LAUSR

Response: We thank the author for this letter to the Editor, for taking the time to read our manuscript and showing an active interest in our work. We agree with the author that the use of growth hormone in ART has been highly debated and the use of GH in women with poor ovarian reserve has not been shown to increase live birth rates in those women. However, our work studied women who do not meet Bologna criteria and therefore are not characterized by poor ovarian reserve or expected a priori to have a poor response. Moreover, it is the first paper to study outcomes after adjuvant GH in IVF/PGT-A cycles, thus allowing the novel comparison of euploid embryos obtained between cycles in the same patient. We agree that an increase in the number of PGT-A euploid embryos does not necessarily equate to a live birth. However, for patients without a prior biopsied and/or euploid embryo, obtaining even one euploid embryo in a subsequent cycle would increase that patient’s live birth rate significantly from 0% (in the cycle with no euploid embryo for transfer). The studies referenced by the author showing no improvement in live birth rate in the setting of increased number of embryos did not assess the ploidy of those embryos. Certainly, obtaining increasing numbers of aneuploid embryos would not be expected to improve live birth rate. Hence, the assessment of euploid embryos as was reported in our manuscript is the most clinically relevant outcome. Indeed, the goal of our study from the outset was to assess whether adjuvant GH would be associated with an increase in the number of biopsied embryos and euploid embryos. We concur with the author that while an increase in MII oocyte number may seem exciting, that in and of itself does not mean a more successful outcome, and thus, MII number was not a primary outcome in our study. In fact, the difference between the two cycles with respect to number of MII oocytes was not statistically different. However, the number of euploid embryos, our primary outcome, was statistically significant. In response to the author’s comment on euploidy rate, we concur. We did not expect a change in euploidy rate with GH administration as this is likely fixed for each patient. Again, the absolute number of euploid embryos is the clinically relevant outcome because it represents an opportunity at pregnancy where one did not exist in the control cycle in many cases due to no euploid embryos for transfer. The author also cited concerns regarding the patient population of our study. As stated in our manuscript, we excluded all patientsmeeting Bologna POR criteria. Further, we excluded all patients with prior stimulations (i.e., the “control” stimulation was the very first stimulation for that patient). Stimulation protocols were unchanged for each patient between cycles, except for the addition of GH after the first stimulation attempt. The dosing questioned by the author (300 FSH/150 hMG) was only used in 54% of the patients in our manuscript and was based on various factors including patient age and BMI. The author also made mention of the vulnerability of patients and the cost of GH supplementation.We could not agree more that these concerns should be taken into account when considering any clinical intervention. This is a clinical study that was conducted in a state in which there is limited fertility coverage, such that approximately 70% of the patients in the study were completely self-funded. So, we are acutely aware * Winifred Mak [email protected]