Abstract
Purpose
Spontaneous oocyte activation (SOA) is a recently classified phenomenon characterized by the presence of a single pronucleus immediately following oocyte retrieval, without the apparent involvement of sperm. SOA currently remains poorly understood in humans, with no clear genetic or pathological factor(s). Herein, we report two separate cases of recurrent spontaneous oocyte activation, investigating potential avenues to identify causative etiology.
Methods
Two patients with several cycles with SOA have undergone further genetic and embryologic investigation to reveal underlying causes for SOA and provide a treatment if possible.
Results
One case was a patient with recurrent pregnancy loss and the other was diagnosed as unexplained infertility. In the first case, 61 out of 69 oocytes retrieved exhibited SOA in five cycles while in the second case 44 out of 49 oocytes exhibited SOA in five cycles. Oocytes were injected with sperm; embryo development and presence of paternal contribution were investigated. No pregnancy is ensued following embryo transfer in both patients. Time-lapse imaging of embryogenesis from the second case did not reveal even momentary second pronucleus appearance. We also performed clinical whole exome sequencing for both patients but did not identify any disease-causing variant.
Conclusion
Patients with SOA suffer from infertility. Our results indicate that more investigation is required to understand the etiology of SOA in humans concentrating on the molecular mechanisms that underpin regulation of oocyte activation and calcium dynamics need to be investigated to fully understand, and perhaps in the future rectify, recurrent SOA.
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SC and FA conceived the study. SC and JK wrote the manuscript. KA and MA recruited the patients and collected data. WQ and SM performed the experiments. All authors contributed to the article and approved the submitted version.
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Supplementary file1 (AVI 2144 KB)
10815_2022_2435_MOESM2_ESM.jpg
Figure S1. Exome was performed on index patients from case 1 and 2. Filtering strategy starting from larger to smaller circles; Total number of variants=>Homozygous variants=>Coding/Splicing=>Absent in gnomAD and local database=>Predicted deleterious in silico=>Relevant biology (JPG 110 KB)
Supplementary Video 1. Development of embryo generated from the spontaneously activated oocyte following ICSI. Although STR analysis showed paternal contribution, no other pronucleus was seen. (AVI 18404 KB)
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Coskun, S., Maddirevula, S., Awartani, K. et al. Recurrent spontaneous oocyte activation causes female infertility. J Assist Reprod Genet 39, 675–680 (2022). https://doi.org/10.1007/s10815-022-02435-x
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DOI: https://doi.org/10.1007/s10815-022-02435-x