Maternal and obstetric outcomes following the transfer of embryos warmed with fatty acid-supplemented solutions.

BACKGROUND: Vitrification procedures decrease intracytoplasmic lipid content and impair developmental competence. Adding fatty acids (FAs) to the warming solution has been shown to recover the lipid content of the cytoplasm and improve developmental competence and pregnancy outcomes. However, the influence of the FA supplementation on live birth rates after embryo transfers and perinatal outcomes remains unknown. In the present study, we examined the influence of FA-supplemented warming solutions on live birth rates, pregnancy complications, and neonatal outcomes after single vitrified-warmed cleavage-stage embryo transfers (SVCTs). METHODS: The clinical records of 701 treatment cycles in 701 women who underwent SVCTs were retrospectively analyzed. Vitrified embryos were warmed using solutions (from April 2022 to June 2022, control group) or FA-supplemented solutions (from July 2022 to September 2022, FA group). The live birth rate, pregnancy complications, and perinatal outcomes were compared between the control and FA groups. RESULTS: The live birth rate per transfer was significantly higher in the FA group than in the control group. Multivariate logistic regression analysis further demonstrated a higher probability of live births in the FA group than in the control group. Miscarriage rates, the incidence and types of pregnancy complications, the cesarean section rate, gestational age, incidence of preterm delivery, birth length and weight, incidence of low birth weight, infant sex, and incidence of birth defects were all comparable between the control and FA groups. Multivariate logistic regression analysis further demonstrated no adverse effects of FA-supplemented warming solutions. CONCLUSIONS: FA-supplemented warming solutions improved live birth rates after SVCTs without exerting any adverse effects on maternal and obstetric outcomes. Therefore, FA-supplemented solutions can be considered safe and effective for improving clinical outcomes and reducing patient burden.

Comparison of 1-year cumulative live birth and perinatal outcomes following single blastocyst transfer with or without preimplantation genetic testing for aneuploidy: a propensity score-matched study.

PURPOSE: We evaluated whether preimplantation genetic testing for aneuploidy (PGT-A) could increase the cumulative live birth rate (CLBR) in patients with recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL). METHODS: The clinical records of 7,668 patients who underwent oocyte retrieval (OR) with or without PGT-A were reviewed for 365 days and retrospectively analyzed. Using propensity score matching, 579 patients in the PGT-A group were matched one-to-one with 7,089 patients in the non-PGT-A (control) group. Their pregnancy and perinatal outcomes and CLBRs were statistically compared. RESULTS: The live birth rate per single vitrified-warmed blastocyst transfers (SVBTs) significantly improved in the PGT-A group in all age groups (P < 0.0002, all). Obstetric and perinatal outcomes were comparable between both groups regarding both RIF and RPL cases. Cox regression analysis demonstrated that in the RIF cases, the risk ratio per OR was significantly lower in the PGT-A group than in the control group (P = 0.0480), particularly in women aged < 40 years (P = 0.0364). However, the ratio was comparable between the groups in RPL cases. The risk ratio per treatment period was improved in the PGT-A group in both RIF and RPL cases only in women aged 40-42 years (P = 0.0234 and P = 0.0084, respectively). CONCLUSION: Increased CLBR per treatment period was detected only in women aged 40-42 years in both RIF and RPL cases, suggesting that PGT-A is inappropriate to improve CLBR per treatment period in all RIF and RPL cases.

Association between endometrial thickness before ovulation, live birth, and placenta previa rates in clomiphene citrate-treated cycles.

BACKGROUND: Although a recent study reported that the pregnancy outcomes in the first trimester were more correlated with endometrial thickness on the day of the trigger than with endometrial thickness on the day of single fresh-cleaved embryo transfer, it remains unclear whether endometrial thickness on the day of the trigger can predict live birth rate after a single fresh-cleaved embryo transfer. OBJECTIVE: This study aimed to examine whether endometrial thickness on the trigger day is associated with live birth rates and whether modifying the single fresh-cleaved embryo transfer criteria to reflect endometrial thickness on the trigger day improved the live birth rate and reduced maternal complications in a clomiphene citrate-based minimal stimulation cycle. STUDY DESIGN: This was a retrospective study of the outcomes of 4440 treatment cycles of women who underwent single fresh-cleaved embryo transfer on day 2 of the retrieval cycle. From November 2018 to October 2019, single fresh-cleaved embryo transfer was performed when endometrial thickness on the day of single fresh-cleaved embryo transfer was ≥8 mm (criterion A). From November 2019 to August 2020, single fresh-cleaved embryo transfer was conducted when endometrial thickness on the day of the trigger was ≥7 mm (criterion B). RESULTS: A multivariate logistic regression analysis revealed that increased endometrial thickness on the trigger day was significantly associated with an improvement in the live birth rate after single fresh-cleaved embryo transfer (adjusted odds ratio, 1.098; 95% confidence interval, 1.021-1.179). The live birth rate was significantly higher in the criterion B group than in the criterion A group (22.9% and 19.1%, respectively; P=.0281). Although endometrial thickness on the day of single fresh-cleaved embryo transfer was sufficient, the live birth rate tended to be lower when endometrial thickness on the trigger day was <7.0 mm than when endometrial thickness on the day of the trigger was ≥7.0 mm. The risk for placenta previa was reduced in the criterion B group when compared with the criterion A group (4.3% and 0.6%, respectively; P=.0222). CONCLUSION: This study demonstrated an association of decreased endometrial thickness on the trigger day with low birth rate and a high incidence of placenta previa. A modification of the criteria for a single fresh-cleaved embryo transfer based on endometrial thickness may improve pregnancy and maternal outcomes.

Endometrial preparation and maternal and obstetrical outcomes after frozen blastocyst transfer.

BACKGROUND: Two types of endometrial preparation protocols are used for frozen embryo transfers in current practice: hormone replacement and the natural cycle. Endometrial preparation in the natural cycle reportedly increases the chances of live birth and decreases early pregnancy loss compared with that in the hormone replacement cycle. However, the influence of endometrial preparation on maternal and neonatal health remains unclear. OBJECTIVE: This study aimed to investigate whether the differences between hormone replacement cycle and natural cycle influence perinatal outcomes and risk of congenital anomalies in frozen-thawed blastocyst transfer fetuses or births. STUDY DESIGN: Perinatal outcomes and congenital abnormalities were compared between the natural and hormone replacement cycles. According to the timing of ovulation, frozen-thawed blastocyst transfers in the natural cycle were classified into 2 patterns: on day 4.5 (ovulation 4.5) or day 5 (ovulation 5.0) after ovulation. When the serum luteinizing hormone level was not increased on the day of the trigger, a single vitrified-warmed blastocyst transfer was performed on day 7 after the trigger (ovulation 5.0). When the luteinizing hormone level was slightly increased on the day of trigger, single vitrified-warmed blastocyst transfer was performed on day 6 after the trigger (ovulation 5.0). In total, 67,018 cycles (ovulation 4.5, 29,705 cycles; ovulation 5.0, 31,995 cycles; hormone replacement, 5318 cycles) of frozen-thawed blastocyst transfer between January 2008 and December 2017 at Kato Ladies Clinic were retrospectively analyzed. During the study period, embryo cryopreservation was performed using a vitrification method in all cycles. RESULTS: Hormone replacement cycles were associated with a higher occurrence of hypertensive disorders of pregnancy (adjusted odds ratio, 2.16; 95% confidence interval, 1.66-2.81) and placenta accreta (adjusted odds ratio, 4.14; 95% confidence interval, 1.64-10.44) compared with the natural cycle. The risks of cesarean delivery (adjusted odds ratio, 1.93; 95% confidence interval, 1.78-2.18), preterm birth (adjusted odds ratio, 1.55; 95% confidence interval, 1.25-1.93), and low birthweight (adjusted odds ratio, 1.42; 95% confidence interval, 1.18-1.73) were also higher for hormone replacement cycles. No significant difference in the risk of congenital anomalies was observed between the 2 cycles. CONCLUSION: The risk of hypertensive disorders of pregnancy, placenta accreta, cesarean delivery, preterm delivery, and low birthweight was higher in hormone replacement cycles than in natural cycles, whereas the risk of congenital anomalies was similar between both cycles. Further follow-up is needed to investigate these risks and to explore alternative endometrial preparation methods.

Maternal and obstetric outcomes are influenced by developmental stage and cryopreservation of transferred embryos after clomiphene citrate-based minimal stimulation IVF.

STUDY QUESTION: Is the embryo transfer (ET) method associated with maternal and perinatal outcomes after minimal stimulation IVF using clomiphene citrate (CC)? SUMMARY ANSWER: The incidence of pregnancy complications and adverse perinatal outcomes was influenced by the developmental stage (cleavage versus blastocyst stages) and cryopreservation (fresh versus vitrified) of the transferred embryos. WHAT IS KNOWN ALREADY: Pregnancies resulting from IVF are associated with higher risks of adverse perinatal outcomes compared to natural conceptions; therefore, the next focus in reproductive medicine should be to assess whether these increased risks are attributable to IVF. Pregnancy complications and perinatal outcomes should be considered in addition to pregnancy outcomes when selecting the ET method, however, studies that describe the influence of transfer methods on perinatal and maternal outcomes are limited. STUDY DESIGN SIZE DURATION: This study retrospectively analysed a large single-centre cohort. The clinical records of 36 827 women who underwent oocyte retrieval (during a CC-based minimal stimulation cycle) followed by their first ET at the fertility treatment centre between January 2008 and December 2017 were retrospectively analysed. The patients underwent a single fresh cleavage-stage ET (SFCT), single vitrified-warmed cleavage-stage ET (SVCT) or single vitrified-warmed blastocyst transfer (SVBT). This study only included one cycle per patient. PARTICIPANTS/MATERIALS SETTING METHODS: Oocyte retrieval was performed following CC-based minimal ovarian stimulation. The embryos were transferred 2-3 days after retrieval or vitrified at the cleavage or blastocyst stage. The vitrified embryos were then warmed and transferred within the natural cycles. Pregnancy complications and perinatal outcomes were stratified according to the transfer methods used. Multivariate logistic regression analysis was performed to evaluate the effect of ET methods on the prevalence of pregnancy complications and congenital anomalies. MAIN RESULTS AND THE ROLE OF CHANCE: The rates of clinical pregnancy and delivery were significantly different among the groups. We analysed pregnancy complications in 7502 singleton births (SFCT, 3395 cycles; SVCT, 586 cycles; and SVBT, 3521 cycles). Multivariate logistic regression analysis revealed that the adjusted odds ratio (AOR) for hypertensive disorders in pregnancy was significantly lower in the SVBT group than in the SFCT group [AOR, 0.72; 95% CI, 0.56-0.92]. The AOR for low-lying placenta was lower in the SVBT group than in the SFCT group (AOR, 0.34; 95% CI, 0.19-0.60). The AOR for placenta previa was lower in the SVCT and SVBT groups than in the SFCT group (AOR, 0.21; 95% CI, 0.07-0.58 versus AOR, 0.53; 95% CI, 0.38-0.75, respectively). A total of 7460 follow-up data on neonatal outcomes was analysed. The AOR for preterm delivery was lower in the SVBT group than in the SFCT group (AOR, 0.78; 95% CI, 0.64-0.94). The AOR for low birthweight was significantly lower after SVCT and SVBT than after SFCT (AOR, 0.68; 95% CI, 0.46-0.98 versus AOR, 0.57; 95% CI, 0.48-0.66, respectively). The AOR for small for gestational age was lower in the SVCT and SVBT groups than in the SFCT group (AOR, 0.68; 95% CI, 0.46-0.98 versus AOR, 0.44; 95% CI, 0.36-0.55, respectively). The AOR for large for gestational age babies was higher in the SVBT group than in the SFCT group (AOR, 1.88; 95% CI, 1.62-2.18). The incidence of each congenital anomaly was similar among the groups. LIMITATIONS REASONS FOR CAUTION: The study data were collected through self-reported parental questionnaires on maternal and neonatal outcomes. Our findings were not compared with the incidence of pregnancy complications and congenital anomalies in natural pregnancies. Furthermore, this study was retrospective in nature; therefore, further studies are required to ascertain the generalizability of these findings to other clinics with different protocols and/or different patient demographics. WIDER IMPLICATIONS OF THE FINDINGS: This study demonstrated reassuring outcomes for SVBT (in terms of a lower incidence of pregnancy complications) compared to SFCT. Our findings provide valuable knowledge that will help improve perinatal and maternal outcomes in CC-based stimulation and inform couples of the possible benefits and risks of each type of ET method. STUDY FUNDING/COMPETING INTERESTS: This research did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Analysis of clinical factors and reasons that influence the disposition of cryopreserved embryos in Japanese patients with infertility treated in our clinic.

AIM: To investigate the clinical factors and factors that affect the decisions regarding storage of cryopreserved embryos obtained using assisted reproductive technology. METHODS: Clinical characteristics affecting the decisions regarding cryopreserved embryos were analyzed in 5724 Japanese couples who underwent in vitro fertilization (IVF) or intra-cytoplasmic sperm insemination (ICSI) and embryo transfer over 4 years since April 2015 at our clinic. Statistical analysis was carried out using JMP software. RESULTS: The number of oocytes retrievals and embryos stored, outcomes and number of children, and age of the female patients and male partners were related to the decision-making regarding cryopreserved embryos. Childbearing and no wish for another child were the major reasons for discontinuing embryo storage. The number of oocytes retrievals and embryos in storage, age of the female patients, and sex of the child were independently associated with this decision-making in 2682 patients with a single child. Women with male children were more likely to choose discontinuation of embryo storage than those with female children. CONCLUSION: Already having a child and not wishing for further treatment due to age along with the presence of a male child affect the decision to continue or discontinue embryo storage in Japanese patients with infertility.

Endometrial thickness on the day of the LH surge: an effective predictor of pregnancy outcomes after modified natural cycle-frozen blastocyst transfer.

STUDY QUESTION: Can the endometrial thickness (EMT) on the day of the LH surge predict pregnancy outcomes after single vitrified-warmed blastocyst transfers (SVBTs) in modified natural cycles? SUMMARY ANSWER: Decreased EMT on the day of the LH surge is associated with older female age and a shortened proliferation phase and may be associated with low live birth and high chemical pregnancy rates. WHAT IS KNOWN ALREADY: The relation between EMT on the day of embryo transfer (ET) and pregnancy outcomes remains controversial; although numerous studies reported an association between decreased EMT on the day of ET and a reduced likelihood of pregnancy, recent studies demonstrated that the EMT on the day of ET had limited independent prognostic value for pregnancy outcomes after IVF. The relation between EMT on the day of the LH surge and pregnancy outcomes after SVBT in modified natural cycles is currently unknown. STUDY DESIGN SIZE DURATION: In total, 808 SVBTs in modified natural cycles, performed from November 2018 to October 2019, were analysed in this retrospective cohort study. Associations of EMT on the days of the LH surge with SVBT and clinical and ongoing pregnancy rates were statistically evaluated. Clinical and ongoing pregnancy rates were defined as the ultrasonographic observation of a gestational sac 3 weeks after SVBTs and the observation of a foetal heartbeat 5 weeks after SVBTs, respectively. Similarly, factors potentially associated with the EMT on day of the LH surge, such as patient and cycle characteristics, were investigated. PARTICIPANTS/MATERIALS SETTING METHODS: The study includes IVF/ICSI patients aged 24-47 years, who underwent their first SVBT in the study period. After monitoring follicular development and serum hormone levels, ovulation was triggered via a nasal spray containing a GnRH agonist. After ovulation was confirmed, SVBTs were performed on Day 5. The EMT was evaluated by transvaginal ultrasonography on the day of the LH surge and immediately before the SVBT procedure. MAIN RESULTS AND THE ROLE OF CHANCE: Of the original 901 patients, 93 who were outliers for FSH or proliferative phase duration data were excluded from the analysis. Patients were classified according to quartiles of EMT on day of the LH surge, as follows: EMT < 8.1 mm, 8.1 mm ≤ EMT < 9.1 mm, 9.1 mm ≤ EMT < 10.6 mm and EMT ≥ 10.6 mm. Decreased EMT on day of the LH surge was associated with lower live birth (P = 0.0016) and higher chemical pregnancy (P = 0.0011) rates. Similarly, patients were classified according to quartiles of EMT on day of the SVBT, as follows: EMT < 9.1 mm, 9.1 mm ≤ EMT < 10.1 mm, 10.1 mm ≤ EMT < 12.1 mm and EMT ≥ 12.1 mm. A decreased EMT on the day of SVBT was associated with a lower live birth rate (P = 0.0095) but not chemical pregnancy rate (P = 0.1640). Additionally, multivariate logistic regression analysis revealed a significant correlation between EMT on day of the LH surge and ongoing pregnancy; however, no correlation was observed between EMT on the day of SVBT and ongoing pregnancy (adjusted odds ratio 0.952; 95% CI, 0.850-1.066; P = 0.3981). A decreased EMT on day of the LH surge was significantly associated with greater female age (P = 0.0003) and a shortened follicular/proliferation phase (P < 0.0001). LIMITATIONS REASONS FOR CAUTION: The data used in this study were obtained from a single-centre cohort; therefore, multi-centre studies are required to ascertain the generalisability of these findings to other clinics with different protocols and/or patient demographics. WIDER IMPLICATIONS OF THE FINDINGS: This is the first report demonstrating a significant correlation between EMT on day of the LH surge and pregnancy outcomes after frozen blastocyst transfer in modified natural cycles. Our results suggest that EMT on day of the LH surge may be an effective predictor of the live birth rate. STUDY FUNDING/COMPETING INTERESTS: This study was supported by resources from the Kato Ladies Clinic. The authors have no conflicts of interest to declare.