for aneuploidies. Future randomized controlled trials and cost-effectiveness analysis are desirable, as well as studies in different patient populations. Lastly, each gestational/perinatal issue shall be analyzed per se (e.g. different placentation disorders). Wider implications of the findings: The absence of clinical and perinatal differences between the two protocols for endometrial preparation supports the adoption, whenever needed, of AC. This approach, in fact, allows a higher flexibility in patients’ and daily workload management. Trial registration number None


2020 ◽  
Vol 02 (01) ◽  
pp. 32-36 ◽  
Author(s):  
Georgia Heathcote ◽  
Clare Boothroyd ◽  
Kevin Forbes ◽  
Alan Lee ◽  
Margaret Gregor ◽  
...  

Background: Polycystic ovary syndrome (PCOS) affects 5%-15% of women of reproductive age and has a negative impact on their fertility. The primary outcome of this study is ovulation rate when standard (immediate release) metformin (MF) is added to clomiphene citrate (CC) in oligoovulatory and anovulatory women with PCOS. Methods: This is a randomized, double-blind, placebo-controlled trial. Twenty-seven women with PCOS (according to the Rotterdam consensus), desiring pregnancy and without another cause of subfertility were recruited from a public hospital outpatient gynecology clinic. Up to six cycles of CC (25-150 mg) plus either MF 500 mg tds (CC+MF) or placebo (CC+Pl) were offered. Student’s t-test, Chi-squared test, and Fisher’s exact test were used for analysis. Results: Thirteen women with up to six cycles each were included in the final analysis. The rate of ovulation and ovulation rate per cycle was similar between women in the CC+MF and CC+Pl groups RR 1.09 (95% CI 0.80-1.49) and RR 0.88 (95% CI 0.63-1.22), respectively as was chemical pregnancy rate RR 1.77 (95% CI 0.58-5.38). The live birth rate was higher in CC+MF RR 6.83 (95% CI 0.83-56.27) and miscarriage rate was lower RR 0.21 (95% CI 0.002-1.07). The number needed to treat for live birth was 10. Conclusion: Use of standard MF, 500 mg tds, when given with CC results in an increase in live birth rate, and a decrease in miscarriage rate.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Junan Meng ◽  
Mengchen Zhu ◽  
Wenjuan Shen ◽  
Xiaomin Huang ◽  
Haixiang Sun ◽  
...  

Abstract Background It is still uncertain whether surgical evacuation adversely affects subsequent embryo transfer. The present study aims to assess the influence of surgical evacuation on the pregnancy outcomes of subsequent embryo transfer cycle following first trimester miscarriage in an initial in vitro fertilization and embryo transfer (IVF-ET) cycle. Methods A total of 645 patients who underwent their first trimester miscarriage in an initial IVF cycle between January 2013 and May 2016 in Nanjing Drum Tower Hospital were enrolled. Surgical evacuation was performed when the products of conception were retained more than 8 h after medical evacuation. Characteristics and pregnancy outcomes were compared between surgical evacuation patients and no surgical evacuation patients. The pregnancy outcomes following surgical evacuation were further compared between patients with ≥ 8 mm or < 8 mm endometrial thickness (EMT), and with the different EMT changes. Results The EMT in the subsequent embryo transfer cycle of surgical evacuation group was much thinner when compared with that in the no surgical evacuation group (9.0 ± 1.6 mm vs. 9.4 ± 1.9 mm, P = 0.01). There was no significant difference in implantation rate, clinical pregnancy rate, live birth rate or miscarriage rate between surgical evacuation group and no surgical evacuation group (P > 0.05). The live birth rate was higher in EMT ≥ 8 mm group when compared to < 8 mm group in surgical evacuation patients (43.0% vs. 17.4%, P < 0.05). Conclusions There was no significant difference in the pregnancy outcomes of subsequent embryo transfer cycle between surgical evacuation patients and no surgical evacuation patients. Surgical evacuation led to the decrease of EMT, especially when the EMT < 8 mm was association with a lower live birth rate.


2019 ◽  
Vol 34 (12) ◽  
pp. 2340-2348 ◽  
Author(s):  
Takeshi Sato ◽  
Mayumi Sugiura-Ogasawara ◽  
Fumiko Ozawa ◽  
Toshiyuki Yamamoto ◽  
Takema Kato ◽  
...  

Abstract STUDY QUESTION Can preimplantation genetic testing for aneuploidy (PGT-A) improve the live birth rate and reduce the miscarriage rate in patients with recurrent pregnancy loss (RPL) caused by an abnormal embryonic karyotype and recurrent implantation failure (RIF)? SUMMARY ANSWER PGT-A could not improve the live births per patient nor reduce the rate of miscarriage, in both groups. WHAT IS KNOWN ALREADY PGT-A use has steadily increased worldwide. However, only a few limited studies have shown that it improves the live birth rate in selected populations in that the prognosis has been good. Such studies have excluded patients with RPL and RIF. In addition, several studies have failed to demonstrate any benefit at all. PGT-A was reported to be without advantage in patients with unexplained RPL whose embryonic karyotype had not been analysed. The efficacy of PGT-A should be examined by focusing on patients whose previous products of conception (POC) have been aneuploid, because the frequencies of abnormal and normal embryonic karyotypes have been reported as 40–50% and 5–25% in patients with RPL, respectively. STUDY DESIGN, SIZE, DURATION A multi-centre, prospective pilot study was conducted from January 2017 to June 2018. A total of 171 patients were recruited for the study: an RPL group, including 41 and 38 patients treated respectively with and without PGT-A, and an RIF group, including 42 and 50 patients treated respectively with and without PGT-A. At least 10 women in each age group (35–36, 37–38, 39–40 or 41–42 years) were selected for PGT-A groups. PARTICIPANTS/MATERIALS, SETTING, METHODS All patients and controls had received IVF-ET for infertility. Patients in the RPL group had had two or more miscarriages, and at least one case of aneuploidy had been ascertained through prior POC testing. No pregnancies had occurred in the RIF group, even after at least three embryo transfers. Trophectoderm biopsy and array comparative genomic hybridisation (aCGH) were used for PGT-A. The live birth rate of PGT-A and non-PGT-A patients was compared after the development of blastocysts from up to two oocyte retrievals and a single blastocyst transfer. The miscarriage rate and the frequency of euploidy, trisomy and monosomy in the blastocysts were noted. MAIN RESULT AND THE ROLE OF CHANCE There were no significant differences in the live birth rates per patient given or not given PGT-A: 26.8 versus 21.1% in the RPL group and 35.7 versus 26.0% in the RIF group, respectively. There were also no differences in the miscarriage rates per clinical pregnancies given or not given PGT-A: 14.3 versus 20.0% in the RPL group and 11.8 versus 0% in the RIF group, respectively. However, PGT-A improved the live birth rate per embryo transfer procedure in both the RPL (52.4 vs 21.6%, adjusted OR 3.89; 95% CI 1.16–13.1) and RIF groups (62.5 vs 31.7%, adjusted OR 3.75; 95% CI 1.28–10.95). Additionally, PGT-A was shown to reduce biochemical pregnancy loss per biochemical pregnancy: 12.5 and 45.0%, adjusted OR 0.14; 95% CI 0.02–0.85 in the RPL group and 10.5 and 40.9%, adjusted OR 0.17; 95% CI 0.03–0.92 in the RIF group. There was no difference in the distribution of genetic abnormalities between RPL and RIF patients, although double trisomy tended to be more frequent in RPL patients. LIMITATIONS, REASONS FOR CAUTION The sample size was too small to find any significant advantage for improving the live birth rate and reducing the clinical miscarriage rate per patient. Further study is necessary. WIDER IMPLICATION OF THE FINDINGS A large portion of pregnancy losses in the RPL group might be due to aneuploidy, since PGT-A reduced the overall incidence of pregnancy loss in these patients. Although PGT-A did not improve the live birth rate per patient, it did have the advantage of reducing the number of embryo transfers required to achieve a similar number live births compared with those not undergoing PGT-A. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the Japan Society of Obstetrics and Gynecology and grants from the Japanese Ministry of Education, Science, and Technology. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A Liñá. Tegedor ◽  
I Elkhatib ◽  
A Abdala ◽  
A Bayram ◽  
K Ab. Ali ◽  
...  

Abstract Study question Is the live birth rate (LBR) in euploid frozen embryo transfer (FET) cycles affected by the endometrial thickness (EMT)? Summary answer A significantly higher LBR was observed in patients with an endometrial thickness of at least 7.5mm (46.24% vs. 54.63%) What is known already Parameters assessing the endometrium prior planning a FET include endometrial thickness, pattern and blood flow. The impact of the endometrial thickness on ART outcomes is controversial, with conflicting results published. A recent meta-analysis evaluated whether EMT could predict pregnancy outcomes and suggested that lower EMT was associated with lower incidence of clinical pregnancy rate (CPR), implantation rate (IR) and LBR. Due to heterogeneity of parameters evaluated between different publications, where embryos with unknown ploidy status were transferred, in conjunction with variability of stimulation protocols and the number of embryos transferred, the real effect of the EMT was difficult to infer. Study design, size, duration This was a two-center retrospective observational study including a total of 1522 euploid FET cycles between March 2017 and March 2020 at ART Fertility Clinics Muscat, Oman and Abu Dhabi, UAE. Participants/materials, setting, methods Trophectoderm biopsies were analyzed with Next Generation Sequencing (NGS). Vitrification/warming of blastocysts was performed using Cryotop method (Kitazato). EMT was measured by vaginal ultrasound prior initiating the progesterone administration (± 1 day) and LBR was recorded. Multivariate analysis was performed between LB outcomes and median EMT while controlling for confounding factors. Main results and the role of chance A total of 1522 FET cycles were analyzed: 975 single embryo transfer (SET) and 547 double embryo transfer (DET). The mean age of the patients was 33.38 years with a mean BMI of 27.1 kg/m2. FET were performed in EMT ranging from 3 to 15 mm and 50.52% resulted in a live birth. Though potentially all ranges of EMT were associated with LB, the median EMT in patients with LB was significantly higher than the median EMT of patients without LB (7.6mm vs. 7.4mm; p &lt; 0.001). The dataset was stratified into two groups based on the median EMT (7.5mm): &lt; 7.5mm (n = 744 cycles) and ≥ 7.5mm (n = 778 cycles). A significantly higher live birth rate was observed in ≥ 7.5mm group (46.24% vs. 54.63%. p = 0.0012). In multivariate analysis, EMT, FET endometrial preparation protocol, and number of embryos transferred were the main parameters influencing the chance to achieve LB: OR 1.10 [1.01–1.19], p &lt; 0.015 for the EMT; OR 1.84 [1.47–2.30], p &lt; 0.0001 for Natural Cycle protocol and OR 1.55 [1.25–1.93], p &lt; 0.0001 for DET. Intercept 0.18 [0.07–0.44] p &lt; 0.0002. Female age did not reach significance: OR 1.02 [1.00–1.04], p = 0.056. Limitations, reasons for caution Besides the retrospective nature of the study, the inter-observer variability in EMT assessment between different physicians is a limitation. The physician and embryologist performing the embryo transfer could not been standardized due to the multicenter design of the study. Wider implications of the findings: The EMT in FET may influence the LBR and should be considered as an important factor for the success of embryo transfer cycles. Whether these results can be extrapolated to fresh embryo transfer and to blastocysts with unknown ploidy status, needs further investigation. Trial registration number Not applicable


Author(s):  
Howard J.A. Carp

AbstractProgestational agents are often prescribed to prevent threatened miscarriage progressing to miscarriage, and subsequent miscarriages in recurrent pregnancy loss. Progestogens affect implantation, cytokine balance, natural killer cell activity, arachidonic acid release and myometrial contractility. A recent Cochrane review reported that progestogens were effective for treating threatened miscarriage with no harmful effects on mother or fetus. The results were not statistically different when vaginal progesterone was compared to placebo, (RR=0.47, 95% CI 0.17–1.30), whereas oral progestogen (dydrogesterone) was effective (RR=0.54, CI 0.35–0.84). The review concluded, that the small number of eligible studies, and the small number of the participants, limited the power of the metaanalysis. A later metaanalysis of five randomised controlled trials of threatened miscarriage comprised 660 patients. The results of 335 women who received dydrogesterone were compared to 325 women receiveing either placebo or bed rest. There was a 47% reduction in the odds ratio for miscarriage, (OR=0.47, CI 0.31–0.7). There was a 13% (44/335) miscarriage rate after dydrogesterone administration compared to 24% in control women. Recurrent miscarriage affects approximately 1% of women of child bearing age. A metaanalysis of progestational agents shows a 26% increase in the live birth rate. Again, dydrogesterone was associated with a more significant increase in the live birth rate than the other progestogens included in the metaanalysis.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yuchao Zhang ◽  
Wenbin Wu ◽  
Yanli Liu ◽  
Yichun Guan ◽  
Xingling Wang ◽  
...  

Purpose. To investigate the association between high-normal preconception TSH levels and reproductive outcomes in infertile women undergoing the first single fresh D5 blastocyst transfer. Methods. This was a retrospective study. Euthyroid patients undergoing the first single fresh D5 blastocyst transfer from January 2018 to May 2019 were initially included. The patients were divided into a low TSH (0.27–2.5 mIU/L) group and a high-normal TSH (2.5–4.2 mIU/L) group. The reproductive outcomes were compared between the groups. Results. A total of 824 women were ultimately included, 460 of whom had serum TSH levels less than 2.5 mIU/L and 364 of whom had serum TSH levels between 2.5 and 4.2 mIU/L. The patients were highly homogeneous in terms of general characteristics. High-normal TSH levels had no adverse impact on the clinical pregnancy rate, miscarriage rate, or live birth rate (respectively, aOR = 0.84, 0.65, 0.61, and P=0.234, 0.145, 0.083). No significant differences were observed in terms of gestational age, single live birth rates, birth weight, or birth length. Conclusion. High-normal TSH levels did not significantly influence reproductive outcomes in infertile women undergoing the first single fresh D5 blastocyst transfer. Further studies are needed to test whether the results might be applicable to a wider population.


2021 ◽  
Author(s):  
xiaoyue Shen ◽  
Min Ding ◽  
Yuan Yan ◽  
Shanshan Wang ◽  
jianjun Zhou ◽  
...  

Abstract Background To evaluate the frozen-thawed embryo transfer (FET) outcomes of repeated cryopreservation by vitrification of blastocysts derived from vitrified-warmed day3 embryos in patients who experienced implantation failure previously. Methods We retrospect the files of patients who underwent single frozen-thawed blastocyst transfer cycles in our reproductive medical center from January 2013 to December 2019. 127 patients transfer of vitrified-warmed blastocysts derived from vitrified-warmed day3 embryos were defined as twice-cryopreserved group. 1567 patients who transfer blastocysts that had experienced once vitrified-warmed were used as once-cryopreserved group. None of them was pregnant at the previous FET. The outcomes were compared between two groups after a 1:1 propensity score matching (PSM). Results The clinical pregnancy rate was 52.76%, live birth rate was 43.31% in twice-cryopreserved group. After PSM,108 pairs of patients were generated for comparison. The clinical pregnancy rate, live birth rate or miscarriage rate was not significantly different between two groups. Logistic regression analysis indicated that double vitrification-warming procedures did not affect FET outcomes in terms of clinical pregnancy rate (OR 0.83, 95%CI 0.47-1.42), live birth rate (OR 0.93, 95%CI 0.54-1.59), miscarriage rate (OR 0.72 95%CI 0.28-1.85). Furthermore, the pregnancy complications rate, gestational age or neonatal abnormalities rate between two groups was also comparable, while twice vitrification-warming procedures might increase the macrosomia rate (19.6% vs. 6.3%, P = 0.05). Conclusion Transfer of double vitrified-warmed embryo at cleavage stage and subsequent blastocyst stage did not affect live birth rate and neonatal abnormalities rate, but there was a tendency to increase macrosomia rate, which needs further investigation.


Author(s):  
Peng-Sheng Zheng ◽  
Shan Li ◽  
Jing Jing He

Background Parental abnormal chromosomal karyotypes are considered as reasons for recurrent pregnancy loss. Objective This systematic meta-analysis evaluated the current evidence on pregnancy outcomes amongst couples with abnormal versus normal chromosomal karyotypes. Search strategy Two independent reviewers screened titles and abstracts identified in EMBASE and PubMed from inception to January 2021. Selection criteria Studies were included if they provided a description of pregnancy outcomes of parental chromosomal abnormality. Data collection and analysis Random effects meta-analysis was used to compare odds of pregnancy outcomes associated with noncarriers and carriers. Main results A significantly lower first pregnancy live birth rate (FPLBR) was found in carriers than in noncarriers with RPL (OR: 0.55; 95% CI: 0.46-0.65; p<0.00001). Regarding FPLBR between translocation or inversion carriers and noncarriers, a markedly decreased FPLBR was found in translocation (OR: 0.44; 95% CI: 0.31–0.61; p<0.00001) but not inversion carriers. The accumulated live birth rate (ALBR) (OR: 0.96; 95% CI: 0.90–1.03; p=0.26) was similar, while the miscarriage rate (MR) of accumulated pregnancies (OR: 2.21; 95% CI: 1.69–2.89; p<0.00001) was significantly higher in the carriers than in noncarriers with RPL. The ALBR was not significant (OR: 1.82; 95% CI: 0.38–8.71; p=0.45) but the MR (OR: 5.75; 95% CI: 2.57–12.86; p<0.0001) was markedly lower for carriers who choose PGD than natural conception. Conclusions Carriers with RPL had higher risk of miscarriage but obtained a satisfying pregnancy outcome through multiple attempts. No sufficient evidence was found PGD could enhance the ALBR but it was an alternative to decrease the MR.


2020 ◽  
Author(s):  
XIN MU ◽  
Hui Wang ◽  
Pei-jun Liu ◽  
Juan-zi Shi

Abstract ObjectiveTo identify whether the time interval from insemination to ovulation (I-O interval) affects outcome after intrauterine insemination with donor sperm (IUI-D).DesignRetrospective study.SettingA single public medical center.Patient(s)1,165 couples, for 2,091 IUI-D cycles.Main Outcome MeasureLive birth rate (LBR) ResultsMultiple predictors were identified for LBR. The I-O interval was the predictor for LBR. An I-O interval ≥19 hours significantly decreased CPR (odds ratio [OR], 95% confidence interval [CI] =0.285, 0.171-0.475) and LBR (OR, 95%CI =0.322, 0.189-0.549). The presence of at least two follicles ≥18mm on ovulation day significantly increased the LBR (OR, 95%CI =1.274, 1.012-1.602). Women aged 35 years and older had a significant decreased LBR (OR, 95% CI =0.607, 0.377-0.976).Conclusion(s)The I-O interval, a new prognostic factor, combination with the women’s age and number of mature follicle, can predict the outcome after IUI-D. IUI-D is best performed within 19 hours of I-O interval for a higher probability of clinical pregnancy and live birth.


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