OBJECTIVE Evaluate effects of a Lynch syndrome universal screening protocol in newly diagnosed endometrial cancers on subsequent genetic counseling (GC) and germline testing (GT) referral and acceptance rates. METHODS We performed a retrospective cohort study of women who underwent a hysterectomy for endometrial cancer at Barnes Jewish Hospital in St. Louis, MO between 1/1/2011 and 12/31/2013 (n=637). An immunohistochemistry-based (IHC) universal screening protocol for Lynch syndrome was initiated on 12/17/2012. The cohorts consisted of women presenting prior to (Pre Em-USP; n=395) and those presenting following (Em-USP; n=242) initiation of the universal screening protocol. GC and GT referrals were based on risk factors and/or IHC results. Comparisons were made using the Fisher’s exact test and the Kruskal-Wallis test. RESULTS A greater proportion of individuals in the Em-USP cohort underwent GT than in Pre Em-USP (9.1% vs 4.8%, p<0.05). Of individuals with an IHC screening result suggestive of LS, those within the Em-USP cohort were significantly more likely to accept GC compared to those in the Pre-Em-USP cohort (95% vs 64%, p=0.02). Specifically within the Em-USP cohort, patients referred to GC due to a concerning IHC screening result, versus those who were referred based on other risk factors, had a higher counseling acceptance rate (95% vs 61%, p=0.03) and underwent genetic testing more readily (76% vs 30%, p<0.001). CONCLUSIONS Implementation of an IHC-based universal screening protocol for LS in endometrial cancer leads to higher acceptance of genetic counseling and higher rates of genetic testing compared to referral based on risk factors alone.

has been reviewed by the Editorial Board and by special expert referees. Although it is judged not acceptable for publication in Obstetrics & Gynecology in its present form, we would be willing to give further consideration to a revised version. If you wish to consider revising your manuscript, you will first need to study carefully the enclosed reports submitted by the referees and editors. Each point raised requires a response, by either revising your manuscript or making a clear and convincing argument as to why no revision is needed. To facilitate our review, we prefer that the cover letter include the comments made by the reviewers and the editor followed by your response. The revised manuscript should indicate the position of all changes made. We suggest that you use the "track changes" feature in your word processing software to do so (rather than strikethrough or underline formatting). Your paper will be maintained in active status for 21 days from the date of this letter. If we have not heard from you by Jan 25, 2019, we will assume you wish to withdraw the manuscript from further consideration. REVIEWER COMMENTS: Reviewer #1: This manuscript has a purpose to "evaluate the impact of insufficient or excessive gestational weight gain in the first and second trimester on adverse perinatal outcomes, and whether weight gain in the third trimester modifies these risks." This was a retrospective, cohort study using an institutional database, which the authors validated by randomly selecting 300 subjects and manually confirming data in the database. 1. Could the authors please include a 'Precis' for their manuscript? 2. The authors describe BMI and suggested gestational weight gain for the different categories for overweight and obese. Could the authors construct a table with the WHO definition of all the various BMI categories (underweight, normal, overweight, obese) in one column and suggested weight gain for each category in an adjacent column and reference in text? 3. How was gestational age determined? How accurate was determination of gestational age? Was gestational age at birth determined by the Pediatricians with a Ballard score? 4. The authors note that they performed a validation survey by manually abstracting a randomly selected group of 300 charts. How was randomization performed? Why did they select a n=300 charts to validate their database? Reviewer #2: Slight revision-please change "fetal gender" to "fetal sex" in line 145 [gender is a social construct, sex is a biologic construct]. Reviewer #3: This is a retrospective cohort study of over 5000 obese women that examined their weight gain as of 24-28 weeks and relationship to adverse pregnancy outcomes. The manuscript is well written. Line 72: IOM is now the National Academy of Medicine Line 77: "weight gain 11 pounds" I think is missing 'less than' as in weight gain less than 11 pounds