Which factors affect the likelihood of miscarriage after single euploid blastocyst transfer?

Research questionWhich parameters affect the likelihood of miscarriage after single euploid frozen–thawed blastocyst transfer (FBT)?DesignIn this retrospective study, clinical and laboratory data from 1051 single euploid FBTs were evaluated. Exclusion criteria were endocrine or systemic pathologies, uterine anomalies or pathologies, unilateral or bilateral hydrosalpinx, karyotypic abnormalities (either maternal or paternal) or thrombophilia. Patients were divided into two groups according to pregnancy outcome: live birth and miscarriage.ResultsBody mass index (BMI) (25.98 ± 0.5 versus 24.36 ± 0.21, P = 0.019), duration of infertility (6.62 ± 0.54 versus 4.92 ± 0.18, P = 0.006) and number of previous miscarriages (1.36 ± 0.13 versus 0.79 ± 0.05, P < 0.001) were significantly higher in the miscarriage group (n = 100) than in the live birth group (n = 589). Although the trophectoderm and inner cell mass (ICM) percentage scores were not statistically different among the miscarriage and live birth groups, the percentage of day-6 biopsied embryos was significantly higher in the miscarriage group. Binary logistic regression analysis revealed that BMI (OR 1.083, 95% CI 1.013 to 1.158, P = 0.02) and number of previous miscarriages (OR 1.279, 95% CI 1.013 to 1.158, P = 0.038) were independent factors for miscarriage. Patients with elevated BMI and a higher number of miscarriages were at increased risk of miscarriage.ConclusionAfter a single euploid FBT, BMI and number of previous miscarriages are predictors of miscarriage. Lifestyle interventions before FBT may decrease miscarriage rates.     

Does increasing estrogen dose during frozen embryo transfer affect pregnancy rate?

Journal of Assisted Reproduction and Genetics - To assess the effect of increasing estrogen doses during hormone therapy frozen embryo transfer (HT-FET) cycles on endometrial thickness and success...     

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.     

Do day-3 embryo grade predict day-5 blastocyst transfer outcomes in patients with good prognosis?

The main aim was to investigate whether or not day-3 embryo grade could predict day-5 blastocyst transfer outcomes in patients with good prognosis. This study included 233 elective single blastocyst transfers (eSBT) by D5 selection with conventional morphology (CM) and 121 elective single blastocyst transfers (eSBT) by D5 selection with time-lapse monitoring system (TL) from October 2016 to October 2017. All the patients were submitted to controlled ovarian stimulation (COS) with long-term protocol and transferred for the first time. The main outcome measures were clinical pregnancy rates (CPR) and ongoing pregnancy (OPR). Our results suggested that CPR (58.04 versus 57.89 versus 55.56%; p?=?.957) and OPR (66.07 versus 65.79 versus 64.44%; p?=?.981) were comparable among day 3 grades I, grades II, and grades III groups. We also observed that the TL group showed a slightly better CPR and OPR than CM group (p?>?.05). Our findings suggested that good or poor embryos at day-3 were not predictive of the outcomes of good-quality blastocysts in a good-prognosis population. It needed to be emphasized that time-lapse monitoring might be useful for elective single blastocyst transfer.     

HCG administration after endogenous LH rise negatively influences pregnancy rate in modified natural cycle for frozen–thawed euploid blastocyst transfer: a pilot study

Purpose

The aim of the present study was to evaluate whether in a modified natural cycle (modified-NC) for a frozen-thawed single euploid blastocyst transfer, a critical LH value, above which human chorionic gonadotropin (hCG) administration should be avoided, may be defined.

Methods

One hundred and sixty-seven patients underwent modified natural cycle in order to transfer a single frozen-thawed euploid blastocyst. All embryos were obtained by intracytoplasmic sperm injection and were biopsied at the blastocyst stage and analyzed by means of array comparative genomic hybridization (aCGH). Ovulation was induced using 10.000 IU hCG when the mean follicle diameter was at least of 17 mm, independently from LH values. The primary end points were the hCG-positive test and clinical pregnancy. The interim analysis showed that LH value ≥?13 mIU/ml on the day of hCG injection may negatively influence the clinical results, suggesting that in this condition, it should be advisable waiting for spontaneous ovulation.

Results

Among patients who received hCG for ovulation induction, the hCG-positive test and clinical pregnancy rates in modified-NC were significantly lower in cycles with LH?≥?13 mIU/ml in respect to those with LH?<?13 mIU/ml (45.4 vs 73.3 and 36.4 vs 65.9%, in LH?≥?13 and LH?<?13 groups, respectively). In patients with LH value ≥?13 mIU/ml, hCG administration led to significantly lower rates of hCG-positive test (45.4 vs 74.5% in hCG administration and spontaneous ovulation groups, respectively) and clinical pregnancy (36.4 vs 64.7% in hCG administration and spontaneous ovulation groups, respectively). The baseline patient characteristics were comparable in all groups.

Conclusions

The findings of this study highlight that LH elevation ≥?13 mIU/ml prior to hCG administration may negatively affect clinical pregnancy rates in modified-NC for single euploid blastocyst transfer. The LH determination should be routinely performed during follicular monitoring. In the presence of LH level ≥?13 mIU/ml, hCG administration should be avoided, and the embryo transfer should be planned only after spontaneous follicular rupture.

     

Does the timing of mock embryo transfer affect in vitro fertilization implantation and pregnancy rates?

The timing of a mock embryo transfer does not affect in vitro fertilization implantation or pregnancy rates. Performing a mock embryo transfer at the time of oocyte retrieval, 3 to 5 days before embryo transfer, does not have a deleterious effect on the endometrium.     

Does single embryo transfer improve the obstetric and neonatal outcome of singleton pregnancy?

Singleton pregnancies following in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are associated with increased risks of abnormal placentation, pre-eclampsia and preterm birth. These risks might partly be a consequence of the number of transferred embryos. In this commentary we summarize the results of three observational studies and one randomized study with 1052 pregnancies following single embryo transfer (SET). An increased age- and parity-adjusted risk of gestational hypertension and placenta previa in the SET pregnancies as compared to the spontaneously conceiving controls was reported in one of the studies. Preterm births occurred in 6-12% of SET pregnancies and 4-6% of the newborns were of low birth weight (LBW). The frequency of preterm birth and LBW after SET were considered either lower than or similar to those after double embryo transfer (DET) but higher than after spontaneous conception. Comparison of SET and DET pregnancies thus shows heterogeneous results. Still, it seems that not even a transfer of one good-quality embryo at a time diminishes all the previously identified increased risks of certain obstetric complications and preterm births in singleton pregnancies following IVF or ICSI.     

Luteal estrogen supplementation in stimulated cycles may improve the pregnancy rate in patients undergoing in vitro fertilization/intracytoplasmic sperm injection–embryo transfer

Objective. To evaluate the effect of estradiol addition to progesterone supplementation during the luteal phase on pregnancy and implantation rates in patients undergoing in vitro fertilization/intracytoplasmic sperm injection–embryo transfer (IVF/ICSI-ET) cycles.

Methods. In this prospective, randomized study, carried out in an IVF unit of a university hospital, we studied patients who were undergoing IVF/ICSI with controlled ovarian hyperstimulation using a gonadotropin-releasing hormone agonist/human recombinant gonadotropin long protocol. The main outcome measures were the pregnancy and implantation rates measured in the two groups.

Results. Our results suggest higher pregnancy and implantation rates in IVF/ICSI-ET cycles that were supplemented with estradiol in the luteal phase.

Conclusions. Estradiol supplementation during the luteal phase in women undergoing IVF/ICSI-ET has a beneficial effect on the outcome without (at least, as seems from this study) having any adverse effects.     

Does salpingectomy affect the ipsilateral ovarian response to gonadotropin during in vitro fertilization–embryo transfer cycles?

In a study on the influence of salpingectomy on the same patient ipsilateral ovarian response, 15 patients who were admitted to our department with the diagnosis of uni- or bilateral hydrosalpinges and who were successfully treated by laparoscopic salpingectomy were evaluated. The observed significant decrease in the ipsilateral ovarian response after salgingectomy, as reflected by the quantity of developing follicles during controlled ovarian hyperstimulation for IVF, should be presented to patients during the decision-making process, before offering salpingectomy for the treatment of hydrosalpinx.     

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.     

PCOS patients; how the endometrium can be ready for frozen embryo transfer? A retrospective study

Study objective

Frozen-thawed embryo transfer (FET) avoids the nightmare of developing ovarian hyperstimulation syndrome in PCOS patients during IVF. Ideal protocols of Endometrium preparation in PCOS patients are lacking and need further declaration.

Vaginal progesterone supplementation has no effect on ongoing pregnancy rate in hCG-induced natural frozen–thawed embryo transfer cycles

Objective

The purpose of this study is to assess the effect of luteal phase supplementation (LPS) on pregnancy rates in human chorionic gonadotropin (hCG)-induced natural frozen–thawed (FET) cycles.

Study design

All performed hCG-induced natural FET cycles from January 2006 until August 2007 were retrospectively identified. The study group consisted of 452 cycles: 243 supplemented with progesterone administration (600 mg natural micronized progesterone in three separate doses) and 209 without progesterone. Analysis was limited to cycles where embryos were cryopreserved on day 3. Final oocyte maturation was achieved by hCG when endometrial thickness of ≥7 mm and a follicle of 17 mm were present on ultrasound.

Results

No statistically significant differences were observed in ongoing pregnancy rate between the two groups (22% versus 21%, p = 0.8; difference +1%; 95% confidence interval (CI): −6.5 to +8.7). The non-significant effect of the presence or not of luteal support on pregnancy rate was confirmed by logistic regression (odds ratio (OR): 0.9, 95% CI: 0.54–1.47, P = 0.64). A previous pregnancy following fresh embryo transfer (OR: 6.04, 95% CI: 3.63–10.02, P = 0.001) and increased endometrial thickness (OR: 1.25, 95% CI: 1.11–1.41, P = 0.001) significantly affected the achievement of ongoing pregnancy, whereas the association between embryo score and achievement of pregnancy was marginally significant (OR:0.28, 95% CI: 0.08–0.97, P = 0.05).

Conclusion

There is no convincing evidence to support the use of LPS in hCG-induced natural FET cycles, since there is no luteal phase defect. Further prospective randomized studies are necessary to confirm these findings.     

Comprehensive genetic assessment of the human embryo: can empiric application of microarray comparative genomic hybridization reduce multiple gestation rate by single fresh blastocyst transfer?

Purpose

The unacceptable multiple gestation rate currently associated with in vitro fertilization (IVF) would be substantially alleviated if the routine practice of transferring more than one embryo were reconsidered. While transferring a single embryo is an effective method to reduce the clinical problem of multiple gestation, rigid adherence to this approach has been criticized for negatively impacting clinical pregnancy success in IVF. In general, single embryo transfer is viewed cautiously by IVF patients although greater acceptance would result from a more effective embryo selection method.

Methods

Selection of one embryo for fresh transfer on the basis of chromosomal normalcy should achieve the dual objective of maintaining satisfactory clinical pregnancy rates and minimizing the multiple gestation problem, because embryo aneuploidy is a major contributing factor in implantation failure and miscarriage in IVF. The initial techniques for preimplantation genetic screening unfortunately lacked sufficient sensitivity and did not yield the expected results in IVF. However, newer molecular genetic methods could be incorporated with standard IVF to bring the goal of single embryo transfer within reach.

Results

Aiming to make multiple embryo transfers obsolete and unnecessary, and recognizing that array comparative genomic hybridization (aCGH) will typically require an additional 12?h of laboratory time to complete, we propose adopting aCGH for mainstream use in clinical IVF practice.

Conclusion

As aCGH technology continues to develop and becomes increasingly available at lower cost, it may soon be considered unusual for IVF laboratories to select a single embryo for fresh transfer without regard to its chromosomal competency. In this report, we provide a rationale supporting aCGH as the preferred methodology to provide a comprehensive genetic assessment of the single embryo before fresh transfer in IVF. The logistics and cost of integrating aCGH with IVF to enable fresh embryo transfer are also discussed.