Comparable clinical outcomes and live births after single vitrified–warmed and fresh blastocyst transfer

Selective single-blastocyst transfer (SBT) in fresh cycles has been effective in reducing multiple pregnancies. However, we do not know whether this successful strategy of fresh transfer cycles is suitable for cryopreserved cycles. The present study was undertaken to evaluate the feasibility and value of SBT in vitrified–warmed cycles. Clinical pregnancy rate (CPR) was similar with vitrified and fresh SBT (46.61% versus 52.15% respectively). Of the pregnant patients, monozygotic twin, miscarriage and ectopic pregnancy rates were similar with vitrified and fresh SBT. For the newborns, no significant difference was observed in live birth, low birthweight, premature delivery and birth defects rates between vitrified and fresh SBT. With respect to the quality of transferred blastocysts (from BB to AA), a similar CPR and miscarriage rate was obtained for both vitrified and fresh SBT when a similar blastocyst cohort graded ?3BB was transferred. The data show that vitrified SBT is an effective means of reducing multiple pregnancy and that comparable clinical outcomes and live births are achieved if single blastocysts graded ?3BB are transferred for both vitrified and fresh SBT. These data should encourage clinics to evaluate their embryo transfer policy and adopt vitrified SBT as everyday practice.Selective single-blastocyst transfer in fresh cycles has been an effective method to reduce the multiple pregnancies. However, due to a lack of adequate studies, we do not know whether this successful strategy in fresh transfer cycles is suitable in cryopreserved cycles. The present study was undertaken to explore the feasibility and value of single-blastocyst transfer in vitrified–warmed cycles. We found that single-blastocyst transfer in vitrified–warmed cycles is an effective means of reducing multiple pregnancy, and comparable clinical outcomes and live births were achieved if single blastocysts graded ?3BB were transferred for both vitrified–warmed and fresh blastocyst transfer. These data should encourage clinics to evaluate their embryo transfer policy and adopt single-blastocyst transfer in cryopreserved cycles as their everyday practice.     

Pregnancy and live birth following the transfer of vitrified–warmed blastocysts derived from zona- and corona-cell-free oocytes

This study reports two clinical pregnancies and one live birth following the transfer of vitrified blastocysts developed from oocytes with neither zona pellucida nor corona cells. Two zona-free oocytes obtained from two patients of advanced maternal age undergoing minimal stimulation were normally fertilized after intracytoplasmic sperm injection. In case 1, all four blastomeres of the zona-free embryo were loosely associated and inserted back into ruptured zona on day 2. Zona-free embryo from case 2 had tight contacts between blastomeres and was cultured without zona. Both embryos derived from zona-free oocytes progressed to blastocyst stage and were cryopreserved by vitrification. When patients came back for a cryopreserved embryo transfer, both vitrified blastocysts survived warming. In case 1, transfer of a warmed blastocyst with reconstructed zona resulted in a clinical pregnancy that ended in a spontaneous abortion at 22 weeks. In case 2, live birth was achieved with a normal healthy baby (male) weighing 2381 g at 40 weeks’ gestation. This report emphasizes the importance of maintenance of normal cell arrangement on the subsequent embryonic development for a zona-free oocyte. Zona-free oocytes may provide a valuable source of embryos for infertility patients, especially for those with a limited number of oocytes.In this study, we report two clinical pregnancies and one live birth following the transfer of vitrified blastocysts developed from oocytes with neither zona pellucida nor corona cells. Two zona-free oocytes obtained from two patients of advanced maternal age undergoing minimal stimulation were normally fertilized after intracytoplasmic sperm injection. In case 1, all four blastomeres of the zona-free embryo were loosely associated and inserted back into ruptured zona on day 2. Zona-free embryo from case 2 had tight contacts between blastomeres and was cultured without zona. Both embryos derived from zona-free oocytes progressed to blastocyst stage and were cryopreserved by vitrification. When patients came back for a cryopreserved embryo transfer, both vitrified blastocysts survived warming. In case 1, transfer of a warmed blastocyst with reconstructed zona resulted in a clinical pregnancy that ended in a spontaneous abortion at 22 weeks. In case 2, live birth was achieved with a normal healthy baby (male) weighing 2381 g at 40 weeks’ gestation. Our report emphasizes the importance of maintenance of normal cell arrangement on the subsequent embryonic development for a zona-free oocyte. Zona-free oocytes may provide a valuable source of embryos for infertility patients, especially for those with a limited number of oocytes.     

Effect of embryo transfer difficulty on live birth rates studied in vitrified–warmed euploid blastocyst transfers

Research questionThe aim of this study was to investigate the relationship between the different manoeuvres employed or degrees of difficulty during embryo transfer and live birth rate (LBR) in frozen euploid (blastocyst) embryo transfer (FEET).DesignA retrospective, observational study of women undergoing FEET was performed. If the catheter encountered any resistance in its passage through the cervix, a stepwise approach was used. Easy embryo transfer was defined as a direct embryo transfer or use of the outer sheath of the catheter. Difficult embryo transfer was defined as when the process required the use of a Wallace Malleable Stylet (Smiths Medical International Ltd., UK) without or with additional instrumentation such as a tenaculum or uterine sound.ResultsThe analysis involved 370 FEET. LBR was significantly lower in difficult FEET procedures compared with easy ones (54.5% versus 40.5%, P = 0.026) but significance was lost after adjustment for confounders. Use of the outer sheath use did not affect LBR. Although LBR was significantly lower when the stylet, without or with a tenaculum, was required (odds ratio [OR] 0.56, 95% confidence interval [CI] 0.34–0.93; P < 0.05), no statistically significant reduction was observed after adjustment for confounders (OR 0.81, 95% CI 0.45–1.47).ConclusionsNo significant reduction in LBR was observed after adjustment for confounders between difficult and easy FEET, or when use of stylet without or with a tenaculum was required for embryo transfer. The lack of significance may be due to factors such as the sample size or the use of array comparative genomic hybridization analysis. Further studies are needed to confirm these results.     

The impact of serum oestradiol concentration prior to progesterone administration on live birth rate in single vitrified–warmed blastocyst transfer cycles

Research questionCan serum oestradiol concentrations on the day of progesterone initiation predict live birth rates in single, autologous vitrified–warmed blastocyst transfers following artificial endometrial preparation?DesignThis retrospective study included the first transfers of 468 patients with unexplained or tubal factor infertility who underwent freeze-all cycles using single, top-quality blastocysts after artificial endometrial preparation from January 2015 to January 2018. Patients were stratified into four groups based on serum oestradiol concentration percentiles on the day of progesterone initiation: Group 1 (<25th percentile), Group 2 (25–50th percentile), Group 3 (51–75th percentile) and Group 4 (>75th percentile). The primary outcome was live birth rate. The secondary outcomes were implantation, clinical pregnancy and multiple pregnancy rates. Receiver operating characteristic (ROC) curves were generated to evaluate serum oestradiol concentrations in predicting implantation, clinical pregnancy and live birth.ResultsSimilar live birth rates of 51.6%, 55.1%, 54.9% and 56.4% for Groups 1, 2, 3 and 4, respectively, were found. The groups also showed similar implantation and clinical pregnancy rates. ROC analysis revealed that serum oestradiol concentrations on the day of progesterone initiation were not predictive for implantation (area under the curve [AUC] 0.490, 95% CI 0.445–0.554), clinical pregnancy (AUC 0.507, 95% CI 0.453–0.561) or live birth (AUC 0.514, 95% CI 0.461–0.566).ConclusionsSerum oestradiol concentration monitoring just prior to progesterone administration does not appear to be predictive for live birth rates in good prognosis patients undergoing single, autologous vitrified–warmed blastocyst transfer after artificial endometrial preparation. Therefore, the current practice of monitoring serum oestradiol concentration is not supported by this study.     

Association between the number of oocytes retrieved and cumulative live birth rate in women aged 35–40 years undergoing long GnRH agonist IVF/ICSI cycles

Purpose

To study the association between the numbers of oocytes retrieved and the cumulative live birth rates (LBR) in women aged 35–40 years undergoing long GnRH agonist IVF/ICSI cycles.

Methods

A total of 931 women aged 35–40 years who underwent their first cycle of IVF/ICSI treatment between January 2010 and December 2013 at Nanjing Drum Tower Hospital were identified and reviewed. The main endpoint of this study was the cumulative LBR after one complete oocyte retrieval, which included fresh and all subsequent frozen–thaw embryo transfer cycles. Odds ratios (OR) and 95% confidence interval (CI) for live birth were estimated by multivariate logistic regression analysis. Furthermore, all the women were divided into four groups based on the number of oocytes retrieved: 0–4, 5–9, 10–14 or ≥15 oocytes group. Variables were then compared among groups.

Results

We found that 634 out of the 931 patients (68.1%) achieved at least one live birth. The number of oocytes retrieved was an independent predictive factor for live birth, with OR 1.20 (95% CI 1.15–1.26) when adjusted for age (years), duration of infertility and Gn (gonadotrophin) doses. The cumulative LBR in the four different oocyte groups was 35.6, 68.8, 83.4 and 89.2%, respectively. When the 1–4 oocytes group was issued as a reference, the ORs for cumulative LBR gradually increased to 3.66, 6.74 and 11.77 in other three oocytes groups, respectively. The moderate–severe ovarian hyperstimulation syndrome (OHSS) rate was dramatically increased in the ≥15 oocytes group (6.9%) when compared to that in the 10–14 oocytes group (0.8%), while the cumulative LBR only increased 5.8% (from 83.4 to 89.2%).

Conclusions

The ideal number of oocytes retrieved in women aged 35–40 years is 10–14 oocytes, which achieves a high cumulative LBR while maintaining an acceptable low OHSS rate.

     

Effect of pretreatment with a levonorgestrel-releasing intrauterine system on IVF and vitrified–warmed embryo transfer outcomes in women with adenomyosis

Research questionDoes the use of a levonorgestrel-releasing intrauterine system (LNG-IUS) improve the ongoing pregnancy rate of vitrified–warmed embryo transfer in women with adenomyosis undergoing IVF?DesignThis retrospective study included 358 women with adenomyosis undergoing IVF. Of these, 134 women were enrolled in the LNG-IUS group and another 224 women were in the control group. All women were screened for adenomyosis by transvaginal ultrasound and magnetic resonance imaging (MRI). There was no significant difference in the ages of women, FSH, cause of infertility, body mass index, total dose of gonadotrophin used and number of oocytes collected between the two groups. All comparisons performed were between patients undergoing vitrified–warmed embryo transfer.ResultsStatistical differences were found in the ongoing pregnancy rates (41.8% vs 29.5%, P = 0.017) between the LNG-IUS group and control group. Logistic regression analysis showed that the odds ratio (OR) of ongoing pregnancy was significantly increased with LNG-IUS usage (adjusted OR = 1.628, 95% confidence interval 1.011–2.622). Also, differences were found in implantation rates (32.1% vs 22.1%, P = 0.005) and clinical pregnancy rates (44% versus 33.5%, P = 0.045) between the LNG-IUS group and control group.ConclusionsThe results of this study offer some support for evaluating the effect of pretreatment with LNG-IUS in women with adenomyosis in future randomized controlled trials.     

Do trained reproductive endocrinologists perform better than their trainees? Comparing clinical pregnancy rates and live birth rates after transfer of single fresh blastocysts

Purpose

To compare clinical pregnancy rates and live birth rates of single blastocyst transfers performed by attending physicians or fellows in reproductive endocrinology and infertility program.

Methods

Retrospective study in an academic reproductive center. We evaluated 932 fresh single blastocyst transfer cycles performed by fellows in training (389 embryo transfers) and by attending physicians (543 embryo transfers).

Results

There were no differences in the baseline characteristics and IVF cycle parameters between patients who had transfers performed by fellows or attending physicians. Transfers performed by attending physicians or fellows resulted in similar CPR (46.5 vs. 42.9%, p?=?0.28) and LBR (38.3 vs. 34.2%, p?=?0.11). Multivariate logistic regression analysis showed that even after adjusting for possible confounders (age, gravity, parity, baseline FSH, antral follicle count, dose of gonadotropins, stimulation protocol, and quality of embryo transferred), CPR (OR 0.81, CI 0.62–1.07) and LBR (OR 0.79, CI 0.6–1.05) in the two groups were comparable.

Conclusion

Clinical pregnancy rate and live birth rate after embryo transfer performed by attending staffs or fellows are comparable. This finding reassures fellowship programs that allowing fellows to perform embryo transfers does not compromise the outcome.

     

The effect of chromosomal polymorphisms on the outcomes of fresh IVF/ICSI–ET cycles in a Chinese population

Purpose

Chromosomal polymorphisms (CPs) have been reported to be associated with infertility; however, their effects on the outcomes of in vitro fertilization/intracytoplasmic sperm injection–embryo transfer (IVF/ICSI–ET) are still controversial. In this retrospective study, we aimed to evaluate the effect of CPs on IVF/ICSI–ET outcomes.

Methods

To investigate whether CPs affected the outcomes of fresh IVF/ICSI–ET cycles in a Chinese population, we evaluated infertile couples with male carriers of CPs (n?=?348), infertile couples with female carriers (n?=?99), and unaffected couples (n?=?400) who had received their first treatment cycles in our hospital between January 2013 and March 2015.

Results

CPs in either male or female carriers seemed to have adverse effects on IVF/ICSI–ET outcomes. CPs in male carriers affected outcomes mainly by decreasing the rates of fertilization, embryo cleavage, good quality embryos, clinical pregnancies, ongoing pregnancies, and deliveries as well as increasing the biochemical pregnancy rate (P?<?0.05); CPs in female carriers affected outcomes only by lowering the embryo cleavage rate (P?<?0.05). The mean fertilization rate of couples with male CP carriers undergoing IVF was significantly lower than that in those undergoing ICSI (61.1 versus 66.5 %, respectively; P?=?0.0004).

Conclusions

Our data provide evidence for the involvement of CPs in the poor outcomes of fresh IVF/ICSI–ET cycles in a Chinese population. The use of ICSI might improve outcomes by increasing the fertilization rate for men with CPs.

     

Day 3 ET,single blastocyst transfer (SBT) or frozen-thawed embryo transfer (FET): which is preferable for high responder patients in IVF/ICSI cycles?

Purpose

To compare the clinical outcomes after day 3 embryo transfer, day 5 single blastocyst transfer (SBT) and frozen-thawed embryo transfer (FET) in high responder patients (>15 retrieved oocytes) undergoing IVF/ICSI treatment.

Methods

A retrospective analysis of three embryo transfer strategies for the high responder patients in IVF/ICSI cycles. The 1041 high responder patients diagnosed as primary infertility with more than 15 oocytes retrieved were recruited in Day 3 ET group, 308 patients with more than 15 oocytes retrieved first transferred with one blastocyst in SBT group and 425 patients with more than 15 oocytes retrieved in fresh cycle, first transferred with one frozen-thawed blastocyst were assigned in FET group.

Results

In the high responder patients, the clinical pregnancy rate after day 5 SBT was significantly lower than that of day 3 ET (43.18 % VS 57.16 %, p < 0.05). In addition, the clinical pregnant rate and implantation rate of FET cycles were significantly higher than SBT cycles (59.06 % vs. 43.18 % and 64.70 % vs. 47.40 %, p < 0.05). The multiple pregnancy rate in FET cycles was markedly lower than that of day 3 ET (2.35 % VS 34.97 %, p < 0.05).

Conclusions

FET was the preferable strategy for the high responder patients in IVF/ICSI cycles to obtain both desirable clinical outcome and lower multiple pregnancy rates.     

Comparison between the gonadotropin-releasing hormone antagonist protocol and the gonadotropin-releasing hormone agonist long protocol for controlled ovarian hyperstimulation in the first in vitro fertilization–embryo transfer cycle in an unspecified population of infertile couples

Purpose  

We aimed to compare the efficacy of a gonadotropin-releasing hormone (GnRH) antagonist protocol and a GnRH agonist long protocol used in the first in vitro fertilization–embryo transfer (IVF–ET) cycle in an unspecified population of infertile couples.     

Is there a critical LH level for hCG trigger after the detection of LH surge in modified natural frozen-thawed single blastocyst transfer cycles?

PurposeThere is no consensus yet in the literature on an optimal luteinizing hormone (LH) level for human chorionic gonadotrophin (hCG) trigger timing in patients undergoing frozen-thawed embryo transfer (FET) with modified natural cycles (mNC). The objective of our study was to compare the clinical results of hCG trigger at different LH levels in mNC-FET cases.MethodsThis retrospective study was conducted in Istanbul Memorial Hospital ART and Genetics Center. A total of 1076 cases with 1163 mNC-FET cycles were evaluated. LH levels between the start of LH rise (15 IU/L) and LH peak level (> 40 IU/L) were evaluated. Cycles were analyzed in four groups: group A (n = 287) LH level on the day prior to the day of hCG; groups B, C and D, LH levels on the day of hCG: group B (n = 245) LH 15–24.9; group C (n = 253), LH 25–39.9; group D (n = 383) LH ≥ 40. Cycle outcomes in the four groups were compared.ResultsSubgroup analyses of mNC-FET groups showed that implantation, clinical and ongoing pregnancy rates, and pregnancy losses were not significantly different in patients with different LH levels on the day of hCG trigger.ConclusionOur study suggests that hCG can be administered at any time between the start of LH rise (≥ 15 IU/L) and LH peak level (≥ 40 IU/L) without a detrimental effect on clinical outcome.     

Does 45,X/46,XX mosaicism with 6–28% of aneuploidy affect the outcomes of IVF or ICSI?

Objective

Several studies have shown an increased frequency of chromosomal aberrations in female partners of couples examined prior to intracytoplasmic sperm injection (ICSI). A retrospective cohort study was performed to determine whether 45,X/46,XX mosaicism affects the outcomes of in vitro fertilization (IVF) or ICSI.

Study design

Forty-six women with a 45,X/46,XX karyotype with 6–28% of aneuploidy were compared with 59 control women (46,XX), matched for age, from the female population who underwent IVF or ICSI between 1 January 1996 and 31 December 2006 at the Reproductive Medicine Unit at Brest University Hospital. The outcomes of 254 treatment cycles were compared according to patient karyotype.

Results

No difference was found in the number of retrieved oocytes (8.9 ± 5.5 vs 8.5 ± 4.7; p = 0.56) or the number of mature oocytes (7.4 ± 4.7 vs 6.9 ± 4.2; p = 0.49) between the 45,X/46,XX group and the 46,XX group, respectively. Fertilization rates did not differ between the groups for either IVF or ICSI. In addition, no difference was found in the pregnancy rate by cycle (17.4% vs 18.7%, respectively; p = 0.87). The percentage of first-trimester miscarriages was similar in both groups (13.6% vs 12.5%, respectively; p = 0.51).

Conclusion

45,X/46,XX mosaicism with 6–28% of aneuploidy has no adverse effect on the outcomes of IVF or ICSI among women referred to assisted reproductive technologies.     

Does the type of GnRH analogue used,affect live birth rates in women with endometriosis undergoing IVF/ICSI treatment,according to the rAFS stage?

Since the introduction of gonadotropin-releasing hormone (GnRH) antagonists, an extensive amount of literature investigating the role of the downregulation protocols on pregnancy outcomes has been published. However, these studies were mainly performed in the general infertile population where patients with endometriosis were often excluded or underrepresented. This study is a large retrospective cohort study including 386 endometriosis patients undergoing IVF/ICSI, who had been previously classified according to the rAFS system. Patients were stimulated either a long GnRH agonist or GnRH antagonist protocol. Depending on endometriosis stage, patients were divided into two groups: endometriosis stage I–II and endometriosis stage III–IV. Each group was subdivided, based on the type GnRH analog used. When comparing the GnRH agonist and antagonist groups, patients with endometriosis stage I–II, had a tendency toward higher β-hCG positive, clinical pregnancy, and live birth rates (42.8% vs. 26.7%; p?=?.07) in favor of GnRH agonist use. In endometriosis stage III–IV, no differences were observed between agonist and antagonist cycle in any of the pregnancy outcomes. Multivariate regression analysis did not reveal any significant predictor of live birth after adjusting for relevant confounders. Based on our findings, the chance to have a liveborn in endometriosis population seems not to be affected by the type of GnRH analog used, at least in advanced stages. Findings from stage I–II endometriosis cases merit consideration and further evaluation in a larger sample size is warranted.     

Endometrioma undergoing laparoscopic ovarian cystectomy: its influence on the outcome of in vitro fertilization and embryo transfer (IVF–ET)

PURPOSE: To evaluate the effect of laparoscopic ovarian cystectomy for endometrioma on the clinical outcome of IVF treatment. METHODS: Patients who received IVF treatment were retrospectively classified into two groups. Group 1 included 95 patients who received IVF due to tubal occlusion. Group 2 included 127 patients who had received laparoscopic ovarian cystectomy for endometrioma(s) followed by IVF treatment. Clinical outcomes of IVF treatment were compared between two groups. RESULTS: More oocytes were harvested per retrieval in Group 1 than Group 2 (p < 0.05). The fertilization rate was higher in Group 1 than Group 2 (p < 0.05). Although the implantation rate was higher in Group 2 (p < 0.05), the clinical pregnancy rate revealed no statistically significant difference between the two groups. CONCLUSIONS: Women who received ovarian cystectomy for endometriomas have fewer oocytes harvested during IVF treatment. However, their chance of pregnancy was comparable to patients with tubal problems who underwent IVF treatment.