Frontiers in Endocrinology (Apr 2022)
Ovarian Reserve and ART Outcomes in Blepharophimosis-Ptosis-Epicanthus Inversus Syndrome Patients With FOXL2 Mutations
- Tingting Meng,
- Tingting Meng,
- Tingting Meng,
- Tingting Meng,
- Tingting Meng,
- Wenzhe Zhang,
- Wenzhe Zhang,
- Wenzhe Zhang,
- Wenzhe Zhang,
- Wenzhe Zhang,
- Rongrong Zhang,
- Rongrong Zhang,
- Rongrong Zhang,
- Rongrong Zhang,
- Rongrong Zhang,
- Jie Li,
- Jie Li,
- Jie Li,
- Jie Li,
- Jie Li,
- Yuan Gao,
- Yuan Gao,
- Yuan Gao,
- Yuan Gao,
- Yuan Gao,
- Yingying Qin,
- Yingying Qin,
- Yingying Qin,
- Yingying Qin,
- Yingying Qin,
- Xue Jiao,
- Xue Jiao,
- Xue Jiao,
- Xue Jiao,
- Xue Jiao,
- Xue Jiao
Affiliations
- Tingting Meng
- Center for Reproductive Medicine, Shandong University, Jinan, China
- Tingting Meng
- Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China
- Tingting Meng
- Shandong Key Laboratory of Reproductive Medicine, Shandong University, Jinan, China
- Tingting Meng
- Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, China
- Tingting Meng
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, China
- Wenzhe Zhang
- Center for Reproductive Medicine, Shandong University, Jinan, China
- Wenzhe Zhang
- Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China
- Wenzhe Zhang
- Shandong Key Laboratory of Reproductive Medicine, Shandong University, Jinan, China
- Wenzhe Zhang
- Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, China
- Wenzhe Zhang
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, China
- Rongrong Zhang
- Center for Reproductive Medicine, Shandong University, Jinan, China
- Rongrong Zhang
- Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China
- Rongrong Zhang
- Shandong Key Laboratory of Reproductive Medicine, Shandong University, Jinan, China
- Rongrong Zhang
- Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, China
- Rongrong Zhang
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, China
- Jie Li
- Center for Reproductive Medicine, Shandong University, Jinan, China
- Jie Li
- Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China
- Jie Li
- Shandong Key Laboratory of Reproductive Medicine, Shandong University, Jinan, China
- Jie Li
- Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, China
- Jie Li
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, China
- Yuan Gao
- Center for Reproductive Medicine, Shandong University, Jinan, China
- Yuan Gao
- Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China
- Yuan Gao
- Shandong Key Laboratory of Reproductive Medicine, Shandong University, Jinan, China
- Yuan Gao
- Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, China
- Yuan Gao
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, China
- Yingying Qin
- Center for Reproductive Medicine, Shandong University, Jinan, China
- Yingying Qin
- Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China
- Yingying Qin
- Shandong Key Laboratory of Reproductive Medicine, Shandong University, Jinan, China
- Yingying Qin
- Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, China
- Yingying Qin
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, China
- Xue Jiao
- Center for Reproductive Medicine, Shandong University, Jinan, China
- Xue Jiao
- Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China
- Xue Jiao
- Shandong Key Laboratory of Reproductive Medicine, Shandong University, Jinan, China
- Xue Jiao
- Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, China
- Xue Jiao
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, China
- Xue Jiao
- Suzhou Research Institute, Shandong University, Jinan, China
- DOI
- https://doi.org/10.3389/fendo.2022.829153
- Journal volume & issue
-
Vol. 13
Abstract
ObjectiveTo characterize the status of ovarian reserve and ART outcomes in BPES women and provide informative reference for clinical diagnosis and treatment.MethodsTwenty-one women with BPES were screened for mutations in the FOXL2 gene and underwent assisted reproductive technology (ART) treatment. Indicators for ovarian reserve and ART outcomes were compared between patients with and without FOXL2 mutations. Additionally, ART outcomes were compared among patients with different subtypes of FOXL2 mutations.ResultsA total of 13 distinct heterozygous variants in the FOXL2 gene were identified in 80.95% of BPES women, including 4 novel mutations with plausible pathogenicity (c.173_175dup, c.481C>T, c.576del and c.675_714del). Compared to non-mutation group, patients with FOXL2 mutations had elevated levels of FSH (P=0.007), decreased AMH levels (P=0.012) and less AFC (P=0.015). They also had worse ART outcomes with large amount of Gn dosage (P=0.008), fewer oocytes (P=0.001), Day3 good quality embryos (P=0.001) and good quality blastocysts (P=0.037), and a higher cancellation rate (P=0.272). High heterogeneity of ART outcomes existed in BPES patients with different FOXL2 mutation types.ConclusionsBPES patients with FOXL2 mutations had diminished ovarian reserve and adverse ART outcomes. The genotype-reproductive phenotype correlations were highly heterogeneous and cannot be generalized. Genetic counseling for fertility planning and preimplantation or prenatal genetic diagnosis to reduce offspring inheritance are recommended.
Keywords
- blepharophimosis-ptosis-epicanthus inversus syndrome (BPES)
- FOXL2
- infertility
- ovarian reserve
- assisted reproductive technology (ART)
