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Review
. 2021 Oct 28;14(1):143.
doi: 10.1186/s13048-021-00900-2.

Confrontment and solution to gonadotropin resistance and low oocyte retrieval in in vitro fertilization for type I BPES: a case series with review of literature

Yiqi Yu  1 , Mengxia Ji  1 , Weihai Xu  1 , Ling Zhang  1 , Ming Qi  2 , Jing Shu  3
Affiliations
Review

Confrontment and solution to gonadotropin resistance and low oocyte retrieval in in vitro fertilization for type I BPES: a case series with review of literature

Yiqi Yu et al. J Ovarian Res. .

Abstract

Background: FOXL2 mutations in human cause Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES). While type II BPES solely features eyelid abnormality, type I BPES involves not only eyelid but also ovary, leading to primary ovarian insufficiency (POI) and female infertility. Current mainstream reproductive option for type I BPES is embryo or oocyte donation. Attempts on assisted reproductive technology (ART) aiming biological parenthood in this population were sparse and mostly unsuccessful.

Case presentation: Two Chinese type I BPES patients with low anti-müllerian hormone (AMH) and elevated follicle stimulating hormone (FSH) presented with primary infertility in their early 30s. Genetic studies confirmed two heterozygous duplication mutations that were never reported previously in East Asian populations. They received in vitro fertilization (IVF) treatment and both exhibited resistance to gonadotropin and difficulty in retrieving oocytes in repeated cycles. Doubled to quadrupled total gonadotropin doses were required to awaken follicular response. Patient 1 delivered a baby girl with the same eyelid phenotype and patient 2 had ongoing live intrauterine pregnancy at the time of manuscript submission.

Conclusions: This is the second reported live birth of biological offspring in type I BPES patients, and first success using IVF techniques. It confirmed that ART is difficult but feasible in type I BPES. It further alerts clinicians and genetic counsellors to type female BPES patients with caution in view of the precious and potentially narrowed reproductive window.

Keywords: and epicanthus inversus syndrome”; ptosis; “Blepharophimosis; “FOXL2”; “Gonadotropin resistance”; “In vitro fertilization”; “Infertility”.

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Conflict of interest statement

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of this article.

Figures

Fig. 1
Fig. 1
Follicular growth under controlled ovarian hyperstimulation (COH) showing the relationship between serum FSH level and follicular response as well as the corresponding serum estradiol level. Follicles are divided into 5 groups: ≤5 mm, 6-9 mm, 10-14 mm, 15-19 mm, ≥20 mm. Percentage of each group is shown. S1 = Day 1 of hyperstimulation. a Patient 1's second COH cycle; b Patient 2's first COH cycle, note that no exact estradiol reading was recorded on S20 because the corresponding serum sample was not diluted; c Patient 2's second COH cycle
Fig. 2
Fig. 2
Positions of mutations detected in the two patients. Purple region: forkhead domain (FHD); Orange region: polyalanine tract (PAT); Blue region: the rest of coding region. Pathogenic or likely-pathogenic mutations submitted in ClinVar were summarized, presenting as short vertical lines: black line = point mutation; white line = mutation resulting in deletion or duplication
Fig. 3
Fig. 3
Pedigrees and Sanger sequencing of patients and their relatives. a Sanger sequencing for patient 1 and her parents is demonstrated. b Sanger sequencing for patient 2 and her mother is demonstrated
See this image and copyright information in PMC

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