Abstract
Introduction
We wish to report the first live births from genetically screened human euploid blastocysts obtained by uterine lavage. The embryos transferred to infertile women were previously obtained using a novel fully automated uterine lavage catheter and fluid recovery device developed for this indication. The objective of this portion of the research was to confirm embryo implantation and live births with these unique in vivo conceived blastocysts obtained by uterine lavage.
Methods
In vivo conceived embryos recovered by uterine lavage 5 days after intrauterine insemination were available for embryo donation. In vivo embryos were the result of prior controlled ovarian stimulation cycles in oocyte donors and intrauterine insemination with donor sperm. An observational case series of nine embryo transfer procedures was performed at an outpatient fertility center. One to two embryos were transferred to eight infertile women since one woman had two separate embryo transfer procedures.
Results
Nine embryo transfer procedures were performed with 14 blastocysts in eight women resulting in a blastocyst implantation rate of 36% (5/14) and live birth rate of 44% (4/9). Five infants have been born from the four delivered pregnancies with one set of twins.
Conclusions
This is the first report of live births from genetically screened human euploid blastocysts obtained by uterine lavage. The nonsurgical uterine lavage office procedure represents the only current approach to obtain in vivo conceived embryos and can provide a benchmark for comparison to standard in vitro cultured blastocysts. Live births of in vivo conceived blastocysts represent the validation that the nonsurgical uterine lavage procedure allows simplified access to naturally conceived embryos without performing the surgical procedure of an oocyte aspiration. Owing to its simplicity, uterine lavage may be useful in screening embryos for preimplantation genetic testing for aneuploidy in fertile and infertile couples.
Trial Registration Number: ClinicalTrials.gov (Identifier NCT03426007).
Plain Language Summary
The overall goal of this research was to develop a procedure that would allow collection of naturally conceived human embryos and compare them to embryos that result from the standard process of in vitro fertilization (IVF). IVF is a procedure where eggs are surgically removed from the ovaries and fertilized with sperm in a laboratory. Embryos from IVF are cultured for 3–7 days before they are placed back into a woman’s uterus to establish a pregnancy. Uterine lavage is a different procedure where the sperm fertilizes an egg in the normal process of conception and the uterus is rinsed with fluid to recover the embryo before implantation. The embryos reported in this study were the first to be obtained in over 30 years owing to many improvements in the overall uterine lavage procedure. Until our initial study findings reported in 2020, the vast majority of information on embryo development was based on embryos fertilized and cultured in a laboratory. Our prior report of embryos obtained by uterine lavage compared with IVF embryos from the same women demonstrated a significantly better appearance of the embryos recovered by lavage. This current report documents the first live births from these genetically screened naturally conceived human embryos. The live births provide evidence that uterine lavage allows ready access to normal embryos without performing the surgical procedure IVF. Owing to the simplicity of uterine lavage, the procedure may improve access to genetic testing of embryos before pregnancy.
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References
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Acknowledgements
The authors thank all participants for their involvement in this reported clinical case series. The authors also thank the embryology, nursing, and office staff of the Punta Mita Fertility Center for their assistance in conducting this research and subsequent clinical care.
Funding
Cryopreserved human euploid blastocysts were available for embryo transfer to infertile couples from research supported by Previvo Genetics, Inc. Each subsequent embryo transfer procedure was a part of the clinical care of the infertile intended parent and there was no financial support for the embryo transfer procedures. The funding for the journal’s Rapid Service fee was paid by Butterfly Biosciences, Inc., who acquired the assets of Previvo Genetics in September 2021.
Author Contributions
All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Sam Najmabadi, José L. Rivas, Alexander Nadal, Santiago Munné and Steven T. Nakajima. The first draft of the manuscript was written by Steven T. Nakajima and all the authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Prior Presentation
Presented in part at the 76th Annual Meeting of the American Society for Reproductive Medicine, Virtual Meeting, Poster P-141, October 17, 2020. Fertil Steril 2020;114:e165.
Disclosures
Uterine lavage and embryo transfer procedures were performed when the authors had the following relationships with Previvo Genetics, Inc. Sam Najmabadi was a co-author on a non-provisional patent application owned by Previvo and held stock options in Previvo. Marlane J. Angle and Steven T. Nakajima reported consulting fees from Previvo. Marlane J. Angle, Santiago Munné, Sandra A. Carson, John E. Buster and Steven T. Nakajima were members of the Previvo Scientific Advisory Board (SAB) and held stock options in Previvo. Santiago Munné and John E. Buster were members of the Previvo Board of Directors. Alexander Nadal was an employee of Previvo. José L. Rivas and Ercan Bastu had no conflicts to disclose. Butterfly Biosciences, Inc. acquired the assets of Previvo in September 2021. Sam Najmabadi, José L. Rivas, Marlane J. Angle, Alexander Nadal, Santiago Munné and Steven T. Nakajima hold stock options in Butterfly. Sam Najmabadi, Marlane J. Angle, Santiago Munné and Steven T. Nakajima are members of the Butterfly SAB. Sam Najmabadi, Santiago Munné and Steven T. Nakajima are members of the Butterfly Board of Directors. Alexander Nadal is an employee of Butterfly. Ercan Bastu, Sandra A. Carson and John E. Buster have no conflicts to disclose.
Compliance with Ethics Guidelines
In vivo conceived embryos obtained from prior uterine lavage procedures were collected in accordance with the ethical guidelines approved by the Ministry of Health of the State of Nayarit, Mexico (Servicios de Salud de Nayarit) and the Western Institutional Review Board, USA (Study #1176044). This research trial was conducted in accordance with the Declaration of Helsinki and was registered with ClinicalTrials.gov (Identifier NCT03426007). All subjects gave their written informed consent to participate in the original study. Both oocyte and sperm donors specifically gave their written consent for any embryo recovered to be donated to research and potential embryo donation to an infertile couple. All recipient couples gave their written permission to analyze and publish the outcome of their therapy in an aggregate form.
Data Availability
The original data associated with the collection of this in vivo conceived blastocyst set is previously published [1, 2].
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Najmabadi, S., Rivas, J.L., Angle, M.J. et al. Human Uterine Lavage: First Live Births from In Vivo Conceived Genetically Screened Blastocysts. Adv Ther 40, 2534–2541 (2023). https://doi.org/10.1007/s12325-023-02486-1
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DOI: https://doi.org/10.1007/s12325-023-02486-1