A simplified method of timing frozen embryo transfers

Objective: Our purpose was to compare a simple artificial hormone replacement regimen with two other protocols incorporating pituitary down-regulation with gonadotropin-releasing hormone agonist for frozen embryo transfers.Study design: We performed a retrospective analysis of pregnancy outcomes after 366 frozen embryo transfers times by one of three hormone replacement regimens. The three regimens used were regimen A, leuprolide acetate and transdermal estradiol patches; regimen B, leuprolide acetate and oral micronized estradiol; regimen C, only oral micronized estradiol.Results: The outcomes of 366 consecutive frozen embryo transfers according to one of the three regimens were compared and analyzed. The clinical pregnancy rates were 13.7%, 11.4% and 13.5% in regimens A, B and C, respectively. No statistical differences were found among the three regimens. The mean age of the patients in the three groups was comparable. The mean number of frozen embryos transferred with regimen B was slighly higher, but it did not have a positive impact on the pregnancy rate in this group.Conclusion: Controlled sequential hormone replacement results in an endometrium suitable for frozen embryo transfers. Pituitary down-regulation is not necessary. Therefore this regimen is not only more simple to use but also more economical.     

Intramuscular route of progesterone administration increases pregnancy rates during non-downregulated frozen embryo transfer cycles

Objective The optimal route of progesterone (P4) administration in embryo transfer (FET) cycles remains to be determined. The objective of this study is to compare the pregnancy outcomes between intramuscular (IM) and vaginal progesterone (PV) administration for endometrial preparation in non-donor FET cycles. Study design A retrospective clinical study in a private practice infertility setting. Results No significant differences in patient demographics and embryo characteristics were noted between the two groups. The clinical pregnancy rate as well as the live birth rate were significantly higher in the IM arm compared to the PV arm (38.2% vs 28%, 34.5 % vs 22.8%, respectively). Conclusion Although both routes of progesterone administration had similar rates of initial positive pregnancy tests, the IM route had a significantly higher live birth rate. The exact reason for this difference remains to be determined.     

Blastocyst age,expansion, trophectoderm morphology,and number cryopreserved are variables predicting clinical implantation in single blastocyst frozen embryo transfers in freeze-only-IVF

PurposeTo determine which blastocyst assessment variables predict clinical implantations in single blastocyst frozen embryo transfers (FET) of freeze-only-IVF cycles, following improved vitrified-warmed blastocyst survival and developmental competence preservation.MethodIn this retrospective cohort study performed at a single private IVF center, the pregnancy outcomes of 1795 single blastocyst FET cycles were analyzed, from freeze-only-IVF retrievals performed between January 2017 and January 2020. Stepwise forward logistic regressions with clinical implantation (i.e., normal gestational sac and cardiac activity) as dependent variable were performed to identify the significant predictors. All blastocysts were vitrified using Cryotop technology, with before transfer (post-warming) blastocyst morphology scores used in all analyses.Result(s)The 1795 blastocysts transferred were vitrifıed on embryo days 4 (1057), 5 (716), and 6 (22). The overall clinical implantation rate was 50.9%; however, using blastocyst age and blastocyst morphological score the clinical implantation rates increased from 49.0% (day-4 1 and 2) and 25.2% (day-5 1 and 2) to 71.2% (day-4 4AA) and 64.3% (day-5 4AA), respectively. Whereas full (≥3) blastocysts with scores of AA and BA had similar clinical implantation rates (66.2 vs. 66.7%), the rate of full blastocysts with scores of AB was lower (58.9%). In stepwise forward logistic regressions, female age, blastocyst age, blastocyst expansion score, blastocyst trophectoderm score, and number of blastocysts vitrified were significant predictors of clinical implantation.Conclusion(s)Using blastocyst age and before transfer blastocyst expansion and trophectoderm morphology scores to select blastocysts, clinical implantation rates greater than 70% could be achieved for top-scoring blastocysts.     

Frozen-thawed embryo transfer cycles in China: clinical outcomes of two and three multicellular embryos transfers

Purpose

To analyze the clinical outcomes of frozen embryo transfer (FET) cycles when two or three multicellular embryos were transferred in Chinese women.

Methods

A retrospective study was conducted to analyze 980 FET cycles performed between January 2007 and October 2010. Two (785 cycles) or three (195 cycles) multicellular embryos were transferred.

Results

Both in patients under 35 years (n = 776) and those aged 35 to 39 years (n = 169), the transfer of two versus three multicellular embryos results in similar clinical pregnancy rates (CPR), implantation rates (IR) and live birth rates (LBR). In both age groups, the multiple pregnancy rate (MPR) was significantly higher in the three-embryo groups. Among women over 40 years of age (n = 35), there were no differences in the CPR, IR, MBR or LBR between the two groups

Conclusions

Transferring two instead of three multicellular embryos in patients under 40 years old significantly decreases the risk of MPR without compromising PR, IR and LBR. In the age group above 40, transferring two instead of three multicellular embryos did not decrease PR, IR, MBR or LBR. Transferring more embryos when a patient had more unsuccessful cycles was not warranted in all patients.     

Serum progesterone concentration and live birth rate in frozen–thawed embryo transfers with hormonally prepared endometrium

Research question

Is serum progesterone measurement on the day of embryo transfer associated with outcome of frozen–thawed embryo transfer (FET) in cycles using hormonal replacement therapy (HRT) for endometrium preparation?

Blastocyst culture after repeated failure of cleavage-stage embryo transfers: a comparison of day 5 and day 6 transfers

OBJECTIVE: To evaluate the efficacy of blastocyst transfer among patients with at least three previous cleavage-stage embryo transfer failures and to compare pregnancy and implantation rates of blastocysts according to the day of embryo transfer (day 5 or day 6 after oocyte retrieval). DESIGN: Retrospective clinical study. SETTING: Private ART center. PATIENT(S): One hundred forty-eight patients (with at least three failed cleavage-stage embryo transfers) undergoing blastocyst-stage embryo transfer. INTERVENTION(S): Embryos were grown for up to 6 days and only blastocyst-stage (cavitating) embryos were transferred on either day 5 or day 6 after oocyte retrieval. MAIN OUTCOME MEASURE(S): Clinical pregnancy and implantation rates. RESULT(S): Blastocysts transferred on day 5 implanted almost five times the rate of those transferred on day 6 (23% vs. 5%). Pregnancy rates were triple as high among the 73 day 5 patients compared to the 63 day 6 transfer patients (38% vs. 11%). The number of blastocysts formed and per embryo rates of blastocyst formation were both significantly higher for patients undergoing day 5 transfers: more blastocysts developed (3.0 vs. 2.1) and more were transferred (3.0 vs. 1.9). In addition, blastocyst formation rates were 46% and 33%, respectively, for both groups of patients. CONCLUSION(S): Blastocyst transfer (preferably on day 5 after retrieval) appears to be a successful and improved alternative for patients with multiple failed IVF attempts. Moreover, with blastocyst transfer there should be a reduction in multiple pregnancy risk, because fewer embryos have to be transferred.     

Blastocyst-stage versus cleavage-stage embryo transfer in the first frozen cycles of OHSS-risk patients who deferred from fresh embryo transfer

Abstract

Elective cryopreservation of all embryos has been the most effective means to avoid developing ovarian hyperstimulation syndrome (OHSS). However, it is still unknown which stage is optimal for freezing and transferring into uterus in OHSS-risk patients. This study was undertaken to evaluate whether OHSS-risk patients could benefit from transferring blastocysts. A total of 162 women were allocated to cleavage-stage embryo transfer (ET) (group A?=?70) and blastocysts transfer (group B?=?92) on the basis of patients’ voluntary in their first frozen cycles. Although the mean number of transferred embryos in group A was significantly more than those in group B (2.37?±?0.52 versus 2.11?±?0.52, p?<?0.05), the clinical pregnancy rates, implantation rates and live birth rates in group B were significantly higher than those in group A (47.83% versus 31.43%, p?<?0.05; 31.44% versus 18.67%, p?<?0.05; 40.21% versus 27.14%, p?<?0.05), and the multiple pregnancy rates in both groups were comparable (34.09% versus 36.36%, p?>?0.05). The observed results in OHSS-risk population allow us to take a position in favor of blastocyst transfer, thus pregnancy and live birth could be achieved with fewer ETs and in a shorter time frame.     

Gender bias in the disposition of frozen embryos

Objective: To examine the gender differences found among couples when choosing the disposition of their frozen embryos.

Design: Retrospective chart review.

Setting: University affiliated in vitro fertilization (IVF) center.

Patients: Couples undergoing their first cycle of assisted reproductive technology (ART).

Intervention(s): None.

Main Outcome Measure(s): Choice of disposition of gametes and embryos.

Result(s): Gender bias is found when couples choose the dispositon of their frozen embryos, but not when they choose the disposition of their gametes.

Conclusion(s): Gender bias was found in couples who made decisions regarding the disposition of their frozen embryos.     

Ectopic pregnancy rates in frozen versus fresh embryo transfer in in vitro fertilization: A systematic review and meta-analysis

ObjectiveTo evaluate whether the rate of ectopic pregnancy differs between fresh and frozen embryo transfers.DesignSystematic review and meta-analysis.SettingCenters for reproductive care.Materials and methodsAn electronic literature search in MEDLINE through PubMed was performed through December 2013. We included clinical trials comparing outcomes of in vitro fertilization (IVF) cycles between fresh and frozen embryo transfers.Main outcome measuresEctopic pregnancy rates from fresh versus frozen IVF cycles.ResultsA meta-analysis revealed no significant difference between ectopic pregnancy rates in fresh versus frozen embryo transfer. Similarly, there was no difference between ectopic pregnancy rates in natural-cycle frozen embryo transfer versus programmed cycles.ConclusionsDifferences in the hormonal milieu of the uterine environment between fresh and frozen embryo transfer stimulation do not appear to affect the ectopic pregnancy rate. More directed studies are needed before a definite recommendation can be made as to which is safer for prevention of ectopic pregnancy– fresh or frozen embryo transfer.     

Effects of three pro-nuclei (3PN) proportion incidence on clinical outcomes of patients with lower retrieved oocytes in the fresh cleavage-stage embryo transfer (ET) cycles

Purpose: To analyze the three pro-nuclei (3PN) incidence on clinical outcomes of patients with lower retrieved oocytes in the fresh cleavage-stage embryo transfer (ET) cycles.

Methods: This study included 1200 fresh cleavage-stage ET cycles from January 2013 to June 2015. The patients were divided into 3PN?=?0% (773 cycles) and 3PN?>?0% (427 cycles) group. Main outcomes compared were fertilization, cleavage, normal fertilization, good quality embryo, implantation, clinical pregnancy, and early abortion rate.

Results: We observed that there was no significant difference in female's age, the number of retrieved oocytes, the number of transferred embryos, the number of good quality embryos, endometrial thickness, infertile time, basal serum follicle-stimulating hormone, and E2 value between two groups (p?>?0.05). The fertilization (89.43 versus 83.90%, p?<?0.001) and cleavage (98.34 versus 97.19%, p?=?0.048) rates were significantly higher in 3PN?>?0% than 3PN?=?0% group. However, the normal fertilization (70.05 versus 50.67%, p?<?0.001), good quality embryos (37.11 versus 26.47%, p?<?0.001), and clinical pregnancy (49.81 versus 43.79%, p?=?0.046) rates were significantly higher in 3PN?=?0% than 3PN?>?0% group. The implantation (35.88 versus 33.78%, p?=?0.333) and early abortion (8.83 versus 10.70%, p?=?0.474) rates were not significantly different between two groups.

Conclusion: 3PN incidence might make a negative effect on clinical outcomes for patients with lower retrieved oocytes in the fresh cleavage-stage ET cycles.     

Live birth rate in fresh and frozen embryo transfer cycles in women with endometriosis

Objectives

To test the hypothesise that the treatment protocol used for preparation of the endometrium for frozen embryo transfer (ET) has a beneficial effect on the disorganised endometrium in women with endometriosis and leads to a higher pregnancy rate.

Study design

We performed a retrospective, database-searched cohort study. Relevant information was collected from the electronic records of women who underwent IVF/ICSI between 1/1/2000 and 31/12/2008 in our unit. Endometriosis patients formed the study group. The rest of the women formed the control group. The two groups were subdivided, depending on whether they had fresh or frozen ET. The main outcome was live birth rate (LBR). Secondary outcomes were clinical pregnancy rate (CPR) and miscarriage rate (MR). Comparisons were performed by Chi-square and Mann-Whitney tests (SPSS 16.0).

Results

A total of 3763 fresh and 3523 frozen ET IVF cycles were included in our study, of which 415 (5.7%) were due to endometriosis related subfertility. In the non-endometriosis group, fresh ET had significantly higher LBR, CBR and MR than frozen ET. In women with endometriosis, down-regulated frozen ET cycles had a markedly high LBR and CPR (16.9%, 18.2%), comparable to the LBR and CPR of fresh ET cycles in the same group (19.5%, 20.2%). No significant differences were found in the LBR and CPR in fresh ET cycles between the study and the control group. In frozen ET, however, the CPR was significantly higher in the endometriosis group (18.2% versus 12.7%, P = 0.048).

Conclusion

Unlike the general IVF population, in women with endometriosis undergoing IVF, the preparation of the endometrium for frozen ET with GnRH agonists compared to fresh cycles is associated with higher LBR (16.9% versus 11.9%) and a significantly higher CPR (18.2% versus 12.7%, P = 0.048). These results suggest that, in cases of endometriosis, the combined effect of GnRHa on the endometrium and the low level of ovarian steroids may simultaneously offer a better endometrial environment for implantation which may lead to better outcomes.     

Single and double embryo transfer provide similar live birth rates in frozen cycles

Abstract

Research question: Do live birth rates (LBRs) differ in frozen cycles of women who received single versus double embryo transfer?

Design: Retrospective cohort study including women who underwent their first frozen embryo transfer (FET) in a tertiary referral University Hospital between 2009–2014.

Results: 3601 patients were included in the analysis with 1936 (53.8%) having a single embryo transfer (SET) and 1665 (46.2%) having a double embryo transfer (DET). Overall, 657/3601 (18.24%) had a live birth. LBR were similar between SET and DET either for cleavage [100/757 (13.1%) versus 153/1032 (14.8%), p?=?.33] or blastocyst stage FET [256/1179 (21.7%) versus 148/633 (23.4%), p?=?.4). Ongoing pregnancy rates were comparable between DET and SET [316/1665 (18.9%) versus 359/1936 (18.5%)]. Multiple delivery rates were significantly higher in women with DET compared to SET [53/316 (16.7%) versus 7/359 (1.9%), p?<?.001]. Multivariate logistic regression analysis allowing adjustment for relevant confounders showed that the number of embryos transferred in the frozen cycle was not related to LBR.

Conclusions: This is the largest study providing evidence that both SET and DET may result in similar LBR, albeit multiple pregnancy rates are significantly lower in case of SET. Therefore, SET should be the main strategy in women undergoing FET.     

薄型子宫内膜新鲜胚胎和冻融胚胎移植妊娠结局比较

目的探讨在薄型子宫内膜患者中新鲜胚胎移植与冻融胚胎移植(FET)妊娠结局的差异。方法回顾性分析接受体外受精/卵胞质内单精子显微注射-胚胎移植(IVF/ICSI-ET)治疗采用长方案胚胎移植h CG注射日与冻融周期胚胎移植内膜转化日的内膜厚度≤7 mm的患者共592个周期的临床资料。将移植周期按胚胎是否冻融分为新鲜胚胎移植组(n=173)和FET组(n=419)。比较组间的胚胎种植率、临床妊娠率、流产率、多胎率和异位妊娠率有无差异。结果新鲜胚胎移植组患者平均移植胚胎(2.1±0.4)枚,与FET组患者平均移植胚胎(2.1±0.5)枚比较,组间有统计学差异(P0.05);按照移植胚胎数分为3个亚组,新鲜胚胎移植组1枚胚胎者,妊娠率为7.7%,2枚者为30.2%,3枚者为23.8%;FET组1枚胚胎者15.6%,2枚者为34.9%,3枚者为41.6%,新鲜胚胎移植组与FET组间差异均无统计学意义(P0.05)。组间着床率、流产率、异位妊娠率等结果也均无统计学差异(P0.05)。移植3枚胚胎新鲜组多胎率(80.0%)高于FET组(29.7%)(P0.05)。新鲜胚胎移植组多胎率3个亚组间有统计学差异(P0.05),FET组妊娠率和流产率3个亚组间均有统计学差异(P0.05)。将移植胚胎数作为协变量,纳入Logistics回归模型对结果变量进行分析,说明周期类型与临床妊娠率间无显著相关性(OR=0.726,95%CI=0.504~1.104)。结论子宫内膜厚度≤7 mm的薄型内膜患者新鲜胚胎移植和FET妊娠结局相似,选择新鲜周期移植不影响妊娠结局并可缩短治疗周期,降低总费用。     

Cryopreservation of human embryos at the morula stage and outcomes after transfer

OBJECTIVE: To evaluate the survival rate of human morula embryo freezing and the morphological alterations during freezing, during and after thawing, and their applications in embryo selection. DESIGN: Retrospective observational study. SETTING: Private infertility clinic. PATIENT(S): Consecutive patients under age 39 undergoing frozen morula embryo transfers from December 1999 to May 2003. INTERVENTION(S): Embryo freezing was performed at the morula stage. Embryo thaw and post-thaw ETs were conducted on the same day, which is equivalent to a day 4 ET. MAIN OUTCOME MEASURE(S): Morphological alterations during freezing and thawing and after thawing. Post-thaw embryo survival rates, transferable rates, pregnancy rates, and implantation rates. RESULT(S): Morula embryos showed reversed morphological alterations during the freezing process; these alterations were recovered during thawing or shortly after the thawing. Post-thaw survival rates showed no significant difference between any of the morula substages. However, embryos scored as grade 3, which represented good quality, had significantly higher post-thaw survival and transferable rates than grade 2 and 1 embryos. Patients who received at least one grade 3 embryo had significantly higher pregnancy rates, implantation rates, and ongoing/live birth rates than other groups. CONCLUSION(S): An acceptable survival rate can be achieved after cryopreservation of human morula embryos, and morphological alterations that occur during and shortly after an embryo thaw can be a feasible index for determining viable embryos.