Trophectoderm biopsy—perhaps not such a benign intervention

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Authors:

Catherine E. Gordon, M.D., Catherine Racowsky, Ph.D.

Abstract:

Reflections on "Trophectoderm biopsy reduces the level of serum β-hCG in early pregnancy" by Lu et al.

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Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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Reply to “Trophectoderm biopsy—perhaps not such a benign intervention”

Dear Dr. Catherine Gordon and Dr. Catherine Racowsky,

Thank you very much for your comment on our paper titled “Trophectoderm biopsy reduces the level of serum β-HCG in early pregnancy”.

We totally agreed with you that it would have been more informative if we had compared the trends in β-hCG rise for each of the two groups, based on at least two successive measurements. However, most of the patients had no more than one measurement in our hospital. It is impossible for us to analyze the trend, but in the future, we can collect more data to analyze it.

The minimum β-hCG values of the biosied group and the control group with live births were 150.4 mIU/mL and 127.6 mIU/mL respectively, which might indicate that pregnancies with relatively low β-hCG values still have a chance to progress to live births. We need to emphasize that the β-hCG values were not normally distributed for each group, therefore, interquartile ranges, instead of the standard deviations, were presented in the brackets following the β-hCG values. Of course, significantly overlap did exist between two groups, which still raises questions regarding the sensivity and specificity of a lower β-hCG cut-off value to predict a successful pregnancy following trophectoderm biopsy.

As you mentioned, there were more programmed embryo transfer cycles in the biopsy group as compared to the control group. Whether increased use of a programmed endometrial preparation in the biopsy group had any impact on b-hCG levels remains to be a question. We also noticed this difference in endometrial preparation protocols, therefore, we analyzed it in the generalized linear regression analyses. We found that there was no staticstially significant impact of enometrial preparation protocol on the β-hCG values.

It was a very good question whether assisted hatching may affect β-hCG levels. Theoretically, assisted hatching may allow embryo implantation early. All embryos in the biopsy group underwent assisted hatching to facilitate the biopsy procedure, while hatching was not performed in the control group. Therefore, we may expect a greater difference in the levels of β-hCG between the two groups if the control embryos had also undergone assisted hatching. However, shrinkage by laser was performed in all embryos in the control group before the vitrification procedure, which inevitablely crack the zona pellucida. Although the hole size in the biopsy group was bigger than the cleft in the control group, it would be hard to analyze the impact of this difference.

We agreed with you that a larger dataset may be more informative to determine whether a lower β-hCG cut-off value predicts a successful pregnancy following trophectoderm biopsy. As acknowledged by you and us, the results must be interpreted with caution because of the relatively small numbers of livebirths analyzed. Currently, a National Key Reseach and Development Program regarding safety issues of children born after all types of assisted reproductive technology is in progress in China. We expect more solid data based on this national investigation in the near future.

 Our study was supported by: " National Key Research and Development Program (2018YFC1003102); Guangzhou Science and Technology Project(201804020087); National Natural Science Foundation of China(81771588)".

 Thank you and best regards.
Manman Lu, Yanwen Xu,

Corresponding author:
Name: Yanwen Xu
E-mail: xuyanwen@mail.sysu.edu.cn                                                      Telephone number:86-13682213000