P–693 Gonadotropin stimulation reduces the implantation and live birth but not the miscarriage rate – a study based on the comparison of stimulated and unstimulated IVF

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
V Mitter ◽  
F Grädel ◽  
A S Koh. Schwartz ◽  
M Vo. Wolff

Abstract Study question Does gonadotropin stimulation in conventional IVF (cIVF) affect the implantation, miscarriage and live birth rates? Summary answer Gonadotropin stimulation negatively affects the implantation and live birth but not the miscarriage rate in IVF treatments. What is known already Literature hypothesizes that embryos derived from unstimulated, natural cycle IVF (NC-IVF) have a higher implantation potential compared to embryos from cIVF. In NC-IVF, recruitment of the leading follicle is based on natural selection. Hormonal stimulation might not only affect the embryo but also endometrial function. It’s possible to compare outcomes of NC-IVF and cIVF if cIVF is performed without embryo selection, in other words, if only those zygotes, which will be transferred 1–2 days later, are left in culture and all other zygotes are cryopreserved. To test this hypothesis, we compared success rates in NC-IVF and in cIVF. Study design, size, duration We performed a cohort study from 2011–2016 including data on IVF cycles with transfer of fresh embryos on day 2–3 at a University based infertility center. Our sample consisted of 640 women with 1482 embryos transferred in 996 cycles. We defined implantation rate as the number of sonograhically detected amniotic sacs per transferred embryos. Data originated from the Swiss ART registry “FIVNAT” and the Bern IVF Cohort and was completed using medical and delivery records. Participants/materials, setting, methods We defined NC-IVF as IVF without stimulation of follicular growth and cIVF as IVF with gonadotropin stimulation ≥75 IE/d and >3 retrieved oocytes. We performed zygote, but not embryo selection and transferred embryos on day 2–3. We calculated implantation and live birth per transferred embryo as binary outcomes using bi- and multivariable multilevel logistic regression models accounting for two clusters; the women and the cycle; and adjusting for maternal and infertility characteristics using STATA. Main results and the role of chance Age of women (p = 0.531), parity (p = 0.194) and type of infertility (primary vs secondary) (p = 0.463) did not differ between women undergoing NC-IVF or cIVF. In NC-IVF, 468 (31.6%) embryos were transferred, 450 as single, 18 as double transfers. In cIVF, 1014 (68.4%) embryos were transferred, 91 as single, 830 as double and 93 as triple transfers. Implantation rate was higher in NC-IVF. In NC-IVF 80 (17.1%) and in cIVF 132 (13.0%) embryos developed into an amniotic sac (OR 1.58; 95% CI 1.01–2.46; p = 0.042). After adjustment for maternal age (p < 0.001), parity (p < 0.001), type of infertility (p = 0.037), duration of subfertility and indication for IVF, aOR for implantation per transferred embryo increased to 1.87 (95% CI 1.21–2.91; p = 0.005). Miscarriage rate was similar. In NC-IVF and cIVF 25% (n = 20; n = 33) miscarried and 75% (n = 60; n = 99) ended in a live birth, respectively (OR 0.91; 95% CI 0.32–2.60; p = 0.855; aOR 1.0; 95% CI 0.42–2.36; p = 1.000). Live birth rate per transferred embryo was increased in NC-IVF; 60 of 468 (12.8%) embryos in NC-IVF compared to 99 of 1041 (9.8%) embryos in cIVF resulted in a live birth (OR 1.51; 95% CI 0.92–2.49; p = 0.106); and became significantly higher after adjustment (aOR 1.85; 95% CI 1.16–2.95; p = 0.010). Limitations, reasons for caution This study analyses observational data from a clinic offering NC-IVF and cIVF treatment as equivalent options. NC-IVF is a model for natural fertility and allows us to study the impact of gonadotropins. However, it is not a randomised study and therefore prone to selection bias. Wider implications of the findings: The study suggests that gonadotropin stimulation might reduce the implantation potential and subsequently live birth rates, by possibly affecting embryo and endometrium quality. Clinicians should consider lower gonadotropin doses for stimulation. Trial registration number Not applicable

2020 ◽  
Vol 9 (8) ◽  
pp. 2478
Author(s):  
Lisa Boucret ◽  
Pierre-Emmanuel Bouet ◽  
Jérémie Riou ◽  
Guillaume Legendre ◽  
Léa Delbos ◽  
...  

Endometriosis and infertility are closely linked, but the underlying mechanisms are still poorly understood. This study aimed to evaluate the impact of endometriosis on in vitro fertilization (IVF) parameters, especially on embryo quality and IVF outcomes. A total of 1124 cycles with intracytoplasmic sperm injection were retrospectively evaluated, including 155 cycles with endometriosis and 969 cycles without endometriosis. Women with endometriosis had significantly lower ovarian reserve markers (AMH and AFC), regardless of previous ovarian surgery. Despite receiving significantly higher doses of exogenous gonadotropins, they had significantly fewer oocytes, mature oocytes, embryos, and top-quality embryos than women in the control group. Multivariate analysis did not reveal any association between endometriosis and the proportion of top-quality embryo (OR = 0.87; 95% CI [0.66–1.12]; p = 0.3). The implantation rate and the live birth rate per cycle were comparable between the two groups (p = 0.05), but the cumulative live births rate was significantly lower in in the endometriosis group (32.1% versus 50.7%, p = 0.001), as a consequence of the lower number of frozen embryos. In conclusion, endometriosis lowers the cumulative live birth rates by decreasing the number of embryos available to transfer, but not their quality.


Zygote ◽  
2021 ◽  
pp. 1-6
Author(s):  
Linjun Chen ◽  
Zhenyu Diao ◽  
Jie Wang ◽  
Zhipeng Xu ◽  
Ningyuan Zhang ◽  
...  

Summary This study analyzed the effects of the day of trophectoderm (TE) biopsy and blastocyst grade on clinical and neonatal outcomes. The results showed that the implantation and live birth rates of day 5 (D5) TE biopsy were significantly higher compared with those of D6 TE biopsy. The miscarriage rate of the former was lower than that of the latter, but there was no statistically significant difference. Higher quality blastocysts can achieve better implantation and live birth rates. Among good quality blastocysts, the implantation and live birth rates of D5 and D6 TE biopsy were not significantly different. Among fair quality and poor quality blastocysts, the implantation and live birth rates of D5 TE biopsy were significantly higher compared with those of D6 TE biopsy. Neither blastocyst grade nor the day of TE biopsy significantly affected the miscarriage rate. Neonatal outcomes, including newborn sex, gestational age, preterm birth, birth weight and low birth weight in the D5 and D6 TE biopsies were not significantly different. Both blastocyst grade and the day of TE biopsy must be considered at the same time when performing preimplantation genetic testing–frozen embryo transfer.


Biology ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 430
Author(s):  
María Gil Juliá ◽  
Irene Hervás ◽  
Ana Navarro-Gómez Lechón ◽  
Fernando Quintana ◽  
David Amorós ◽  
...  

The application of MACS non-apoptotic sperm selection in infertility clinics is controversial since the published literature does not agree on its effect on reproductive outcomes. Therefore, it is not part of the routine clinical practice. Classical measures of reproductive success (pregnancy or live birth rates per ovarian stimulation) introduce a bias in the evaluation of a technique’s effect, since only the best embryo is transferred. This retrospective, multicenter, observational study evaluated the impact of MACS on reproductive outcomes, measuring results in classical parameters and cumulative live birth rates (CLBR). Data from ICSI cycles using autologous oocyte in Spanish IVIRMA fertility clinics from January 2008 to February 2020 were divided into two groups according to their semen processing: standard practice (reference: 46,807 patients) versus an added MACS sperm selection (1779 patients). Only when measured as CLBR per embryo transferred and per MII oocyte used was the difference between groups statistically significant. There were no significant differences between MACS and reference groups on pregnancy and live birth rates. In conclusion, results suggest that non-apoptotic sperm selection by MACS on unselected males prior to ICSI with autologous oocytes has limited clinical impact, showing a subtle increase in CLBR per embryo transferred.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
P Sokol ◽  
E Clu. Obradó ◽  
M Sol Inarejos ◽  
M Parrieg. Beltrán ◽  
F Martíne. Sa. Andrés ◽  
...  

Abstract Study question Are embryo quality and day of vitrification (Day 5, 6 or 7) associated with live birth rates (LBR) following single blastocyst transfer (SBT) in frozen embryo transfer cycle (FET)? Summary answer Both blastocyst quality and day of vitrification are significantly associated with LBRs, with very low LBR when poor quality embryos are frozen on day 6. What is known already Evidence suggests that chromosomal status (ploidy) is strongly associated with blastocyst morphology and good quality embryos are more likely to be euploid. Furthermore, previous studies have shown a relationship between the time that embryos need to reach blastocyst stage and their euploidy rate with slowly developing blastocysts showing higher rate of aneuploidy. Nonetheless, despite all this evidence little is known about the actual effect of the combination of blastocyst quality and day of its vitrification. The scope of this study was to quantify the actual effect of the embryo quality and day of vitrification on live birth rates following FET. Study design, size, duration Retrospective analysis of 1546 FET cycles with SBT conducted between 2017 and 2019 in the university-affiliated private clinic. The embryos used for FET were obtained from IVF/ICSI: with PGT (FET-PGT) or without PGT (FET0) or from donated oocytes (FET-DON). Participants/materials, setting, methods FET with natural, natural-modified and completely medicated cycles to prepare endometrial lining were included. Blastocysts were classified according to Spanish Association for the Study of Reproductive Biology (ASEBIR) classification, ranging from A (the highest) to D (the lowest). The impact on LBR of different subgroups, formed within FET-PGT, FET0, FET-DON groups due to different day of vitrification and blastocyst quality, was assessed, using logistic regression after adjusting for age, day of vitrification and embryo quality. Main results and the role of chance We included 1546 FET cycles. Of those, 543 (35%) corresponded to FET-PGT; 648 (42%) to FET0 and 355 (23%) to FET-DON cycles. Overall, 1051 (68%) embryos were frozen on day 5(D5), 472 (30.5%) on day 6(D6) and 23 (1.5%) on day 7(D7). As far as embryo quality was concerned, 215 (13.9%) grade A; 957 (61.9%) B; 371(24%) C and 3(0.2%) D blastocysts were transferred. LBRs were significantly different between different embryos frozen on D5 44.3%; on D6 28.8% and on D7 8.7%, p < 0.001. When blastocyst quality was considered, LBR were 48.4% for grade A; 42.5% for B; 25.1% for C and 0% for D, p < 0.001. After applying logistic regression analysis, the odds ratio (OR) for transferring D6-blastocyst was 1.08, 95% CI[0.45; 2.62] and blastocyst with grade B and C; 0.71, 95% CI[0.51; 1.00]; 0.57,95% CI[0.36; 0.88] respectively. However, after transferring D6-blastocyst graded as C, the OR was 0.33, 95% CI[0.12; 0.90]. Our predictive model showed that the impact of the embryo quality on LBR was sustained across three groups. Transfer of D5/D6 grade A blastocyst resulted in the highest, while D6-C in the lowest LBR in all the groups. In the latter case vitrification on D6 impaired additionally the outcome. Limitations, reasons for caution The study should be interpreted with caution due to its retrospective character and the assessment of blastocyst quality on the day of vitrification and not on the day its transfer. Wider implications of the findings: Our robust findings could be considered a useful tool for counselling couples who seek advice regarding their expected success rates in the setting of FET with SBT. The very low livebirth rates in low quality (C) slow developing (D6) embryos should be communicated to patients prior to planning a FET. Trial registration number Not applicable


2013 ◽  
Vol 16 (3) ◽  
pp. 211-214 ◽  
Author(s):  
Dave R. Listijono ◽  
Tim Boylan ◽  
Simon Cooke ◽  
Suha Kilani ◽  
Michael G. Chapman

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
R Maggiulli ◽  
D Cimadomo ◽  
L Dovere ◽  
F Innocenti ◽  
L Albricci ◽  
...  

Abstract Study question Is cryo-storage duration associated with the outcomes after vitrified-warmed euploid single blastocyst transfer? Summary answer Lower live-birth-rates from blastocysts cryo-stored for periods longer than 3-months are mostly imputable to the worse quality of the embryos being warmed across sequential transfers. What is known already Blastocyst vitrification is crucial in modern IVF. Given its widespread application, a constant comprehensive monitoring of its effect on reproductive outcomes is pivotal. For instance, the effect of cryo-storage duration on embryo implantation potential, gestational and perinatal outcomes is object of a still ongoing investigation. The evidence in this regard are contrasting especially with regard to similar or decreased live birth rates among blastocysts subject to long-term cryo-storage. When investigating the neonatal outcomes, instead, no impact of blastocyst cryo-storage duration has ever been reported to date. Yet, data on euploid blastocysts and adjusted for quality and full-blastulation day are needed. Study design, size, duration Retrospective observational study. We included 2688 vitrified-warmed euploid single blastocyst transfers. The primary outcome was the live-birth-rates (LBR) according to cryo-storage duration clustered as ≤ 60, 61-90, 91-180, 181-360, 361-720, 721-1080 and >1080-days. The secondary outcomes were the miscarriage rate, the rates of gestational and perinatal issues among the deliveries, and the mean gestational age and birthweight among the babies born. All data were adjusted for confounders through linear or logistic regression analyses. Participants/materials, setting, methods We included all vitrified-warmed transfers (range:1-8) conducted between May-2013 and March-2020 by 1884 patients (age:38±3yr) undergoing one blastocyst stage PGT-A cycle and obtaining ≥1 euploid embryo at our private clinic. Among putative confounders, only the number of sequential transfer from the same patient, blastocyst quality (Gardner’s scheme) and full-blastulation day (5-7) significantly associated with the LBR through univariate regressions. No association was reported for sperm factor, maternal age, incubator, and culture media. Main results and the role of chance The LBR of euploid blastocysts cryo-stored for ≤60-days was 49.4% (N = 319/646) versus 48.7% (N = 292/599; OR:0.98,95%CI:0.78-1.21,p = 0.82) between 61-90-days, 42.9% (N = 291/679; OR:0.77,95%CI:0.62-0.96,p = 0.02) between 91-180-days, 41.7% (N = 169/405; OR:0.73,95%CI:0.57-0.94,p = 0.02) between 181-360-days, 34.7% (N = 50/144; OR:0.55,95%CI:0.37-0.79,p < 0.01) between 361-720-days, 53.4% (N = 63/118; OR:1.17,95%CI:0.79-1.74,p = 0.42) between 721-1080-days, and 50.5% (N = 49/97; OR:1.05,95%CI:0.68-1.60,p = 0.83) for >1080-days. However, when these data were adjusted for blastocyst quality and full-blastulation day, all the multivariate-OR were not-significant. Indeed, the longer the cryo-storage period the worse the quality of the euploid blastocysts transferred (e.g. AA-blastocysts were 74% among embryos cryo-stored for ≤90-days, but always < 70% for embryos cryo-stored for longer periods, p < 0.01; similarly, day5-blastocysts were ∼50% among embryos cryo-stored for ≤90-days, but always < 50% for embryos cryo-stored for longer periods, p = 0.02). The miscarriage-rate (overall 14%, ranging 7-18%) was not associated with cryo-storage duration already from univariate regressions. Also the gestational (overall 6%, ranging 0-8%) and perinatal issues rates (overall 3%, ranging 0-5%) were not associated with cryo-storage duration already from the univariate regressions. Neither the gestational age nor the birthweight showed significant associations with cryo-storage duration, as confirmed by linear regressions. In fact the rate of newborns whose weight was normal-for-gestational-age was similar across all cryo-storage duration groups (overall 81%, ranging 80-83%). Limitations, reasons for caution The prevalence of first transfers decreases from ≥95% for procedures conducted ≤90-days from vitrification to 71%, 39%, 22% and 4% for procedures conducted between 91-180, 181-360, 361-720 and >720-days, respectively. However, also the sequential number of transfer was not associated with the LBR when adjusted for blastocyst-quality and full-blastulation day. Wider implications of the findings Cryo-storage by vitrification is confirmed safe in the hands of experienced operators, and its duration does not impact any outcome. This information is valuable for freeze-all cycles, but also for women cryo-preserving surplus embryos for second pregnancies; in this regard, 6.8% of the patients in this study delivered ≥2 LBs. Trial registration number not applicable


2021 ◽  
Vol 7 ◽  
Author(s):  
Jianyuan Song ◽  
Tingting Liao ◽  
Kaiyou Fu ◽  
Jian Xu

Objectives: Unexplained infertility has been one of the indications for utilization of intracytoplasmic sperm injection (ICSI). However, whether ICSI should be preferred to IVF for patients with unexplained infertility remains an open question. This study aims to determine if ICSI improves the clinical outcomes over conventional in vitro fertilization (IVF) in couples with unexplained infertility.Methods: This was a retrospective cohort study of 549 IVF and 241 ICSI cycles for patients with unexplained infertility at a fertility center of a university hospital from January 2016 and December 2018. The live birth rate and clinical pregnancy rate were compared between the two groups. Other outcome measures included the implantation rate, miscarriage rate, and fertilization rate.Results: The live birth rate was 35.2% (172/488) in the IVF group and 33.3% (65/195) in ICSI group, P = 0.635. The two groups also had similar clinical pregnancy rates, implantation rates, and miscarriage rates. The fertilization rate of IVF group was significantly higher than that of ICSI group (53.8 vs. 45.7%, P = 0.000, respectively). Sixty-one and 46 patients did not transfer fresh embryos in IVF and ICSI cycles, respectively. Patients with IVF cycles had lower cancellation rates than those with ICSI (11.1 vs. 19.1%, P = 0.003, respectively).Conclusion: ICSI does not improve live birth rates but yields higher cancellation rates than conventional IVF in the treatment of unexplained infertility.


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