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1.
Fertil Steril ; 122(1): 106-113, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38342371

ABSTRACT

OBJECTIVE: To evaluate whether laser-mediated assisted hatching (AH) performed on vitrified/warmed blastocysts before embryo transfer can improve live birth rate. DESIGN: The "pArtiaL zonA pelluciDa removal by assisteD hatchINg of blastocysts (ALADDIN)" is a 2-center comparative study with a parallel randomized controlled design. SETTING: University hospital. PATIENTS: Participants were recruited between September 2018 and November 2021. They were aged 18-39 years, underwent nondonor in vitro fertilization cycles, and were scheduled for elective single embryo transfer with vitrified/warmed blastocysts. Those with uterine abnormalities, body mass index of >35 kg/m2, severe male factor infertility, or performing preimplantation genetic testing were excluded. INTERVENTION: Assisted hatching was performed using a 1,480 nm diode laser, removing approximately one-third of the zona pellucida with continuous 0.2 ms pulses applied from the 1-5 o'clock positions. MAIN OUTCOME MEASURES: The primary outcome was the live birth rate. Secondary end points included clinical pregnancy, miscarriage, multiple pregnancies, preterm births, obstetric and neonatal complications, and congenital anomalies. RESULTS: Overall, 698 participants met the inclusion criteria and were randomized: 352 patients were assigned to the AH arm and 346 to the control arm. Of the participants, 105 (29.8%) and 101 (29.2%), respectively, achieved a live birth after treatment. The relative risk of live birth in patients with vitrified/warmed blastocysts treated with AH was 1.02 (95% confidence interval, 0.86-1.19). Exploratory subgroup analyses for women's age, recruiting centers, indications for in vitro fertilization, method of insemination, blastocyst quality, and days of blastocyst development failed to highlight any clinical situation that could benefit from AH in thawed blastocysts. CONCLUSION: In patients undergoing frozen embryo transfer with vitrified/warmed blastocysts, laser AH does not improve the live birth rate. Further studies are required to rule out milder but potentially interesting benefits in specific subgroups of patients. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03623659.


Subject(s)
Blastocyst , Live Birth , Pregnancy Rate , Vitrification , Humans , Female , Adult , Pregnancy , Cryopreservation/methods , Zona Pellucida , Young Adult , Fertilization in Vitro/methods , Infertility/therapy , Infertility/physiopathology , Infertility/diagnosis , Adolescent , Embryo Transfer/methods , Embryo Transfer/adverse effects , Treatment Outcome , Embryo Culture Techniques , Single Embryo Transfer/methods , Single Embryo Transfer/adverse effects , Lasers , Male
2.
Reprod Biol Endocrinol ; 22(1): 26, 2024 Feb 21.
Article in English | MEDLINE | ID: mdl-38383391

ABSTRACT

BACKGROUND: To evaluate the impact of embryo quality and quantity, specifically a poor quality embryo (PQE) in combination with a good quality embryo (GQE), by double embryo transfer (DET) on the live birth rate (LBR) and neonatal outcomes in patients undergoing frozen-thawed embryo transfer (FET) cycles. METHODS: A study on a cohort of women who underwent a total of 1462 frozen-thawed cleavage or blastocyst embryo transfer cycles with autologous oocytes was conducted between January 2018 and December 2021. To compare the outcomes between single embryo transfer (SET) with a GQE and DET with a GQE and a PQE, propensity score matching (PSM) was applied to control for potential confounders, and a generalized estimating equation (GEE) model was used to determine the association between the effect of an additional PQE and the outcomes. Subgroup analysis was also performed for patients stratified by female age. RESULTS: After PS matching, DET-GQE + PQE did not significantly alter the LBR (adjusted odds ratio [OR] 1.421, 95% CI 0.907-2.228) compared with SET-GQE in cleavage-stage embryo transfer but did increase the multiple birth rate (MBR, [OR] 3.917, 95% CI 1.189-12.911). However, in patients who underwent blastocyst-stage embryo transfer, adding a second PQE increased the live birth rate by 7.8% ([OR] 1.477, 95% CI 1.046-2.086) and the multiple birth rate by 19.6% ([OR] 28.355, 95% CI 3.926-204.790), and resulted in adverse neonatal outcomes. For patients who underwent cleavage-stage embryo transfer, transferring a PQE with a GQE led to a significant increase in the MBR ([OR] 4.724, 95% CI 1.121-19.913) in women under 35 years old but not in the LBR ([OR] 1.227, 95% CI 0.719-2.092). The increases in LBR and MBR for DET-GQE + PQE compared with SET-GQE in women older than 35 years were nonsignificant toward. For patients who underwent blastocyst-stage embryo transfer, DET-GQE + PQE had a greater LBR ([OR] 1.803, 95% CI 1.165-2.789), MBR ([OR] 24.185, 95% CI 3.285-178.062) and preterm birth rate (PBR, [OR] 4.092, 95% CI 1.153-14.518) than did SET-GQE in women under 35 years old, while no significant impact on the LBR ([OR] 1.053, 95% CI 0.589-1.884) or MBR (0% vs. 8.3%) was observed in women older than 35 years. CONCLUSIONS: The addition of a PQE has no significant benefit on the LBR but significantly increases the MBR in patients who underwent frozen-thawed cleavage-stage embryo transfer. However, for patients who underwent blastocyst-stage embryo transfer, DET-GQE + PQE resulted in an increase in both the LBR and MBR, which may lead to adverse neonatal outcomes. Thus, the benefits and risks of double blastocyst-stage embryo transfer should be balanced. In patients younger than 35 years, SET-GQE achieved satisfactory LBR either in cleavage-stage embryo transfer or blastocyst-stage embryo transfer, while DET-GQE + PQE resulted in a dramatically increased MBR. Considering the low LBR in women older than 35 years who underwent single cleavage-stage embryo transfer, selective single blastocyst-stage embryo transfer appears to be a more promising approach for reducing the risk of multiple live births and adverse neonatal outcomes.


Subject(s)
Fertilization in Vitro , Premature Birth , Pregnancy , Female , Humans , Infant, Newborn , Adult , Fertilization in Vitro/methods , Premature Birth/etiology , Embryo Transfer/methods , Pregnancy, Multiple , Single Embryo Transfer/adverse effects , Live Birth , Pregnancy Rate , Retrospective Studies
4.
J Assist Reprod Genet ; 39(7): 1603-1610, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35551564

ABSTRACT

PURPOSE: To study the associations between fetal fraction at the first trimester and subsequent adverse pregnancy outcomes (APOs) in IVF singleton pregnancies with single embryo transfer from frozen cycles. METHODS: This is a single-center retrospective cohort study on IVF singleton pregnancies with single embryo transfer from frozen cycles. A total of 8457 women were collected between March 2015 and September 2018 from the Center for Reproductive Medicine, Shandong University, China. Participants underwent cell-free DNA (cfDNA) sequencing at 11-13 weeks' gestation. Multivariable logistic regressions were performed with the risk of APOs based on various predictor variables. RESULTS: A total of 8457 women were included in the analysis of which 1563 (18.48%) women developed one or more APOs. The hypertensive disorders of pregnancy (HDP) (N = 515), gestational diabetes mellitus (GDM) (N = 684), preterm birth (PTB) (N = 567), and low birth weight (LBW) (N = 306) groups had lower fetal fraction compared with the no pregnancy complication (NPC) group (all p values < 0.05). Based on the multivariable logistic regression results, the optimal cutoff values of fetal fraction were 9.30%, 12.54%, 9.10%, 12.65%, and 13.83% for at least one APO, HDP, GDM, PTB, and LBW, respectively. After adjustment for potential maternal confounders, women in the low fetal fraction (LFF) group had a higher risk for the APOs compared with high fetal fraction (HFF) group. CONCLUSIONS: The fetal fraction in HDP, GDM, PTB, and LBW groups were lower than NPC group in IVF singleton pregnancies with single embryo transfer from frozen cycles in China.


Subject(s)
Pregnancy Outcome , Premature Birth , Female , Fertilization in Vitro/adverse effects , Humans , Infant, Newborn , Male , Pregnancy , Pregnancy Trimester, First , Premature Birth/etiology , Retrospective Studies , Single Embryo Transfer/adverse effects
5.
Reprod Biol Endocrinol ; 20(1): 20, 2022 Jan 27.
Article in English | MEDLINE | ID: mdl-35086551

ABSTRACT

BACKGROUND: Evidence referring to the trade-offs between the benefits and risks of single embryo transfer (SET) versus double embryo transfer (DET) following assisted reproduction technology are insufficient, especially for those women with a defined embryo quality or advanced age. METHODS: A systematic review and meta-analysis was conducted according to PRISMA guidelines. PubMed, EMBASE, Cochrane Library and ClinicalTrials.gov were searched based on established search strategy from inception through February 2021. Pre-specified primary outcomes were live birth rate (LBR) and multiple pregnancy rate (MPR). Odds ratio (OR) with 95% confidence interval (CI) were pooled by a random-effects model using R version 4.1.0. RESULTS: Eighty-five studies (14 randomized controlled trials and 71 observational studies) were eligible. Compared with DET, SET decreased the probability of a live birth (OR = 0.78, 95% CI: 0.71-0.85, P < 0.001, n = 62), and lowered the rate of multiple pregnancy (0.05, 0.04-0.06, P < 0.001, n = 45). In the sub-analyses of age stratification, both the differences of LBR (0.87, 0.54-1.40, P = 0.565, n = 4) and MPR (0.34, 0.06-2.03, P = 0.236, n = 3) between SET and DET groups became insignificant in patients aged ≥40 years. No significant difference in LBR for single GQE versus two embryos of mixed quality [GQE + PQE (non-good quality embryo)] (0.99, 0.77-1.27, P = 0.915, n = 8), nor any difference of MPR in single PQE versus two PQEs (0.23, 0.04-1.49, P = 0.123, n = 6). Moreover, women who conceived through SET were associated with lower risks of poor outcomes, including cesarean section (0.64, 0.43-0.94), antepartum haemorrhage (0.35, 0.15-0.82), preterm birth (0.25, 0.21-0.30), low birth weight (0.20, 0.16-0.25), Apgar1 < 7 rate (0.12, 0.02-0.93) or neonatal intensive care unit admission (0.30, 0.14-0.66) than those following DET. CONCLUSIONS: In women aged < 40 years or if any GQE is available, SET should be incorporated into clinical practice. While in the absence of GQEs, DET may be preferable. However, for elderly women aged ≥40 years, current evidence is not enough to recommend an appropriate number of embryo transfer. The findings need to be further confirmed.


Subject(s)
Embryo Transfer/adverse effects , Embryo Transfer/methods , Female , Humans , Infant, Newborn , Male , Pregnancy , Pregnancy Outcome/epidemiology , Pregnancy, Twin/physiology , Pregnancy, Twin/statistics & numerical data , Risk Assessment , Single Embryo Transfer/adverse effects , Single Embryo Transfer/methods , Single Embryo Transfer/statistics & numerical data , Twins
6.
Fertil Steril ; 117(2): 339-348, 2022 02.
Article in English | MEDLINE | ID: mdl-34802685

ABSTRACT

OBJECTIVE: To examine the differences in live birth rates (LBRs), with single embryo transfer (SET), using oocytes from program generated egg donors vs. commercial egg bank donors and other factors affecting LBRs using donor oocytes. DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENT(S): A total of 40,485 in vitro fertilization cycles using donor oocytes reported to the Society for Assisted Reproductive Technology registry in 2016-2018. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Live birth rate and cumulative LBR for SET using donor oocytes. RESULT(S): Multivariate results from the first SET from 19,128 cycles, including 15,429 from program generated egg donors and 3,699 from commercial egg banks, showed, when controlling for all other variables, the following: the LBR in the first SET cycle using commercial egg banks was 53.3% compared with 55.4% using program recruited egg donors (odds ratio [OR], 0.92); a reduction in the LBR with increasing recipient age, ages 40-44 years (OR, 0.80), 45-49 years (OR, 0.77), and >49 years (OR, 0.65); a steady decline in the LBR with increases in recipient body mass index above normal; and a steady increase in the LBR in association with >16 oocytes retrieved. Double embryo transfer increased the LBR (SET, 52%, vs. double embryo transfer, 58%) but also significantly increased the multiple pregnancy LBR, with 43% twins and 0.9% triplets. Blastocyst transfer had a higher LBR than cleavage stage embryos (52.5% vs. 39.5%). Intracytoplasmic sperm injection vs. conventional insemination when using fresh oocytes from program donors had similar LBRs. CONCLUSION(S): When performing in vitro fertilization using donor oocytes with SET, the LBR is affected by oocyte source, recipient age, recipient body mass index, stage of embryo at transfer, and number of oocytes retrieved.


Subject(s)
Biological Specimen Banks , Fertilization in Vitro , Infertility/therapy , Oocyte Donation , Single Embryo Transfer , Adult , Body Mass Index , Cryopreservation , Female , Fertility , Fertilization in Vitro/adverse effects , Humans , Infertility/diagnosis , Infertility/physiopathology , Live Birth , Male , Maternal Age , Middle Aged , Oocyte Donation/adverse effects , Oocyte Retrieval , Pregnancy , Registries , Retrospective Studies , Risk Assessment , Risk Factors , Single Embryo Transfer/adverse effects , Societies, Medical , Treatment Outcome
7.
Fertil Steril ; 116(4): 1172-1180, 2021 10.
Article in English | MEDLINE | ID: mdl-34246469

ABSTRACT

OBJECTIVE: To analyze the performance of an annotation-free embryo scoring system on the basis of deep learning for pregnancy prediction after single vitrified blastocyst transfer (SVBT) compared with the performance of other blastocyst grading systems dependent on annotation or morphology scores. DESIGN: A single-center large cohort retrospective study from an independent validation test. SETTING: Infertility clinic. PATIENT(S): Patients who underwent SVBT cycles (3,018 cycles, mean ± SD patient age 39.3 ± 4.0 years). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The pregnancy prediction performances of each embryo scoring model were compared using the area under curve (AUC) for predicting the fetal heartbeat status for each maternal age group. RESULT(S): The AUCs of the <35 years age group (n = 389) for pregnancy prediction were 0.72 for iDAScore, 0.66 for KIDScore, and 0.64 for the Gardner criteria. The AUC of iDAScore was significantly greater than those of the other two models. For the 35-37 years age group (n = 514), the AUCs were 0.68, 0.68, and 0.65 for iDAScore, KIDScore, and the Gardner criteria, respectively, and were not significantly different. The AUCs of the 38-40 years age group (n = 796) were 0.67 for iDAScore, 0.65 for KIDScore, and 0.64 for the Gardner criteria, and there were no significant differences. The AUCs of the 41-42 years age group (n = 636) were 0.66, 0.66, and 0.63 for iDAScore, KIDScore, and the Gardner criteria, respectively, and there were no significant differences among the pregnancy prediction models. For the >42 years age group (n = 389), the AUCs were 0.76 for iDAScore, 0.75 for KIDScore, and 0.75 for the Gardner criteria, and there were no significant differences. Thus, iDAScore AUC was either the highest or equal to the highest AUC for all age groups, although a significant difference was observed only in the youngest age group. CONCLUSION(S): Our results showed that objective embryo assessment by a completely automatic and annotation-free model, iDAScore, performed as well as or even better than more traditional embryo assessment or annotation-dependent ranking tools. iDAScore could be an optimal pregnancy prediction model after SVBT, especially in young patients.


Subject(s)
Blastocyst/pathology , Cryopreservation , Deep Learning , Fertilization in Vitro , Heart Rate, Fetal , Image Interpretation, Computer-Assisted , Infertility/therapy , Single Embryo Transfer , Time-Lapse Imaging , Adult , Embryo Culture Techniques , Embryo Implantation , Female , Fertilization in Vitro/adverse effects , Humans , Infertility/diagnosis , Infertility/physiopathology , Maternal Age , Middle Aged , Predictive Value of Tests , Pregnancy , Pregnancy Rate , Retrospective Studies , Single Embryo Transfer/adverse effects , Treatment Outcome , Vitrification
8.
Fertil Steril ; 116(3): 784-792, 2021 09.
Article in English | MEDLINE | ID: mdl-34023069

ABSTRACT

OBJECTIVE: To identify the risk of stillbirth from in vitro types of assisted reproductive technologies compared with spontaneous conception (SC), limited to singleton births. DESIGN: Systematic literature search and search chaining on online databases: PubMed, Embase, and Scopus. SETTING: Not applicable. PATIENT(S): Singleton pregnancies from in vitro fertilization (IVF) or fertilization by IVF and intracytoplasmic sperm injection (IVF-ICSI). INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Adjusted odds ratio for stillbirth or prevalence of stillbirth in case-control groups of IVF/IVF-ICSI singletons and SCs, respectively, in matched studies. RESULT(S): A total of 19 studies were included, and study quality was mixed. Ten studies qualified for inclusion to the meta-analysis, which revealed a significantly increased risk of stillbirth in IVF/IVF-ICSI compared with that in SC (odds ratio [95% confidence interval]: 1.82 [1.37-2.42]), and there was no evidence of publication bias. CONCLUSION(S): In vitro fertilization and IVF-ICSI treatment increases the risk of stillbirth compared with natural conception. CLINICAL TRIAL REGISTRATION NUMBER: PROSPERO 216768.


Subject(s)
Fertilization in Vitro/adverse effects , Infertility/therapy , Single Embryo Transfer/adverse effects , Stillbirth/epidemiology , Female , Humans , Infertility/diagnosis , Infertility/physiopathology , Male , Pregnancy , Prevalence , Risk Assessment , Risk Factors , Sperm Injections, Intracytoplasmic/adverse effects , Treatment Outcome
9.
Fertil Steril ; 115(6): 1471-1477, 2021 06.
Article in English | MEDLINE | ID: mdl-33691932

ABSTRACT

OBJECTIVE: To compare gestational age, birth weight (BW), and live birth rates in gestational carriers (GC) after the transfer of 1 or 2 frozen embryo(s) with or without preimplantation genetic testing for aneuploidy (PGT-A), with the understanding that several social and economic factors may motivate intended parents to request the transfer of 2 embryos and/or PGT-A when using a GC. DESIGN: Retrospective cohort study SETTING: An assisted reproductive technology practice. PATIENT(S): All frozen blastocyst transfers with GCs from 2009-2018. INTERVENTION(S): One or 2 embryo frozen embryo transfers with and without PGT-A. MAIN OUTCOME MEASURE(S): Live birth, preterm birth, and low BW. RESULTS: A total of 583 frozen embryo transfer cycles with vitrified high-grade blastocysts (grade BB or higher) to GCs were analyzed. Although the live birth rate was significantly greater in frozen embryo transfers with 2 embryos, after single embryo transfer (SET), the mean gestational age and BW of live births were statistically significantly greater than those of double embryo transfer (DET). The rate of multiple births was 1.9% for SET compared to 20.0% for DET per transfer. Only 3.8% of live births from SET experienced low BW and 0.6% had very low or extremely low BW. By comparison, 12.5% of DET live births were low BW and 5% were very low BW. After SET, 13.4% of live births were preterm, compared with 40% in DET. The analysis also included a total of 194 transfers with PGT-A compared to 389 cycles without. Overall, live births per transfer were not significantly different between these latter 2 subgroups. CONCLUSION: Frozen embryo transfer cycles in GCs with DET were associated with more preterm births and lower birth weights compared with those of SET. Intended parents and GCs should be counseled that DET is associated with greater risks of adverse pregnancy and perinatal outcomes, which mitigates higher live birth rates. The use of PGT-A did not appear to improve the live birth rate.


Subject(s)
Blastocyst/pathology , Cryopreservation , Fertilization in Vitro , Preimplantation Diagnosis , Single Embryo Transfer , Surrogate Mothers , Birth Weight , Embryo Implantation , Female , Fertilization in Vitro/adverse effects , Gestational Age , Humans , Infant, Low Birth Weight , Infant, Newborn , Live Birth , Pregnancy , Pregnancy Rate , Preimplantation Diagnosis/adverse effects , Premature Birth/etiology , Retrospective Studies , Risk Factors , Single Embryo Transfer/adverse effects , Treatment Outcome
10.
Fertil Steril ; 115(6): 1487-1494, 2021 06.
Article in English | MEDLINE | ID: mdl-33487443

ABSTRACT

OBJECTIVE: To investigate the association of endometrium preparation with perinatal outcomes. DESIGN: Retrospective cohort study. SETTING: University-affiliated fertility center. PATIENT(S): Twenty-one thousand six hundred and forty-eight women who underwent frozen single-blastocyst transfer from January 2013 to March 2019. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Cesarean delivery, preterm delivery (PTD), vaginal PTD, very preterm delivery (VPTD), postterm delivery, low birth weight (LBW), macrosomia, small for gestational age (SGA), large for gestational age (LGA), hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), premature rupture of membrane (PROM), placenta previa, and congenital abnormality. RESULT(S): Compared with natural cycles, hormone replacement cycles were associated with an increased risk of PTD, VPTD, cesarean delivery, macrosomia, PROM, and HDP. There was a trend toward an increased risk of vaginal PTD and LGA in hormone replacement cycles. Stimulated cycles were associated with an increased risk of postterm delivery and GDM. There was no statistically significant difference in the rate of SGA, placenta previa, or congenital abnormality among the three endometrium preparation methods. CONCLUSION(S): Hormone replacement cycles are associated with an increased risk of PTD, VPTD, cesarean delivery, LBW, macrosomia, PROM, and HDP. Stimulated cycles are associated with an increased risk of postterm delivery and GDM.


Subject(s)
Blastocyst , Cryopreservation , Endometrium/drug effects , Fertility Agents, Female/therapeutic use , Infertility/therapy , Single Embryo Transfer , Adult , Cesarean Section , Embryo Implantation/drug effects , Endometrium/physiopathology , Female , Fertility/drug effects , Fertility Agents, Female/adverse effects , Fertilization in Vitro , Humans , Infertility/diagnosis , Infertility/physiopathology , Live Birth , Pregnancy , Pregnancy Complications/etiology , Pregnancy Rate , Retrospective Studies , Single Embryo Transfer/adverse effects , Treatment Outcome
12.
Fertil Steril ; 114(6): 1198-1206, 2020 12.
Article in English | MEDLINE | ID: mdl-33081977

ABSTRACT

OBJECTIVE: To evaluate the risk of ectopic pregnancies (EPs) for fresh cycles according to different ovarian stimulation protocols. DESIGN: Registry-based retrospective cohort study. SETTING: Not applicable. PATIENT(S): A total of 68,851 clinical pregnancies after fresh single embryo transfer between 2007 and 2015. INTERVENTION (S): None MAIN OUTCOME MEASURE(S): Ectopic pregnancies. Odds ratios and 95% confidence intervals for EPs were calculated by using generalized estimating equations adjusted for potential maternal and treatment characteristics. RESULT(S): Among 68,851 clinical pregnancies, 1,049 (1.46%) cases of EP were reported. Compared with natural cycles, all ovarian stimulation protocols were associated with a significantly increased risk of EP. Ovarian stimulation with clomiphene (CC) demonstrated the highest odds ratios for EPs. Significant associations between ovarian stimulation protocols and EP compared with natural cycles were prominent when the number of retrieved oocytes was low (1-3) to moderate (4-7), but there were no significant associations when the number of retrieved oocytes was high (≥8). CONCLUSION(S): Ovarian stimulation protocols were significantly associated with an increased risk of EP. In particular, ovarian stimulation with CC had the highest risk of EP compared with other stimulation protocols. Further studies are essential to investigate possible confounding factors for different ovarian stimulation protocols, especially CC, and the risk of EP.


Subject(s)
Clomiphene/adverse effects , Fertility Agents, Female/adverse effects , Infertility/therapy , Ovulation Induction/adverse effects , Pregnancy, Ectopic/etiology , Single Embryo Transfer/adverse effects , Adult , Female , Fertility , Fertilization in Vitro , Humans , Infertility/diagnosis , Infertility/physiopathology , Japan , Oocyte Retrieval , Pregnancy , Registries , Retrospective Studies , Risk Assessment , Risk Factors , Treatment Outcome
13.
Fertil Steril ; 114(6): 1232-1241, 2020 12.
Article in English | MEDLINE | ID: mdl-32917380

ABSTRACT

OBJECTIVE: To describe novel embryo features capable of predicting implantation potential as input data for an artificial neural network (ANN) model. DESIGN: Retrospective cohort study. SETTING: University-affiliated private IVF center. PATIENT(S): This study included 637 patients from the oocyte donation program who underwent single-blastocyst transfer during two consecutive years. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The research was divided into two phases. Phase 1 consisted of the description and analysis of the following embryo features in implanted and nonimplanted embryos: distance and speed of pronuclear migration, blastocyst expanded diameter, inner cell mass area, and trophectoderm cell cycle length. Phase 2 consisted of the development of an ANN algorithm for implantation prediction. Results were obtained for four models fed with different input data. The predictive power was measured with the use of the area under the receiver operating characteristic curve (AUC). RESULT(S): Out of the five novel described parameters, blastocyst expanded diameter and trophectoderm cell cycle length had statistically different values in implanted and nonimplanted embryos. After the ANN models were trained and validated using fivefold cross-validation, they were capable of predicting implantation on testing data with AUCs of 0.64 for ANN1 (conventional morphokinetics), 0.73 for ANN2 (novel morphodynamics), 0.77 for ANN3 (conventional morphokinetics + novel morphodynamics), and 0.68 for ANN4 (discriminatory variables from statistical test). CONCLUSION(S): The novel proposed embryo features affect the implantation potential, and their combination with conventional morphokinetic parameters is effective as input data for a predictive model based on artificial intelligence.


Subject(s)
Blastocyst/physiology , Embryo Implantation , Fertilization in Vitro , Image Interpretation, Computer-Assisted , Infertility/therapy , Neural Networks, Computer , Single Embryo Transfer , Time-Lapse Imaging , Female , Fertility , Fertilization in Vitro/adverse effects , Humans , Infertility/diagnosis , Infertility/physiopathology , Oocyte Donation , Predictive Value of Tests , Pregnancy , Pregnancy Rate , Retrospective Studies , Single Embryo Transfer/adverse effects , Time Factors , Treatment Outcome
14.
Fertil Steril ; 114(6): 1207-1215, 2020 12.
Article in English | MEDLINE | ID: mdl-32861442

ABSTRACT

OBJECTIVE: To evaluate the efficacy of two different in vitro fertilization culture media for blastocyst development, pregnancy, and live birth rate. Global (GB) medium (used without refreshment) and G-TL medium (designed specifically for culture in time-lapse incubators) were compared. DESIGN: Prospective randomized study of sibling embryo culture in two culture media. SETTING: In vitro fertilization clinic. PATIENT(S): Women undergoing fresh or frozen cycles using autologous or donor oocytes. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary endpoints were implantation, pregnancy, and live birth rate (LBR) after single blastocyst transfer. Secondary endpoints included embryo morphokinetics, development of good-quality blastocysts, and euploidy rate. RESULT(S): Kinetic data from 10,768 sibling pronucleate embryos cultured in the EmbryoScope were compared. GB embryos initiated compaction earlier and formed morula sooner than their G-TL counterparts. The mean timing for start of blastulation did not differ. The interval between start of blastulation and time of blastocyst formation was observed to be <12 hours for proportionately more GB compared with G-TL-cultured embryos. Despite a higher rate of observed dysmorphisms in GB embryos, the euploidy rate among biopsied blastocysts did not differ between media. A total of 820 single-embryo transfer cycles were performed. Implantation rates were similar between media, independent of whether the embryo transferred was fresh (GB 58.7% vs. G-TL 61.7%) or frozen (GB 64.1% vs. G-TL 60.5%). Live birth rates were also not different. With GB medium, the LBR for fresh and frozen transfers was 54.2% and 53.1%, respectively, as compared with 51.1% and 50%, respectively, with G-TL. CONCLUSION(S): Uninterrupted culture in a time-lapse incubator without medium refreshment was well supported by both media tested. Differences in morphokinetics did not necessarily dictate the superiority of one media over the other. Both pregnancy and LBR were not significantly influenced by choice of culture medium. The euploidy rate was also independent of culture medium.


Subject(s)
Blastocyst/physiology , Culture Media/metabolism , Embryo Culture Techniques , Infertility/therapy , Single Embryo Transfer , Sperm Injections, Intracytoplasmic , Adult , Blastocyst/metabolism , Cryopreservation , Embryo Implantation , Female , Fertility , Humans , Infertility/diagnosis , Infertility/physiopathology , Kinetics , Live Birth , Pregnancy , Pregnancy Rate , Prospective Studies , Single Embryo Transfer/adverse effects , Sperm Injections, Intracytoplasmic/adverse effects , Treatment Outcome
15.
Fertil Steril ; 114(3): 595-600, 2020 09.
Article in English | MEDLINE | ID: mdl-32709380

ABSTRACT

OBJECTIVE: To study the effect of frozen embryo transfer (FET) preparation protocol on incidence of subchorionic hematoma (SCH) and serum hormone levels. DESIGN: Retrospective cohort study. SETTING: University-affiliated fertility center. PATIENT(S): Patients who underwent FET at the New York University Langone Fertility Center. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary outcome was incidence of SCH by protocol in FET cycles. RESULT(S): There were 1,273 FET cycles that met criteria for inclusion. The frequency of SCH was lower in natural compared with programmed cycles (P<.05; relative risk = 0.4 [0.27-0.78]; odds ratio = 0.4 [0.23-0.75]). Serum estrogen level was higher in programmed compared with natural cycles on day of progesterone initiation (P<.001) and cycle day 28 (P<.001). However, serum estrogen levels at the same time points were not associated with formation of SCH in programmed or natural cycles. CONCLUSION(S): This is the first study to evaluate the formation of SCHs by FET protocol type. Our results highlight that high serum estradiol levels do not independently lead to an increase in rate of SCH. Further research must be done to understand other clinical, or perhaps molecular, differences between natural and programmed FET cycle preparations that can be better associated with SCH formation.


Subject(s)
Cryopreservation , Hematoma/epidemiology , Infertility/therapy , Pregnancy Complications/epidemiology , Single Embryo Transfer/adverse effects , Adult , Female , Fertility , Fertilization in Vitro , Hematoma/diagnostic imaging , Humans , Incidence , Infertility/diagnosis , Infertility/physiopathology , New York City/epidemiology , Pregnancy , Pregnancy Complications/diagnostic imaging , Pregnancy Rate , Retrospective Studies , Risk Assessment , Risk Factors , Treatment Outcome , Ultrasonography, Prenatal
16.
Fertil Steril ; 113(5): 990-995, 2020 05.
Article in English | MEDLINE | ID: mdl-32386621

ABSTRACT

OBJECTIVE: To assess whether the calculated difference in endometrial thickness from the end of the estrogen phase to the day of ET (after 6 days of P in hormonally prepared cycles) is associated with ongoing pregnancy rates in euploid frozen ETs (FETs). DESIGN: An observational cohort study. SETTING: Single tertiary care medical center. PATIENT(S): Ultrasound images from 234 hormonally prepared FET cycles were assessed. All the transfers were elective single ETs of a euploid embryo, post-preimplantation genetic testing for aneuploidy (PGT-A). INTERVENTION(S): Ultrasound measurements of peak endometrial thickness at the end of the estrogen phase and again after 6 days of P at the time of ET. MAIN OUTCOME MEASURE(S): Ongoing pregnancy rate in relation to the delta between endometrial thickness at the end of estrogen phase and at the time of ET. RESULT(S): We calculated the ongoing pregnancy rate in cycles where the endometrial lining decreased (compacted) after addition of P by 5%, 10%, 15%, and 20% and demonstrated a significantly higher pregnancy rate after all rates of compaction of the endometrial lining in comparison with cycles where the endometrial lining did not compact. The ongoing pregnancy rate in this cohort, after compaction of 15% or more, was 51.5%, compared with 30.2% in cycles where the endometrial lining did not compact. CONCLUSION(S): There is a significant correlation between endometrial lining compaction and ongoing pregnancy rate in FET cycles of euploid embryos. These findings help to explain why some euploid embryos may fail to implant.


Subject(s)
Embryo Implantation , Endometrium/drug effects , Fertilization in Vitro , Single Embryo Transfer , Adult , Blastocyst/physiology , Endometrium/diagnostic imaging , Female , Fertility Agents/adverse effects , Fertility Agents/therapeutic use , Fertilization in Vitro/adverse effects , Genetic Testing , Humans , Ploidies , Pregnancy , Pregnancy Rate , Preimplantation Diagnosis , Single Embryo Transfer/adverse effects , Time Factors , Treatment Outcome , Ultrasonography
17.
Article in English | MEDLINE | ID: mdl-32047479

ABSTRACT

The number of embryos transferred during an IVF cycle is directly related to the high incidence of multiple births, which is the culprit of perinatal morbidity. Therefore, single fresh embryo transfer (ET) strategy, or freeze-all, followed by a single frozen-thawed embryo transfer (FET) cycle, may dramatically reduce the rate of multiple births, without compromising the cumulative live birth rates (LBRs). A literature review was conducted for all available evidences assessing obstetrics and perinatal outcomes associated with FET compared to fresh ET and natural conception. While studies comparing fresh and FET cycles in normal responders have yielded conflicting results for pregnancy rate, FET was associated with lower risk of prematurity and low birth weight and increased risk of large for gestational age (LGA) and/or macrosomic in singletons, when compared with fresh ET. Macrosomic/LGA births have a higher risk of fetal hypoxia, stillbirth, shoulder dystocia, perineal lacerations, cesarean section, postpartum hemorrhage and neonatal metabolic disturbances at birth. Nonetheless, it seems that other than higher risk of fetal macrosomia, there are additional obstetric complications associated with FET. The relative risk of hypertensive disorders in pregnancy, as well as perinatal mortality were also demonstrated to be increased in FET compared with singletons from fresh ET and natural conception. Therefore, when considering elective freeze-all policy, in addition to LBR and the risk of ovarian hyperstimulation syndrome, physicians should consider the aforementioned increased FET cycles' pregnancy complications, including LGA/ macrosomia, hypertensive disorders of pregnancy, as well as perinatal mortality.


Subject(s)
Cryopreservation/statistics & numerical data , Embryo, Mammalian , Fertilization in Vitro/adverse effects , Fetal Macrosomia/etiology , Infant, Newborn, Diseases/etiology , Birth Weight , Female , Fertilization in Vitro/statistics & numerical data , Fetal Macrosomia/epidemiology , Freezing , Humans , Infant, Newborn , Infant, Newborn, Diseases/epidemiology , Perinatal Mortality , Pregnancy , Pregnancy Outcome/epidemiology , Pregnancy Rate , Risk Factors , Single Embryo Transfer/adverse effects , Single Embryo Transfer/statistics & numerical data
18.
Fertil Steril ; 112(6): 1080-1093.e1, 2019 12.
Article in English | MEDLINE | ID: mdl-31843084

ABSTRACT

OBJECTIVE: To investigate whether the morphodynamic characterization of a euploid blastocyst's development allows a higher prediction of a live birth after single-embryo-transfer (SET). DESIGN: Observational cohort study conducted in two phases: training and validation. SETTING: Private in vitro fertilization centers. PATIENT(S): Euploid blastocysts: 511 and 319 first vitrified-warmed SETs from 868 and 546 patients undergoing preimplantation genetic testing for aneuploidies (PGT-A) in the training and validation phase, respectively. INTERVENTION(S): Data collected from time of polar body extrusion to time of starting blastulation, and trophectoderm and inner-cell-mass static morphology in all embryos cultured in a specific time-lapse incubator with a continuous medium. Logistic regressions conducted to outline the variables showing a statistically significant association with live birth. In the validation phase, these variables were tested in an independent data set. MAIN OUTCOME MEASURE(S): Live births per SET. RESULT(S): The average live birth rate (LBR) in the training set was 40% (N = 207/511). Only time of morulation (tM) and trophectoderm quality were outlined as putative predictors of live birth at two IVF centers. In the validation set, the euploid blastocysts characterized by tM <80 hours and high-quality trophectoderm resulted in a LBR of 55.2% (n = 37/67), while those with tM ≥ 80 hours and a low-quality trophectoderm resulted in a LBR of 25.5% (N = 13/51). CONCLUSION(S): Time of morulation and trophectoderm quality are better predictors of a euploid blastocyst's reproductive competence. Our evidence was reproducible across different centers under specific culture conditions. These data support the crucial role of morulation for embryo development, a stage that involves massive morphologic, cellular, and molecular changes and deserves more investigation.


Subject(s)
Blastocyst/pathology , Fertilization in Vitro , Infertility/therapy , Morula/pathology , Single Embryo Transfer , Time-Lapse Imaging , Adult , Embryo Culture Techniques , Embryo Implantation , Embryonic Development , Female , Fertility , Fertilization in Vitro/adverse effects , Humans , Infertility/diagnosis , Infertility/physiopathology , Kinetics , Live Birth , Middle Aged , Predictive Value of Tests , Pregnancy , Pregnancy Rate , Reproducibility of Results , Risk Factors , Rome , Single Embryo Transfer/adverse effects , Spain , Treatment Outcome
19.
J Assist Reprod Genet ; 36(12): 2459-2469, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31673853

ABSTRACT

PURPOSE: Gestational surrogacy (GS) has been researched in multiple qualitative studies. In contrast, quantitative aspects of the practice are conspicuously understudied. The present article assesses and compares the incidence of GS in the USA and Israel, two industrialized countries that have maintained active commercial surrogacy practice, for over two decades. METHOD: The article is a secondary analysis of GS figures published by the Israeli Parliament's Centre for Research and Information (2018) and by the USA's Centers for Disease Control (2016) and related professional publications. Each dataset is analyzed in reference to the respective country, so as to devise local incidence scores that are then juxtaposed in inter-country comparison. RESULTS: The incidence of GS rises steeply in both countries. Though US surrogates are contracted by local and international, heterosexual and gay, and partnered and single intended parents, the relative incidence of GS is lower in the USA than in Israel, where only local heterosexual couples could contract a gestational surrogate. An exceptionally high rate of multiple births was observed in both settings, suggesting some overlooking of professional recommendations for elective single-embryo transfer. CONCLUSION: GS incidence appears to resemble the ratio between the countries' respective fertility rates. The paper underscores two main risks facing gestational surrogates: the risk of not conceiving and not being paid and the risk of carrying a multiple pregnancy, which is extremely prevalent in GS pregnancies, and sustaining the short- and long-term health complications that are more prevalent in such pregnancies.


Subject(s)
Fertilization in Vitro/adverse effects , Pregnancy, Multiple/physiology , Reproductive Techniques, Assisted/adverse effects , Surrogate Mothers , Female , Heterosexuality/physiology , Humans , Israel/epidemiology , Pregnancy , Single Embryo Transfer/adverse effects , United States/epidemiology , Women's Health
20.
Fertil Steril ; 112(6): 1071-1079.e7, 2019 12.
Article in English | MEDLINE | ID: mdl-31551155

ABSTRACT

OBJECTIVE: To evaluate the benefit of next-generation sequencing (NGS)-based preimplantation genetic testing for aneuploidy (PGT-A) for embryo selection in frozen-thawed embryo transfer. DESIGN: Randomized controlled trial. SETTING: Not applicable. PATIENT(S): Women aged 25-40 years undergoing IVF with at least two blastocysts that could be biopsied. INTERVENTION(S): Randomization for single frozen-thawed embryo transfer with embryo selection based on PGT-A euploid status versus morphology. MAIN OUTCOME MEASURE(S): Ongoing pregnancy rate (OPR) at 20 weeks' gestation per embryo transfer. RESULT(S): A total of 661 women (average age 33.7 ± 3.6 years) were randomized to PGT-A (n = 330) or morphology alone (n = 331). The OPR was equivalent between the two arms, with no significant difference per embryo transfer (50% [137/274] vs. 46% [143/313]) or per intention to treat (ITT) at randomization (41.8% [138/330] vs. 43.5% [144/331]). Post hoc analysis of women aged 35-40 years showed a significant increase in OPR per embryo transfer (51% [62/122] vs. 37% [54/145]) but not per ITT. CONCLUSION(S): PGT-A did not improve overall pregnancy outcomes in all women, as analyzed per embryo transfer or per ITT. There was a significant increase in OPR per embryo transfer with the use of PGT-A in the subgroup of women aged 35-40 years who had two or more embryos that could be biopsied, but this was not significant when analyzed by ITT. CLINICAL TRIAL REGISTRATION NUMBER: NCT02268786.


Subject(s)
Aneuploidy , Blastocyst/pathology , Cryopreservation , Fertilization in Vitro , Genetic Testing , High-Throughput Nucleotide Sequencing , Infertility/therapy , Preimplantation Diagnosis/methods , Single Embryo Transfer , Adult , Australia , Biopsy , Embryo Implantation , Female , Fertility , Fertilization in Vitro/adverse effects , Humans , Infertility/diagnosis , Infertility/physiopathology , North America , Predictive Value of Tests , Pregnancy , Pregnancy Rate , Risk Factors , Single Embryo Transfer/adverse effects , Treatment Outcome , United Kingdom
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