Frozen-thawed Embryo Transfer Cycles Research Articles

Comparison of two mainstream endometrial preparation regimens in vitrified–warmed embryo transfers after PGT

Research questionWhich of the two mainstream endometrial preparation regimens, assisted natural cycle (NC) or hormone replacement treatment cycle (HRT), help frozen–thawed embryo transfer (FET) cycles after preimplantation genetic testing (PGT) achieve better clinical outcomes? DesignThis retrospective analysis included 3400 vitrified–warmed single blastocyst transfer cycles after PGT from January 2011 to November 2020, and involved 2332 patients with regular menstrual cycles. The decision to proceed with an assisted NC (n = 827) or HRT (n = 2573) before FET was reached based on a combination of patient preference and physician guidance. Clinical pregnancy rate, live birth rate, early miscarriage rate and obstetric outcomes were compared. ResultsNo significant difference was observed between the assisted NC and HRT groups in terms of clinical pregnancy rate (51.6% versus 50.7%, P = 0.634), live birth rate (44.0% versus 43.4%, P = 0.746) or early miscarriage rate (12.6% versus 12.0%, P = 0.707). Multivariate analysis indicated that the endometrial preparation protocol was not an independent factor for a clinical pregnancy or live birth. In the HRT group, the Caesarean section rate (64.7% versus 51.9%, P < 0.001) and pregnancy complication rate (20.2% versus 13.8%, P = 0.003) were significantly higher. The two groups were not statistically different with respect to gestational age, early preterm birth rate, fetal weight or fetal birth defect rate. ConclusionsFor patients undergoing a PGT–FET cycle involving a single blastocyst transfer, using assisted NC and HRT for the endometrial preparation could lead to comparable rates of clinical pregnancy and live birth. Additionally, NC is safer than HRT in terms of avoiding pregnancy complications and adverse obstetric outcomes.

Pregnancy Outcomes After Frozen-Thawed Embryo Transfer in the Absence of a Corpus Luteum.

Background: Nowadays, frozen-thawed embryo transfer (FET) cycles represent a high proportion of fertility treatments worldwide. Recent studies suggest differences in pregnancy outcomes depending on the FET treatment protocol used. The reason for this is still unclear, but the number of corpora lutea (CL) at conception is discussed as a possible factor. This study aims to investigate whether maternal and neonatal outcomes for pregnancies following FET lacking a CL differ from FET with one or more CL in order to explore a potential link between CL absence and adverse pregnancy outcomes.Methods: The study was designed as a retrospective, multi-center observational study with two cohorts after singleton live birth [0 CL cohort (FET in a programmed cycle, n = 114) and ≥ 1 CL cohort (FET in a natural or stimulated cycle, n = 68)]. Participants completed a questionnaire on the outcome of pregnancy and birth records were analyzed in a descriptive way. Multivariable logistic and linear regressions were performed in order to explore associations between CL absence and pregnancy outcomes. The strength of the agreement between the information in the survey and the diagnoses extracted from the files was assessed by Cohen's Kappa.Results: The risk of hypertensive disorders of pregnancy was higher after FET in the absence of a CL compared to FET with CL presence (aOR 5.56, 95% CI 1.12 – 27.72). Birthweights and birthweight percentiles were significantly higher in the 0 CL group. CL absence was a predictor of higher birthweight (adjusted coefficient B 179.74, 95% CI 13.03 – 346.44) and higher birthweight percentiles (adjusted coefficient B 10.23, 95%, 95% CI 2.28 – 18.40) particularly in female newborns of the 0 CL cohort. While the strength of the agreement between the reported information in the survey and the actual diagnoses extracted from the files was good for the majority of outcomes of interest it was fair in terms of hypertension (κ = 0.38).Conclusion: This study supports observations suggesting a potential link between a lack of CL at conception and adverse maternal and neonatal outcomes. Further investigations on causes and pathophysiological relationships are yet to be conducted.

Laser-assisted hatching zona thinning does not improve the pregnancy outcomes of poor-quality blastocysts in frozen-thawed embryo transfer cycle: a retrospective cohort study.

It had been suggested, after facilitating the hatching process, improved pregnancy outcomes could be attained in embryos with thick and hard zona. This study aimed to determine the effect of zona thinning on pregnancy outcomes in poor-quality frozen-thawed blastocysts. This retrospective study included 230 women (≤ 40years) who underwent frozen embryo transfer of poor-quality blastocysts (scored < 3BB). In total, 105 patients were in the assisted hatching group in which the zona was thinned by laser before transfer and 125 patients were in the control group in which the blastocysts were non-manipulated. Patients' demographics, cycle characteristics, and pregnancy outcomes were compared between the assisted hatching group and the control group. Further, regression analysis was applied to test the correlation between assisted hatching and live birth. All parameters in the patients' demographic characteristics and the cycle's characteristics were not significantly different between two groups. As for pregnancy outcomes, thesecond trimester pregnancy loss was significantly higher in the assisted hatching group (P = 0.035). Other pregnancy outcomes, including implantation rate, clinical pregnancy rate, biochemical miscarriage rate, thefirst trimester pregnancy loss, ongoing pregnancy rate, and live birth rate were comparable between two groups. The logistic regression analysis demonstrated no association between live birth and assisted hatching (univariate, OR = 0.787, P > 0.05; multivariate, OR = 0.652, P > 0.05), and the area under the receiver operating characteristic curve of the regression model was almost 0.7. It suggested that zona thinning may not be supposed to perform on poor-quality, frozen-thawed blastocysts. The indications of assisted hatching were still needed to further investigate.

DOES PROLONGED ESTRACE ADMINISTRATION EFFECT ON PREGNANCY OUTCOME IN PROGRAMMED FROZEN EMBRYO TRANSFER CYCLE?

To determine whether women in frozen-thawed embryo transfer (FET) cycles, who continued prolonged estrogen administration beyond the standard 12 days due to a thin endometrial stripe exhibited lower pregnancy rates. We retrospectively analyzed the outcomes of 822 FET cycles from January 1, 2019 through March 1, 2021. Oocyte recipients or women with known intrauterine adhesions were excluded. Women received twelve days of 6 mg of oral 17 beta Estradiol (Estrace) after ovarian suppression was confirmed. If after twelve days of Estrace their endometrial stripe (ES) was equal to or less than 7 mm, then their estrogen regimen was continued until her ES was at least 7mm. Intramuscular progesterone 50mg intramuscularly was then administered and a single thawed blastocyst was transferred 132 hours later. Variables assessed included thickens of endometrium, pregnancy (serum hCG), clinical pregnancy, and implantation rate by fetal cardiac activity and pregnancy outcome. The Fisher’s Exact Test and t-test were used. A p value <0.05 was considered significant. Twenty three of 822 cycle were continued on their estrogen regimen to meet ES criteria for at least five days (range 5 to 14 days). No significant differences in age, prior failed FET cycles, and percentage of euploid blastocysts were noted between those women who did or did not requires at least five days more of exogenous estrogen. However, endometrial thickness was significantly thicker in regular FET group compared that of pushed FET cycle at day 12 (9.59 mm vs 6.16 mm, p<0.05). Furthermore, their thin endometrial thickness was significantly improved after prolonged Estrace (6.16 mm vs 7.49 mm, p<0.05). Among pushed FET cycles, five patients were pushed for 14 days and the endometrial thickness were improved from 4.78 mm to 7.08 mm (p=0.11). The pregnancy rate (positive serum hCG/total transfers), clinical pregnancy rates and implantation rate were not significantly different between regular and pushed FET cycles (73.2 %vs 75.0 %), (68.8 % vs 62.5 %), and (59.4 % vs 52.0 %), respectively. The pregnancy outcomes in two groups were similar by age group or PGT performed group. Additionally, chemical pregnancy loss or miscarriage rate did not differ between two groups (7 % vs 4%) and (7 % vs 4 %), respectively. Ongoing pregnancy/live birth rate was 60.9 % (14/23) for regular FET and 59.7 % (462/799) for pushed FET. Our findings suggest that continued exogenous estrogen administration successfully increased the endometrial thickness in all patients with a thin ES and did not adversely affect pregnancy outcome.

CUMULATIVE CLINICAL PREGNANCY RATES PER OOCYTE RETRIEVAL AFTER IN VITRO FERTILIZATION

To investigate cumulative clinical pregnancy rates (CCPR) and to improve patient counseling with the prognostic pregnancy outcome per oocyte retrieval cycle. DESIGN: Retrospective study. All classical IVF or ICSI Cycles involving fresh embryo transfer carried out between January 2015 and December 2018 at our clinic were investigated, including fresh ET only and fresh ET followed by 1-6 time frozen-thawed embryo transfers (FET). Both fresh ET and FET were included to calculate the CCPR. Clinical pregnancy was confirmed by the observation of a gestational sac with a fetal heartbeat on ultrasound evaluation. Results were analyzed by using chi-square test (P=0.05). This study included 535 fresh ET cycles and 330 FET cycles. The average age of the patients was 35.9 (26-45). The ratio of fresh cycles with frozen embryos after transfer was 75% (402/535). The average number of embryos cryopreserved per cycle was 3.1. The average number of embryos transferred was 1.3. The CCPR per oocyte retrieval increased by each cycle of frozen-thawed embryo transfer (Table 1). The significant differences in CCPR were found among Fresh, FET1 and FET2 cycles. No significant differences in CCPR were observed among FET2, FET3, FET4, FET5 and FET6 cycles.Tabled 1Table 1. The cumulative clinical pregnancy rates per oocyte retrievalCycleClinical pregnancy rateCumulative clinical pregnancy rateFresh42.4% (227/535)42.4% (227/535) aFET146.8% (88/188)58.9% (315/535) bFET243.1% (34/80)65.2% (349/535) cFET342.9% (15/36)68.0% (364/535) cFET46.3% (1/16)68.2% (365/535) cFET537.5% (3/8)68.8% (368/535) cFET650.0% (1//2)69.0% (369/535) ca,b,c Values with different superscript letters within the same column are significant different (p<0.05) Open table in a new tab a,b,c Values with different superscript letters within the same column are significant different (p<0.05) Our data analysis indicated that the CCPR per oocyte retrieval increased until the second FET cycle with no benefit for additional FET cycles to have one pregnancy. The results provided here may be useful in counseling patients on the high pregnancy outcome (69.0%) per oocyte retrieval cycle.

ENDOMETRIOSIS ASSOCIATED WITH A LOWERED CUMULATIVE LIVE BIRTH RATE IN IVF BY COMPROMISING THE QUANTITY AND QUALITY OF EMBRYOS

What is the impact of endometriosis on the cumulative live birth rate (CLBR) among the patients undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment by using fresh plus linked frozen embryo transfer cycles with first conventional stimulation? A retrospective cohort study was carried out by recruiting a total of 3071 patients undergoing IVF/ICSI treatment at the Reproductive Medicine Center of Shenzhen Zhongshan Urology Hospital between January 2012 and December 2014. 436 patients diagnosed as endometriosis by imageological and/or surgical approaches were assigned into the study group to compare with the 2635 subjects with tubal factor infertility in the control group throughout the IVF/ICSI treatment. Measurements for primary outcomes included cumulative live birth rate per initiated cycle, while secondary outcomes were evaluated by the number of retrieved oocytes , metaphase II oocytes, transplantable embryos, good embryos, clinical pregnancy rate, and live birth rate independent in fresh and cryopreserved cycles. Bivariate followed by multivariate logistic regression analysis was conducted, with the differences analyzed by Chi squared test and Student’s t-test as appropriate. The two groups are comparable in clinical pregnancy rate and miscarriages rate in both of the fresh (56.64% vs. 57.03%, p=0.903) (9.49% vs. 13.58%, p=0.153) and the frozen-thawed embryo transfer cycles (47.6% vs. 54.3%, p=0.062) (22.4% vs. 15.3%, p=0.068). However, the live birth rate, though about the same level in the two groups in fresh embryo transfer cycles (47.47% vs. 46.20%, p=0.673), was significantly lower in the endometriosis group in frozen embryo transfer cycles (33.78% vs. 43.74%, p=0.005), thus leading to a declined CLBR with statistical significance (51.83% vs. 60.87%, p < 0.001). The results of Logistic regression analysis also revealed a lower CLBR of the patients with endometriosis. Given that the inter-group differences were present in multiple aspects such as age, AFC, as well as the basal FSH and BMI levels, multivariate Poisson regression was performed aiming to remove the confounders through adjusting these baseline factors, with a result indicating a close association between endometriosis and low CLBR (OR=1.525; 95%CI, 1.123-2.070; p = 0.007). The results from our study suggest that endometriosis is very likely to be associated with a lowered CLBR in IVF by compromising the quantity and quality of embryos, which seems to be more evident in young women with endometriosis. So young infertility patients with endometriosis should actively start ART treatment as soon as possible.

EFFECTS OF SUBENDOMETRIAL AUTOLOGOUS PLATELET RICH PLASMA INJECTION ON ENDOMETRIUM AND PREGNANCY RATES IN PATIENTS WITH UNRESPONSIVE THIN ENDOMETRIUM UNDERGOING FROZEN-THAWED EMBRYO TRANSFER

A receptive endometrium, a viable embryo, and cross-talk between the endometrium and the embryo are essential factors for successful embryo implantation. Endometrial thickness is associated with the outcome of frozen-thawed embryo transfer (FET) cycles, and a thin endometrium refractory to available treatment modalities remains a challenge in contemporary reproductive medicine. Platelet-rich plasma (PRP) is rich in growth factors and cytokines and has been used as an agent that induces tissue regeneration.

DOES THE MOSAIC EMBRYO RATIO OF PGT-A CYCLES IMPACT THE LIVE BIRTH CHANCE EVEN WHEN AN EUPLOID EMBRYO IS TRANSFERRED?

Preimplantation genetic testing for aneuploidy (PGT-A) has the potential to detect mosaicism in trophectoderm biopsies with Next-Generation Sequencing (NGS). Many couples who opted for PGT-A have both euploid and mosaic embryos in their cohort of tested embryos. However, little is known about how live birth outcomes are affected by mosaic embryo ratios of PGT-A tested embryos even though euploid embryos are transferred. This retrospective study was based on 636 PGT-A tested frozen-thawed single euploid embryo transfer cycles of which live birth outcome is known. The inclusion criteria were having at least one euploid and one mosaic embryos. Mosaicism was reported for PGT-A outcomes deviated for 20-80% from 2 chromosome copy number. Mosaic embryo ratio was defined as the number of mosaic embryos divided by the total number of blastocysts tested. This data included embryo transfers between January 2017 and March 2020 in a single ART clinic. PGT-A was done by NGS ReproSeq on IonTorrent S5 (Thermo Fisher) following trophectoderm biopsy. For the categorical data Chi-Square test was used. For continuous variables, Mann-Whitney Test was applied. Pearson correlation coefficient was used for testing how two variables are related to each other. The live birth rate of the study group was 55.8%. When data was evaluated according to the live birth status (+(n=355) or -(n=281)), no significant differences were observed for the number of oocytes collected, mature oocytes, blastocysts, biopsied blastocysts, number of euploid and mosaic embryos per cycle. Female age at the time of transfer and mosaic embryo ratio were statistically significant (p=0.015 and p=0.040, respectively). Female age for women who had reached live-birth was 0.9 years less and mosaic embryo ratio was 2.3% less when compared to women who did not reach live-birth. As only female age and mosaic embryo ratio were found to be statistically significant between the groups, their relationship with each other was tested and found to be inversely correlated, eg. with increasing female age, the mosaic embryo ratio was decreasing (r= -0.07, -0.14 to -0.01 95% CI, p=0.021). The median value for mosaic embryo ratio was 28.6%. When the study group was divided into two with 28.6% as a cut-off, the live birth rate was 10.1% higher for cycles with lower mosaic embryo ratio (62.4% vs 52.3%) (p=0.160). The live-birth rate for euploid FET with at least 1 mosaic embryo was not statistically different when compared to 1193 euploid FET of PGT-A cycles with no mosaic embryo (55.8% vs 55.3%, respectively) (p=0.839). Diverse molecular mechanisms including altered cell cycle checkpoints, aberrations of the centrosome and failed chromatid cohesion are known to contribute to mitotic errors (McCoy, 2017). Although euploid, some embryos from the same PGT-A tested cohort may be affected by the molecular pathways contributing to embryonic mosaicism.

IS HORMONE REPLACEMENT FOR ENDOMETRIAL PREPARATION ASSOCIATED WITH PREGNANCY LOSSES IN FROZEN-THAWED SINGLE-BLASTOCYST TRANSFER CYCLES

To evaluate the rates of pregnancy losses in frozen-thawed embryo transfer (FET) cycles and to investigate whether hormone replacement for endometrial preparation is a risk factor for biochemical or clinical pregnancy losses.

COMPARISON OF TWO VAGINAL PROGESTERONE FORMULATIONS, TABLET (LUTINUS 100mg) AND GEL (CRINONE %8), FOR LUTEAL PHASE SUPPORT IN MODIFIED NATURAL CYCLE FROZEN-THAWED SINGLE BLASTOCYST TRANSFERS

The aim of our study is to evaluate the pregnancy outcomes between the patients using vaginal progesterone tablet (VPtablet) or vaginal progesterone gel (VPgel) in modified natural cycle frozen-thawed embryo transfers (mNC-FETs)

Effect of endometrial preparation protocols on the risk of ectopic pregnancy for frozen embryo transfer

Studies have consistently reported a significantly reduced incidence of ectopic pregnancy (EP) for frozen-thawed embryo transfer (ET) cycles compared with fresh cycles. However, only a few studies reported an association between endometrial preparation protocols on EP and results were conflicting. A registry-based retrospective cohort study of 153,354 clinical pregnancies following frozen single ETs between 2014 and 2017 were conducted, of which 792 cases of EP (0.52%) were reported. Blastocyst embryo transfers accounted for 87% of the total sample and were significantly associated with a decreased risk for EP compared with early cleavage ET (0.90% vs. 0.46%, adjusted OR = 0.50, 95% CI, 0.41 to 0.60). Compared with natural cycles, hormone replacement cycles (HRC) demonstrated a similar risk for EP (0.53% vs. 0.47%, adjusted OR = 1.12, 95% CI, 0.89 to 1.42). Subgroup analysis with or without tubal factor infertility and early cleavage/blastocyst ETs demonstrated similar non-significant associations. Endometrial preparation protocols using clomiphene (CC) were associated with a significantly increased risk for EP (1.12%, adjusted OR = 2.34; 95% CI, 1.38 to 3.98). These findings suggest that HRC and natural cycles had a similar risk for EP. Endometrial preparation using CC was associated with an increased risk of EP in frozen embryo transfer cycles.

Immediate versus delayed frozen embryo transfer in women following a failed IVF-ET attempt: a multicenter randomized controlled trial

BackgroundThe optimal time at which to perform a frozen-thawed embryo transfer (FET) following a failed in-vitro fertilization-embryo transfer (IVF-ET) attempt remains elusive to most reproductive experts. Physicians often delay the introduction of FET due to concerns related to potential residual effects of ovarian hyperstimulation which may interfere with the regular menstrual cycle. Moreover, given that most of the published studies on the topic are retrospective and have inconsistent findings, it is crucial to develop evidence-based randomized control guides for clinical practice. Therefore, this well-designed randomized controlled trial (RCT) was conducted to determine whether it is necessary to delay FET for at least one menstrual cycle after the failure of fresh embryo transfer.MethodsInfertile women eligible for IVF-ET were invited to participate in this multicenter, randomized, non-inferiority, parallel-group, unblinded, controlled trial at the academic fertility centers of four public hospitals in Chinese Mainland. Infertile women scheduled to receive their first FET cycle after a failed IVF-ET attempt were randomly assigned to either (a) the immediate FET group in which FET was performed in the first menstrual cycle following the failed IVF-ET cycle (n = 366) or (b) the delayed FET group in which FET was performed in the second or subsequent menstrual cycle following the failed IVF-ET cycle (n = 366). All FET cycles were performed during hormone replacement cycles for endometrial preparation. The primary outcome was the ongoing pregnancy, defined as a detectable fetal heart beat beyond twelve weeks of gestation. Secondary outcomes were other pregnancy-related outcomes, maternal and neonatal complications. Analysis was performed by both intention-to-treat and per-protocol principles.ResultsA total of 646 FETs were completed. The frequency of moderate to severe depression and high stress level prior to FET in delayed FET group were significantly higher than that in immediate FET group (10.6% vs 6.1%, p = 0.039; 30.3% vs 22.4%, p = 0.022, respectively). Immediate FET resulted in a higher frequency of clinical pregnancy than did delayed FET (41.7% vs 34.1%), for a relative risk (RR) of 1.23 (95% confidence interval [CI], 1.00–1.50; p = 0.045). Women who underwent immediate FET also had a lower frequency of biochemical pregnancy loss (11.7% vs. 30.6%), with a RR of 0.28 (95% CI 0.23–0.63, p < 0.001), and a higher frequency of embryo implantation (25.2% vs. 20.2%), with a RR of 1.25 (95% CI 1.01–1.53; p = 0.038). Although the ongoing pregnancy and live birth rates did not differ significantly between the immediate FET and delayed FET groups (37.1% vs 30.3%, RR 1.22, 95% CI 0.99–1.52, p = 0.067; 36.5% vs 30.0%, RR 1.22, 95% CI 0.98–1.52, p = 0.079, respectively), a multivariate logistic regression analysis adjusted for potential confounders such as depression and stress levels revealed that the immediate FET group had a significantly higher ongoing pregnancy and live birth rates than the delayed FET group (odds ratio 0.68, 95% CI 0.47–0.99, p = 0.041; odds ratio 0.67, 95% CI 0.46–0.96, p = 0.031). The risks of maternal and neonatal complications were comparable between the two groups.ConclusionsIn women with a previous failed IVF-ET attempt, immediate FET resulted in higher ongoing pregnancy and live birth rates than delayed FET. These findings warrant caution in the indiscriminate application of a delayed FET strategy when apparent risk of high stress level is perceived.Trial registrationChiCTR2000033313.

Low Antimullerian Hormone Levels Improve Fertility Outcome in Patients with Polycystic Ovary Syndrome

Background: It was known that polycystic ovary syndrome (PCOS) patients have high AMH levels. The aim of this study is to show whether low AMH levels are associated with better clinical pregnancy rates in patients with PCOS. Methods: This retrospective study was performed on 443 patients with PCOS referred to BAU MedicalparkGoztepe Hospital IVF Clinic from January 2015 to October 2020. Participants ranged in age from 18 to 40, had their first two IVF trials, had performed frozen-thawed embryo transfer (FET) cycle at day 5. The diagnosis of PCOS was made using the Rotterdam criteria. Data related to patients' AMH were compared with each other, and based on the value, participants were divided into two groups: the first group was AMH≥7 (N = 49); The second group was AMH &lt;7 (N = 394). Results: The pregnancy test was positive for 288 (65%) participants. Of these participants, 214 had livebirth, 71 had miscarriages, and 3 had stillbirths. There was no significant difference in age and BMI between the two groups. There were no significant differences between the two groups in the number of stimulation days, the total number of oocytes, and MII oocytes. The numbers of frozen embryos were higher in the AMH≥7 group (p = 0.005). The positive pregnancy results were significantly higher in the AMH&lt;7 group than in the AMH≥ 7 group (P= 0.02). There was no significant difference in live birth, stillbirth, and miscarriage rates between the two groups. Conclusion: Low levels of circulating AMH are associated with better clinical pregnancy rates in patients with PCOS.

Association between endogenous LH level prior to progesterone administration and live birth rate in artificial frozen-thawed blastocyst transfer cycles of ovulatory women.

Is there an association between serum LH levels prior to progesterone administration and live birth rate (LBR) in artificial frozen-thawed embryo transfer (FET) cycles? : Low serum LH levels on the day before progesterone initiation in artificial frozen-thawed blastocyst transfer cycles of ovulatory women are associated with a lower LBR. In artificial FET cycles, exogenous oestrogen and progesterone are administered sequentially to mimic the serum hormone pattern similar to the natural cycle. In oestrogen-only phase, the supplemental oestrogen causes thickening of the endometrium and is sometimes accompanied by a rise in serum LH. However, whether the endogenous LH level in artificial FET cycles is related to clinical outcomes remains unclear. A retrospective cohort study including 3469 artificial frozen-thawed blastocyst transfer cycles was conducted at a tertiary-care academic medical centre between February 2014 and January 2020. A total of 3469 frozen blastocyst transfer cycles were stratified into four groups based on the quartiles of serum LH level before progesterone initiation: <25th percentile (LH < 8.79 mIU/ml), 25-50th percentile (8.79 ≤ LH ≤ 13.91 mIU/ml), 51-75th percentile (13.91 < LH ≤ 20.75 mIU/ml) and >75th percentile (LH > 20.75 mIU/ml). The serum LH level >75th percentile group was considered as the reference group. Patients with polycystic ovarian syndrome or other ovulatory disorders were excluded from the study. We also excluded cycles with an endometrial thickness <7 mm before progesterone initiation and patients with intrauterine adhesions and uterine abnormalities. In order to avoid the interference of BMI, all patients were divided into two categories based on the overweight threshold: BMI <25 kg/m2 and ≥25 kg/m2, and the impacts of serum LH levels on LBR were investigated separately. Univariable and multivariable logistic regression analysis were performed to adjust for potential confounders. EmpowerStats software and R-project were used to build smooth curve fitting models. Compared with the reference group, the implantation rate significantly decreased with low LH levels (<25th percentile) on the day before progesterone initiation (odds ratio [OR] = 0.74; 95% CI, 0.64-0.86; P = 0.001). Accounting for major covariates, low LH levels were associated with a relatively lower LBR (adjusted OR = 0.649; 95% CI, 0.531-0.794; P < 0.001), mainly due to a lower implantation rate, lower clinical pregnancy rate and higher pregnancy loss rate. Moreover, in the patients with BMI <25 kg/m2, low LH was associated with a lower LBR (P < 0.001); while in the overweight subgroup, LBR and LH were not correlated (P = 0.823). The main limitation of this study is its retrospective design. Owing to the relatively small number in the overweight group, the results of the overweight subgroup should be interpreted with caution. The evidence provided in this study shows the importance of serum LH levels on the day before progesterone initiation in patients undergoing artificial FET cycles. Hypothalamic dysfunction may be one of the important causes of a relatively low LH, which is related to impaired pregnancy outcomes. Serum LH levels may be used as one of the clinical indicators to predict pregnancy outcomes. No funding and no competing interest were involved in this study. NA.

Long-term pituitary downregulation before frozen embryo transfer improves clinical outcomes in women positive for serum autoantibodies

ObjectiveAutoantibodies are associated with worse outcomes in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI), including increasing miscarriage rate, lowering pregnancy rate, and lowering delivery rate. However, little is known about improving IVF/ICSI outcomes for autoantibody-positive women, especially in frozen-thawed embryo transfer (FET) cycles. This study aimed to investigate whether pituitary suppression before FET improves the clinical pregnancy rate (CPR) and live birth rate (LBR) for IVF/ICSI women positive for serum autoantibodies. Study designA total of 181 infertile women positive for serum autoantibodies were recruited, including 65 women receiving GnRHa and hormone replacement therapy protocols (G-HRT group) and 116 women using modified natural cycles (MNC)/mild stimulated cycles (MSC) as FET protocols (MNC/MSC group). The outcomes were compared between two groups, including CPR, implantation rate (IR), miscarriage rate (MR), ongoing pregnancy rate (OPR), LBR, and gestational age (GA). The primary outcome of the study was CPR. ResultsCPR, OPR, and LBR per embryo transferred in the G-HRT groups were significantly higher than those in the MNC/MSC group. No statistically significant differences were observed in the IR and MR. The CPR, IR, MR, OPR, and LBR was 72.23%, 64.00%, 12.77%, 63.07%, and 63.07% in the G-HRT group, respectively, while that was 56.90%, 53.07%, 10.60%, 50.00%, and 50.00% in the MNC/MSC group, respectively. After adjusting for partial potential confounding factors using multiple logistic regression, the type of endometrial preparation is the factor independently associated with enhanced CPR (OR = 0.48, 95%CI: 0.24–0.96, P = 0.039). ConclusionsThe current study showed that prior long-term GnRHa suppression could benefit patients with high serum autoantibody levels during IVF/ICSI FET cycles.

Analysis of factors affecting live birth outcome of frozen-thawed embryo transfer cycle

Objective: To analyze the related factors affecting the success of frozen-thawed embryo transfer (FET). Methods: A total of 563 couples treated in the Reproductive Medicine Center of Guangdong Hospital of Traditional Chinese Medicine from January 2017 to March 2020 were selected as subjects. A total of 736 FET cycles were included to analyze the live birth outcomes of FET. Pregnancy outcomes, pregnancy complications and embryo status of patients between the live birth group and the non-live birth group were compared. A multivariate logistic regression model was used to evaluate the association between the 15 candidate factors and live birth outcomes for identifying independent factors associated with the live birth outcomes of the FET. Results: Among the enrolled subjects, the men were (33±5) years old at sperm extraction while the women were (31±4) years old at ovum pick-up (OPU) and (32±4) years old at embryo transfer (ET) and their infertility duration were (3.5±2.6) years. There were 333 (45.2%) live birth cycles and 403 (54.8%) non-live birth cycles in the 736 FET cycles. Pregnancy complications occurred in 49 cases (14.7%) of the live birth group. The age of the women at ET ((31±4) vs (32±4) years), the age of the women at OPU ((30±4) vs (32±4) years) and the age of the men at sperm extraction ((33±4) vs (34±5) years) in the live birth group were all lower than those in the non-live birth group. The infertility duration was shorter ((3.2±2.2) vs (3.6±2.8) years), and the proportion of primary infertility was higher ((63.1%, 210 cases) vs (49.6%, 200 cases)) in the live birth group (P<0.05) than those in the non-live birth group. Multivariate logistic regression analyses showed that the age of woman at ET (OR (95%CI): 0.50 (0.27-0.92), P=0.026), the types of infertility (0.62 (0.43-0.88), P=0.008), the numbers of optimal embryos transferred (1.60(1.11-2.31), P=0.012), and the types of embryos transferred (2.43 (1.46-4.01), P=0.001) were statistically significant related factors for live birth outcome of FET. Conclusion: The age of the woman at ET, the types of infertility, the numbers of optimal embryos transferred and the types of embryos transferred are associated factors for the outcomes of live birth after FET.

The effect of LH rise during artificial frozen-thawed embryo transfer (FET) cycles.

PurposeTo evaluate the association between a rise in serum luteinizing hormone (LH) levels during artificial frozen–thawed embryo transfer (FET) cycles and clinical pregnancy rate.MethodsA retrospective cohort study of women undergoing artificial FET cycles. We compared cycles in which LH double itself from the early follicular phase and further (group A) to cycles without a rise in LH (group B). Endometrium preparation was achieved by administration of 2 mg three times per day estradiol valerate tablets. Embryo transfer (ET) was conducted after achieving endometrial thickness > 7 mm and vaginal progesterone was added according to the embryo’s age. A beta-hCG was measured 13–14 days after ET. Clinical pregnancy was diagnosed on transvaginal ultrasound.ResultsData from 984-FET cycles were retrieved. LH, exogenous estradiol (E2), progesterone values, endometrial thickness, and pregnancy outcomes were available in all patients. From 984-FET cycles, 629 (63.9%) had a doubling, and 355 (36.07%) had no rise in LH. Patients mean age was 30 years, similar in both groups. A multivariable logistic regression analysis was calculated to assess the effect of LH rise and pregnancy outcomes, after adjusting for confounders including a rise in E2 level and endometrial thickness. In this model, there was no association between doubling LH values and pregnancy rates (adjusted odds ratio: 1.06, 95% CI: 0.75–1.5, P = 0.74).ConclusionLH rise during artificial FET cycles does not alter pregnancy rates. Apparently, hormonal monitoring of LH levels may not yield useful information in the artificial FET cycle and may be omitted.Lay summarySupplementation of estradiol, a hormone produced by the ovaries, starting at the beginning of the menstrual cycle of an artificially frozen embryo transfer (FET) can lead to a rise in luteinizing hormone (LH), the hormone that induces ovulation. Such a rise in LH may interfere with embryo implantation, the process where the embryo attaches to the inner lining of the uterus and, therefore, could affect the chances of pregnancy. The current study is the first to assess the effect of a dynamic rise in LH levels during FET cycles on pregnancy rates. This study found no difference in pregnancy rates between FET cycles where the LH doubled compared to cycles without such a rise in LH. Larger, prospective studies should be conducted to assess the impact of LH elevation on pregnancy outcomes.

Endometrial compaction is associated with the increased live birth rate in artificial frozen-thawed embryo transfer cycles

We aimed to assess the effect of endometrial compaction on the live birth rate in frozen-thawed embryo transfer (FET) cycles and to investigate the parameters associated with compaction. FET cycles performed in a tertiary care infertility centre between May 2013 and October 2019 were reviewed retrospectively. The decremental change of endometrial thickness between the end of oestrogen phase and ET day was defined as endometrial compaction. The primary outcome measure was endometrial compaction, and the secondary outcome was the live birth rate. Among all, 89 had endometrial compaction and 194 did not. The live birth rate was significantly higher in the compaction group (23.6 vs. 13.4%, respectively; p = 0.039). Multivariate logistic regression analysis revealed that in FET cycles with artificial endometrial preparation, the chance for live birth was significantly higher in cycles with endometrial compaction [OR: 3.133, 95% confidence interval (CI) 1.104–8.892; p = 0.032] when adjusted for age, stage of the embryo, and endometrial thickness at the end of the oestrogen phase. According to receiver operating characteristic (ROC) curve analysis the sensitivity and specificity of 9.25 mm endometrial thickness at the end of oestrogen phase were 76.4 and 58.8%, respectively (area under the curve: 0.701, 95% CI 0.640–0.763; p < 0.001) to predict endometrial compaction.

Oocyte Degeneration After ICSI Is Not an Indicator of Live Birth in Young Women.

IntroductionIntracytoplasmic sperm injection (ICSI) was introduced in 1990s as one of the most dramatic breakthroughs in assisted reproductive technology. Even with advances in ICSI technology, this mechanical micromanipulation carries a 5 to 19% risk of oocyte degeneration. Whether the presence of oocyte degeneration reflects the sibling oocyte quality and predicts the sibling embryo development potential and clinical pregnancy outcomes remains controversial. There is no study showing the competence of the sibling embryos from the prospective of cumulative live birth rate. Whether oocyte degeneration is associated with poor quality of the remainder of the cohort remains further to be elucidated.MethodThis retrospective observational study included a total of 488 OPU cycles underwent ICSI with fresh cleavage stage embryo transfer and successive frozen/thawed embryo transfer (FET) cycles from January 2018 to December 2019. All female patients were under the age of 35 years, and underwent ICSI with or without oocyte degeneration (OD). Cycles with at least one oocyte degenerated were defined as oocyte degeneration group (OD group), and cycles with no oocyte degenerated were defined as non-OD group. The OD group was further divided to three subgroups according to different oocyte degeneration rate (<10%, 10-20%, and >20%).ResultsThere were no significant differences with regards to implantation rate (38.5% vs 35.1%, P=0.302), clinical pregnancy rate (54.9% vs 50.3%, P=0.340), and LBR per OPU cycle (47.0% vs 42.9%, P=0.395) between OD and non-OD groups. Initial gonadotropin dosage, E2 level on hCG day and the number of matured oocytes appeared to be independent risk factors for OD. The adjusted odds ratio of live birth rate per OPU cycle were similar in different oocyte degeneration rate subgroups. The ongoing pregnancy/LBR per transfer in FET cycles was not significantly different between OD group and non-OD groups (38.8% vs 43.9%, P=0.439). The cumulative LBR per OPU cycle was also comparable between OD and non-OD group (63.4% vs 64.8%, P=0.760).ConclusionThe results provide cycle-based evidence that the presence of oocyte degeneration after ICSI is not an indicator for predicting the cumulative live birth rate per OPU cycle in young women.

Impact of preimplantation genetic testing on obstetric and neonatal outcomes: a systematic review and meta-analysis

To investigate whether preimplantation genetic testing (PGT) increases the risk of adverse obstetric and neonatal outcomes. Systematic review and meta-analysis. Not applicable. Pregnancies achieved after PGT or invitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Systematic search of databases until December 2020 with cross-checking of references from relevant articles in English. Obstetric and neonatal outcomes after PGT and IVF/ICSI, including mean birth weight, low birth weight, very low birth weight (VLBW), mean gestational age at birth, preterm birth, very preterm birth, birth defects, intrauterine growth retardation (IUGR), sex ratio, cesarean section, hypertensive disorders of pregnancy, gestational diabetes mellitus, placenta disorder (placenta previa, placenta abruption, placenta accreta), and preterm premature rupture of membranes. Ultimately, a total of 785,445 participants were enrolled in this meta-analysis, and these participants were divided into a PGT group (n = 54,294) and an IVF/ICSI group (n = 731,151). The PGT pregnancies had lower rates of low birth weight (risk ratio [RR] 0.85, 95% confidence interval [CI] 0.75 to 0.98), VLBW (RR 0.52, 95% CI 0.33 to 0.81), and very preterm births (RR 0.55, 95% CI 0.42 to 0.70) than those of IVF/ICSI pregnancies. However, the PGT group had a higher rate of the obstetric outcome of hypertensive disorders of pregnancy (RR 1.30, 95% CI 1.08 to 1.57). The PGT did not increase the risk of other adverse obstetric and neonatal outcomes, such as those associated with mean birth weight, mean gestational age at birth, birth defects, IUGR, sex ratio, cesarean section, gestational diabetes mellitus, placental disorder (placenta previa, placenta abruption, placenta accreta), or preterm premature rupture of membranes. We performed subgroup analysis with only blastocyst biopsies and found that PGT with blastocyst biopsies was associated with a lower rate of VLBW (RR 0.55, 95% CI 0.31 to 0.95). The PGT with blastocyst biopsies did not increase the risk of other adverse obstetric and neonatal outcomes. Additionally, we performed subgroup analysis with only frozen-thawed embryo transfer cycles, and we found that PGT pregnancies were associated with a lower rate of VLBW (RR 0.55, 95% CI 0.31 to 0.97), a lower rate of cesarean birth (RR 0.90, 95% CI 0.82 to 0.99), a higher rate of preterm birth (RR 1.10, 95% CI 1.02 to 1.18), and a higher rate of IUGR (RR 1.21, 95% CI 1.06 to 1.38) than those of IVF/ICSI pregnancies. The PGT with frozen-thawed embryo transfer did not increase the risk of other adverse obstetric and neonatal outcomes. The pooled analysis suggested that PGT did not increase the risk of adverse obstetric outcomes. The association between PGT and a higher risk of IUGR requires further investigation.