Objective: To describe the outcome of fertility preservation (FP) using vitrified oocytes in patients with endometriosis and to determine the impact of ovarian surgery. Design: Retrospective observational study. Setting: University-affiliated private in vitro fertilization (IVF) center. Patient(s): Four hundred and eighty-five women with endometriosis who underwent FP from January 2007 to July 2018. Intervention(s): Vitrification of metaphase II (MII) oocytes for future use. Main Outcome Measure(s): Oocyte survival rate and cumulative live-birth rate (CLBR). Result(s): Mean age at vitrification was 35.7 AE 3.7 years. The women undergoing operations were younger than the nonsurgical patients (33.4 AE 3.6 years vs. 36.7 AE 3.7 years). The survival rate and CLBR were 83.2% and 46.4%, respectively. The number of vitrified oocytes per cycle (6.2 AE 5.8) was higher for the nonsurgical patients compared with the unilateral (5.0 AE 4.5) or bilateral (4.5 AE 4.4) surgery groups, but was comparable among the surgical patients. The effect of age (adjusted odds ratio [OR] 0.904; 95% CI, 0.858-0.952), number of oocytes (adjusted OR 1.050; 95% CI, 1.025-1.091), and survival (adjusted OR 1.011; 95% CI, 1.001-1.020) on the CLBR was confirmed. However, the effect of surgery was not observed (adjusted OR 1.142; 95% CI, 0.778-1.677). Nonetheless, the ovarian response (vitrified oocytes ¼ 8.6 AE 6.9 vs. 5.1 AE 4.8) and CLBR (72.5% vs. 52.8%) were higher in young (%35 years) nonsurgical patient versus the surgical patients; older women showed similar outcomes. Conclusion(s):Fertility preservation gives patients with endometriosis a valid treatment option to help them increase their reproductive chances. We suggest performing surgery after ovarian stimulation for FP in young women. In older women, an individualized treatment should be considered. (Fertil Steril Ò 2020;113:836-44. Ó2019 by American Society for Reproductive Medicine.) El resumen está disponible en Español al final del artículo.

STUDY QUESTION Is there a serum progesterone (P) threshold on the day of embryo transfer (ET) in artificial endometrium preparation cycles below which the chances of ongoing pregnancy are reduced? SUMMARY ANSWER Serum P levels <8.8 ng/ml on the day of ET lower ongoing pregnancy rate (OPR) in both own or donated oocyte cycles. WHAT IS KNOWN ALREADY We previously found that serum P levels <9.2 ng/ml on the day of ET significantly decrease OPR in a sample of 211 oocyte donation recipients. Here, we assessed whether these results are applicable to all infertile patients under an artificial endometrial preparation cycle, regardless of the oocyte origin. STUDY DESIGN, SIZE, DURATION This prospective cohort study was performed between September 2017 and November 2018 and enrolled 1205 patients scheduled for ET after an artificial endometrial preparation cycle with estradiol valerate and micronized vaginal P (MVP, 400 mg twice daily). PARTICIPANTS/MATERIALS, SETTING, METHODS Patients ≤50 years old with a triple-layer endometrium ≥6.5 mm underwent transfer of one or two blastocysts. A total of 1150 patients treated with own oocytes without preimplantation genetic testing for aneuploidies (PGT-A) (n = 184), own oocytes with PGT-A (n = 308) or donated oocytes (n = 658) were analyzed. The primary endpoint was the OPR beyond pregnancy week 12 based on serum P levels measured immediately before ET. MAIN RESULTS AND THE ROLE OF CHANCE Women with serum P levels <8.8 ng/ml (30th percentile) had a significantly lower OPR (36.6% vs 54.4%) and live birth rate (35.5% vs 52.0%) than the rest of the patients. Multivariate logistic regression showed that serum P < 8.8 ng/ml was an independent factor influencing OPR in the overall population and in the three treatment groups. A significant negative correlation was observed between serum P levels and BMI, weight and time between the last P dose and blood tests and a positive correlation was found with age, height and number of days on HRT. Multivariate logistic regression showed that only body weight was an independent factor for presenting serum P levels <8.8 ng/ml. Obstetrical and perinatal outcomes did not differ in patients with ongoing pregnancy regardless of serum P levels being above/below 8.8 ng/ml. LIMITATIONS, REASONS FOR CAUTION Only women with MVP were included. Extrapolation to other P administration forms needs to be validated. WIDER IMPLICATIONS OF THE FINDINGS This study identified the threshold of serum P as 8.8 ng/ml on the day of ET for artificial endometrial preparation cycles necessary to optimize outcomes, in cycles with own or donated oocytes. One-third of patients receiving MVP show inadequate levels of serum P that, in turn, impact the success of the ART cycle. Monitoring P levels in the mid-luteal phase is recommended when using MVP to adjust the doses according to the needs of the patient. STUDY FUNDING/COMPETING INTEREST(S) None. TRIAL REGISTRATION NUMBER NCT03272412.

for confounders, logistic and Poisson regression models, adjusted a priori for oocyte age, donor egg, and serum P measurement on day 3, were used to estimate the odds ratio (OR) or relative risk (RR) and 95% confidence interval (CI) of live birth.RESULTS: Mean serum P at transfer on day 5 was 28.4AE10.5 ng/mL. Compared to patients with P>20 ng/mL, patients with P<20 ng/mL on day 3 or 5 had a significantly higher implantation failure rate (negative hCG, 30.8% vs 22.3%, OR 1.54, 95% CI 1.07-2.22), lower CPR (57.9% vs 67.8%, OR 0.66, 95% CI 0.47-0.91) and lower LBR (45.1 vs 58.1%, OR 0.60, 95% CI 0.43-0.83), even after increasing P dose (Table ). LBRs were stable from serum P 20 to 60 ng/mL (assay upper limit); there was no upper limit of P above which the LBR declined. Among obese patients (BMI>30 kg/m2, n¼129), P<20 ng/mL was more common than in non-obese patients (n¼672) (52.7% vs 18.9%, OR 4.76, 95% CI 3.2-7.1). Among patients with P>20 ng/mL, the LBR was significantly lower in obese vs. non-obese patients (44.6 vs 57.7%, OR 0.60, 95% CI 0.38-0.96).CONCLUSIONS: Serum P>20 ng/mL was associated with increased CPR and LBR following blastocyst transfer into a prepared uterus. LBRs were not rescued by increasing P doses for serum levels <20 ng/mL. Obese recipients may require higher initial doses of IM P for luteal support. Future research is needed to define the optimal serum P at transfer, and to determine whether this varies according to patient characteristics, such as BMI.

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Study question Is there an optimal serum progesterone (P) threshold in frozen embryo transfer (FET) modified natural cycles when luteal phase support (LPS) is given? Summary answer Serum P measured on the day of ET is not related with ongoing pregnancy outcome when doing a modified natural cycle with LPS. What is known already Recent publications showed that there is a minimum threshold of serum P that needs to be reached in artificial cycles to optimize pregnancy rates. When using micronized vaginal P (MVP), about 30% of patients show low levels of serum P (&lt;9 ng/mL) leading to a significant decrease in ongoing pregnancy; although this situation can be reverted by increasing and modifying the route of exogenous P. In pure natural cycles without LPS, serum P below 10 ng/mL impairs pregnancy outcome. Nevertheless, there is no data about the impact of serum P levels in modified natural cycles in which LPS is given. Study design, size, duration Prospective cohort unicentric study performed in IVI RMA Valencia (Spain), including 244 cycles from February 2020 to January 2021. Participants/materials, setting, methods Infertile patients &lt;50 y.o. and BMI&lt;40Kg/m2 undergoing a FET of a maximum of 2 blastocysts, from own or donated oocytes. FET were performed in the context of a modified natural cycle (single injection of rec-hCG when dominant follicle reached 17mm and endometrial thickness &gt;6.5mm). MVP was used for LPS (200mg/12h). Ongoing pregnancy rate (OPR) was correlated with serum P levels on the FET day, measured within two hours before transfer. Main results and the role of chance A total of 241 patients were analyzed. Mean age was 38.1 + 3.8 years, with a mean BMI of 23.3 + 3.9. On the rec-hCG day the mean leading follicle size was 17.7±0.1 mm. The endometrium displayed a trilaminar pattern, with a mean thickness of 7.8±3.3 mm, and mean P and estradiol (E2) levels were 0.30±0.03 ng/ml and 249.39±11.03  pg/ml, respectively. A mean of 1.1 blastocysts were transferred (90.9% were single embryo transfers), 27.4% (66) from donated and 72.6 % (175) from own oocytes. On the day of FET, the mean serum P and E2 levels were 26.19 + 8.97ng/mL and 154.12 + 96.08pg/mL, respectively. The overall OPR was 51.5% (124). OPR according to quartiles of serum P (ng/mL) was 56.7% (Q1, P &lt; 20.2), 47.5% (Q2, P &gt; 20.2-24.8), 51.7% (Q3, P &gt; 24.8-31.1), 50.0% (Q4, P &gt; 31.1), p = 0.78). Multivariate logistic regression showed that serum P was not related with OPR after adjusting for age, BMI, E2 and origin of oocytes (aOR:0.98, 95% CI:0.93-1.04, p = 0.47). Only 2 patients had serum P levels below 10 ng/mL, with values of 8.6 and 8.8 ng/mL on the ET day and had a negative pregnancy test. Limitations, reasons for caution As part of our routine clinical practice, MVP (200mg/12h) is given for LPS in patients undergoing a FET in the context of a modified natural cycle. Thus, these results cannot be extrapolated to LPS-free or any other LPS protocol in FET modified natural cycles. Wider implications of the findings The majority of patients undergoing FET in modified natural cycles when using LPS have adequate levels of serum P and thus, do not have an impact on pregnancy outcome. According to our data, there is no need to measure serum P levels on the luteal phase of modified natural cycles. Trial registration number NCT04259996