Morphology-based selection from available euploid blastocysts induces male-skewed sex proportion in the offspring

Kulmann, Marcos Iuri Roos; Martello, Carolina Lumertz; Donatti, Luiza Mezzomo; Bös-Mikich, Adriana; Frantz, Nilo

doi:10.1007/s10815-021-02235-9

Cited by 3 publications

(2 citation statements)

References 36 publications

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“…Several studies ( Lou et al., 2020 ; Hu et al., 2021 ) also suggest that high-quality blastocysts are more likely to lead to male infants than poor-quality blastocysts. Roos Kulmann et al. (2021) performed biopsies on 1,254 embryos from 466 PGT-A patients, further confirming that male embryos possibly have higher TE grades.…”

Section: Discussionmentioning

confidence: 76%

Comparison of frozen-thawed embryo transfer strategies for the treatment of infertility in young women: a retrospective study

et al. 2022

PeerJ

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Objective To investigate transfer strategies in the frozen-thawed embryo transfer (FET) cycle. Methods The clinical data of 1,652 FET patients were divided into five groups according to the number and quality of the transferred blastocyst: high-quality single blastocyst group (group A, n = 558), high-quality plus poor-quality double blastocyst group (group B, n = 435), poor-quality double blastocyst group (group C, n = 241), high-quality double blastocyst group (group D, n = 298), and poor-quality single blastocyst group (group E, n = 120). Inter-group comparison analyses of primary conditions, pregnancy outcomes and neonatal outcomes were then performed. Results Group A had the highest embryo implantation rate (67.38%), significantly different from the implantation rates of the other four groups. The gemellary pregnancy rate (1.60%), preterm birth rate (5.58%), neonatal birth weight (3,350g [3,000g, 3,650g]), neonatal birth age (39.57 weeks [38.71, 40.34]), and incidence of low birth weight (7.02%) in group A were different from those in groups B, C, and D, but did not significantly differ from those in group E. Moreover, the proportions of male infants born in groups A (56.86%) and D (59.41%) were significantly higher than those in the other three groups. Double blastocyst transfer (0.528, 95% CI [0.410–0.680], P < 0.001) and high-quality blastocyst transfer (0.609, 95% CI [0.453–0.820], P = 0.001) were found to be protective factors for live birth. In addition, double blastocyst transfer was also the largest risk factor for pregnancy complications (3.120, 95% CI [2.323–4.190], P < 0.001) and neonatal complications (2.230, 95% CI [1.515–3.280], P < 0.001), especially for gemellary pregnancy (59.933, 95% CI [27.298–131.58], P < 0.001) and preterm birth (3.840, 95% CI [2.272–6.489], P < 0.001). Based on the ROC curves, a double blastocyst transfer could predict gemellary pregnancy reliably with a high area under the curve (AUC = 78.53%). Additionally, a double blastocyst transfer could effectively predict a high risk of pregnancy complications (AUC = 65.90%), neonatal complications (AUC = 64.80%) and preterm birth (AUC = 66.20%). Conclusion The live birth rate of frozen-thawed high-quality single blastocyst transfer is lower than that of double high-quality blastocyst transfer, which can significantly increase the embryo implantation rate. High-quality single blastocyst transfer also significantly lowers the risk of gemellary pregnancy, preterm birth, and low birth weight, and can significantly improve maternal and infant outcomes. After weighing the pros and cons of live birth with pregnancy and neonatal complications, the authors believe that high-quality single blastocyst transfer is the optimal FET strategy for young women and is worthy of further clinical application. Despite this recommendation, high-quality single blastocyst transfer can increase the risk of monozygotic twins, as well as significantly increase the proportion of male infants born.

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Section: Discussionmentioning

confidence: 76%

Comparison of frozen-thawed embryo transfer strategies for the treatment of infertility in young women: a retrospective study

et al. 2022

PeerJ

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“…There is evidence that male preimplantation embryos have different developmental trajectories than female embryos ( Avery et al, 1991 ; Valdivia et al, 1993 ; Bernardi and Delouis, 1996 ; Bronet et al, 2015 ; Roos Kulmann et al, 2021 ) and that placental gene expression and DNA methylation are sexually dimorphic ( Martin et al, 2017 ; Mayne et al, 2017 ; Gong et al, 2018 ; Gonzalez et al, 2018 ; Sun et al, 2020 ; Braun et al, 2021 ). Although both male and female concepti are affected by embryo culture with respect to perinatal outcomes, junctional zone overgrowth, pTGC number, and ICR methylation levels compared to controls, we wanted to control for existing sex-specific differences in placental DNA methylation.…”

Section: Resultsmentioning

confidence: 99%

Placental Abnormalities are Associated With Specific Windows of Embryo Culture in a Mouse Model

Vrooman

Rhon‐Calderón

Suri

et al. 2022

Front. Cell Dev. Biol.

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Assisted Reproductive Technologies (ART) employ gamete/embryo handling and culture in vitro to produce offspring. ART pregnancies have an increased risk of low birth weight, abnormal placentation, pregnancy complications, and imprinting disorders. Embryo culture induces low birth weight, abnormal placental morphology, and lower levels of DNA methylation in placentas in a mouse model of ART. Whether preimplantation embryos at specific stages of development are more susceptible to these perturbations remains unresolved. Accordingly, we performed embryo culture for several discrete periods of preimplantation development and following embryo transfer, assessed fetal and placental outcomes at term. We observed a reduction in fetal:placental ratio associated with two distinct windows of preimplantation embryo development, one prior to the morula stage and the other from the morula to blastocyst stage, whereas placental morphological abnormalities and reduced imprinting control region methylation were only associated with culture prior to the morula stage. Extended culture to the blastocyst stage also induces additional placental DNA methylation changes compared to embryos transferred at the morula stage, and female concepti exhibited a higher loss of DNA methylation than males. By identifying specific developmental windows of susceptibility, this study provides a framework to optimize further culture conditions to minimize risks associated with ART pregnancies.

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Does embryo quality at transfer affect obstetric outcomes and placental findings?

Herman

Volodarsky‐Perel

et al. 2023

Human Reproduction

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STUDY QUESTION Do obstetric outcomes and placental findings in pregnancies conceived with IVF vary according to embryo quality? SUMMARY ANSWER Pregnancies following the transfer of lower-quality embryos were associated with a higher rate of low-lying placentas and several adverse placental lesions. WHAT IS KNOWN ALREADY A few studies have shown reduced pregnancy and live births rates with poor-quality embryo transfer, yet with comparable obstetric outcomes. None of these studies included placental analysis. STUDY DESIGN, SIZE, DURATION A retrospective cohort study of 641 deliveries of IVF attained pregnancies between 2009 and 2017 was carried out. PARTICIPANTS/MATERIALS, SETTING, METHODS Live singleton births after IVF with a single blastocyst transfer at a university-affiliated tertiary hospital were included. Excluded were cycles of oocyte recipients and IVM. We compared pregnancies following the transfer of a poor-quality blastocyst (poor-quality group) or a good-quality blastocyst (controls, good-quality group). During the study period, all placentas from complicated and uncomplicated pregnancies were sent to pathology. Primary outcomes were placental findings, including anatomic, inflammatory, vascular malperfusion, and villous maturation lesions, categorized according to the Amsterdam Placental Workshop Group Consensus. Secondary outcomes included obstetric and perinatal outcomes, adjusted for diminished ovarian reserve, fresh versus frozen transfer, and neonatal gender (as indicated by univariable analysis). MAIN RESULTS AND THE ROLE OF CHANCE A total of 132 deliveries in the poor-quality group were compared to 509 controls. A diagnosis of diminished ovarian reserve was more common in the poor-quality group than in the control group (14.3% versus 5.5%, respectively, P < 0.001) and more pregnancies in the poor-quality group were following frozen embryo transfer. After adjustment for confounders, poor-quality embryos were associated with a higher rate of low-lying placentas [adjusted odds ratio (aOR) 2.35, 95% CI 1.02–5.41, P = 0.04] and placentas with a higher rate of villitis of unknown etiology (aOR 2.97, 95% CI 1.17–6.66, P = 0.02), distal villous hypoplasia (aOR 3.78, 95% CI 1.20–11.38, P = 0.02), intervillous thrombosis (aOR 2.41, 95% CI 1.39–4.16, P = 0.001), multiple maternal malperfusion lesions (aOR 1.59, 95% CI 1.06–2.37, P = 0.02), and parenchymal calcifications (aOR 2.19, 95% CI 1.07–4.46, P = 0.03). LIMITATIONS, REASONS FOR CAUTION The study is limited by its retrospective design and the utilization of two grading systems during the study period. In addition, the sample size was limited to detect differences in outcomes of rarer occurrences. WIDER IMPLICATIONS OF THE FINDINGS The placental lesions demonstrated in our study imply an altered immunological response to the implantation of poor-quality embryos. Yet, these findings were not associated with additional adverse obstetric outcomes and merit reaffirmation in a larger cohort. Overall, the clinical findings of our study are reassuring to clinicians and patients for whom the transfer of a poor-quality embryo is necessary. STUDY FUNDING/COMPETING INTEREST(S) No external funding was obtained for this study. The authors declare no conflict of interest, TRIAL REGISTRATION NUMBER N/A.

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Morphology-based selection from available euploid blastocysts induces male-skewed sex proportion in the offspring

Cited by 3 publications

References 36 publications

Comparison of frozen-thawed embryo transfer strategies for the treatment of infertility in young women: a retrospective study

Comparison of frozen-thawed embryo transfer strategies for the treatment of infertility in young women: a retrospective study

Placental Abnormalities are Associated With Specific Windows of Embryo Culture in a Mouse Model

Does embryo quality at transfer affect obstetric outcomes and placental findings?

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