Presence of Adenomyosis Impairs Clinical Outcomes in Women Undergoing Frozen Embryo Transfer: A Retrospective Cohort Study.

(1) Background: The presence of adenomyosis among pregnant patients has been associated with a higher incidence of miscarriage and pregnancy complications. Although the role of adenomyosis in women undergoing in vitro fertilization (IVF) was investigated in several studies and demonstrated a potentially detrimental effect on live birth rates following IVF, most of them were small studies in which the adenomyosis diagnosis was not confirmed based on solid ultrasonographic criteria. (2) Methods: 3503 patients undergoing their first blastocyst frozen transfer through a hormonal replacement (HRT) FET cycle. Among them, 140 women had a confirmed diagnosis of adenomyosis based on the MUSA criteria. (3) Results: Adenomyosis patients were more likely to proceed with deferred FET compared with no-adenomyosis women (p = 0.002) and were significantly more likely to be treated with GnRH agonist pre-treatment (2 months) (p < 0.001). The presence of adenomyosis significantly decreased the clinical pregnancy rates (aOR 0.62, 95% CI: 0.39-0.98, p = 0.040) and live birth rates (aOR 0.46, 95% CI: 0.27-0.75, p = 0.003) and significantly increased the miscarriage rates (aOR 2.13, 95% CI: 0.98-4.37, p = 0.045). Multivariable logistic regression adjusting for age, autologous or donor oocytes, PGT-A, deferred FET, serum progesterone levels the day before FET, GnRH agonist pre-treatment, number of embryos transferred, and adenomyosis demonstrated that the use of the GnRH agonist protocol did not decrease or increase the miscarriage rate, clinical pregnancy rate, or live birth rate. (4) Conclusions: The presence of adenomyosis had a significant negative impact on the clinical outcomes of patients undergoing FET and was associated with higher miscarriage, lower clinical pregnancy, and live birth rates. GnRH agonist pre-treatment does not appear to improve clinical outcomes.

Elevated serum progesterone levels before frozen embryo transfer do not negatively impact reproductive outcomes: a large retrospective cohort study.

OBJECTIVE: To evaluate whether patients with high-serum progesterone levels before frozen embryo transfer (FET) under hormonal replacement therapy present with worse reproductive outcomes. DESIGN: A cohort retrospective study. SETTING: A university-affiliated fertility center. PATIENT(S): A total of 3,183 FET cycles in patients receiving hormonal replacement therapy between March 2009 and December 2020 were included. The luteal phase was covered with 200 mg per 8 hours of vaginal micronized progesterone either alone or in combination with a daily subcutaneous injection of 25 mg of progesterone. A total of 1,360 cycles corresponded to frozen homologous embryo transfer (ET) (hom-FET), 1,024 were euploid ET (eu-FET) after preimplantation genetic testing for aneuploidies, and 799 cycles were frozen heterologous ET (het-FET). All patients had adequate serum progesterone levels (≥10.6 ng/mL) before the procedure. INTERVENTION(S): Frozen embryo transfer cycles. MAIN OUTCOME MEASURE(S): Clinical pregnancy, miscarriage, and live birth rates (LBRs). RESULTS: Median (P25; P75) serum progesterone level before FET was 14.39 (12.43-17.49) ng/mL. Progesterone levels were significantly higher in the group under vaginal plus subcutaneous progesterone (15.96 [13.74-21.60] vs. 14.09 [12.19-16.95]). No differences in clinical pregnancy, miscarriage, and LBR were observed based on the use of vaginal or vaginal plus subcutaneous progesterone for each of the groups (hom-FET, eu-FET, and het-FET). Live birth rates were comparable among patients in the highest centile of serum progesterone levels (≥p90) (22.33 ng/mL) and the rest of the patients (p<90) (43.9% vs. 41.3%). Patients with progesterone levels ≥p90 presented lower body mass index than those in the lower centiles (

The effect of trophectoderm biopsy technique and sample handling on artefactual mosaicism.

PURPOSE: To determine whether embryo mosaicism prevalence in preimplantation genetic testing for aneuploidy (PGT-A) cycles is associated with the trophectoderm biopsy technique used (a. number of laser pulses or b. the use of flicking or pulling) or the time to tubing. METHODS: Prospective observational study performed in a single IVF-PGT-A setting from May 2019 to May 2021. Trophectoderm biopsies were analysed by next-generation sequencing. Mosaicism was analysed in relation to the biopsy methodology (number of laser pulses and pulling vs flicking), time elapsed from biopsy to tubing (min), and time of sample cryostorage from tubing to amplification (days). As a secondary objective, the number of laser pulses and biopsy methodology were studied in relation to clinical outcomes of transferred euploid blastocysts. RESULTS: None of the analysed variables were associated to mosaicism prevalence. Multivariable regression analysis demonstrated that mosaicism prevalence was comparable either when  > 3 laser pulses were used as compared to ≤ 3 (13.9% vs 13.8%, aOR = 0.8726 [0.60-1.28]) and pulling compared to flicking (13.1% vs 14.0%, aOR = 0.86 [0.60-1.23]). Moreover, neither the number of laser pulses during biopsy (> 3 vs ≤ 3) nor the technique used (pulling vs flicking) were associated with clinical pregnancy after the transfer of frozen-thawed euploid blastocysts (54.9% vs 55.2%, aOR = 1.05 [0.53-2.09]; 61.1% vs 52.9%, aOR = 1.11 [0.55-2.25], respectively). CONCLUSION: Our results suggest that, as long as the biopsy and tubing procedures are performed following standardized high quality procedures, no specific approach would increase the generation of artefactual mosaicism as a result of trophectoderm biopsy. Trophectoderm biopsies should be performed regardless of the methodology but always aiming on minimising blastocyst manipulation.

Individualised luteal phase support in artificially prepared frozen embryo transfer cycles based on serum progesterone levels: a prospective cohort study.

STUDY QUESTION: Does an individualised luteal phase support (iLPS), according to serum progesterone (P4) level the day prior to euploid frozen embryo transfer (FET), improve pregnancy outcomes when started on the day previous to embryo transfer? SUMMARY ANSWER: Patients with low serum P4 the day prior to euploid FET can benefit from the addition of daily subcutaneous P4 injections (Psc), when started the day prior to FET, and achieve similar reproductive outcomes compared to those with initial adequate P4 levels. WHAT IS KNOWN ALREADY: The ratio between FET/IVF has spectacularly increased in the last years mainly thanks to the pursuit of an ovarian hyperstimulation syndrome free clinic and the development of preimplantation genetic testing (PGT). There is currently a big concern regarding the endometrial preparation for FET, especially in relation to serum P4 levels around the time of embryo transfer. Several studies have described impaired pregnancy outcomes in those patients with low P4 levels around the time of FET, considering 10 ng/ml as one of the most accepted reference values. To date, no prospective study has been designed to compare the reproductive outcomes between patients with adequate P4 the day previous to euploid FET and those with low, but restored P4 levels on the transfer day after iLPS through daily Psc started on the day previous to FET. STUDY DESIGN, SIZE, DURATION: A prospective observational study was conducted at a university-affiliated fertility centre between November 2018 and January 2020 in patients undergoing PGT for aneuploidies (PGT-A) IVF cycles and a subsequent FET under hormone replacement treatment (HRT). A total of 574 cycles (453 patients) were analysed: 348 cycles (leading to 342 euploid FET) with adequate P4 on the day previous to FET, and 226 cycles (leading to 220 euploid FET) under iLPS after low P4 on the previous day to FET, but restored P4 levels on the transfer day. PARTICIPANTS/MATERIALS, SETTING, METHODS: Overall we included 574 HRT FET cycles (453 patients). Standard HRT was used for endometrial preparation. P4 levels were measured the day previous to euploid FET. P4 > 10.6 ng/ml was considered as adequate and euploid FET was performed on the following day (FET Group 1). P4 < 10.6 ng/ml was considered as low, iLPS was added in the form of daily Psc injections, and a new P4 analysis was performed on the following day. FET was only performed on the same day when a restored P4 > 10.6 ng/ml was achieved (98.2% of cases) (FET Group 2). MAIN RESULTS AND THE ROLE OF CHANCE: Patient's demographics and cycle parameters were comparable between both euploid FET groups (FET Group 1 and FET Group 2) in terms of age, weight, oestradiol and P4 levels and number of embryos transferred. No statistically significant differences were found in terms of clinical pregnancy rate (56.4% vs 59.1%: rate difference (RD) -2.7%, 95% CI [-11.4; 6.0]), ongoing pregnancy rate (49.4% vs 53.6%: RD -4.2%, 95% CI [-13.1; 4.7]) or live birth rate (49.1% vs 52.3%: RD -3.2%, 95% CI [-12; 5.7]). No significant differences were also found according to miscarriage rate (12.4% vs 9.2%: RD 3.2%, 95% CI [-4.3; 10.7]). LIMITATIONS, REASONS FOR CAUTION: Only iLPS through daily Psc was evaluated. The time for Psc injection was not stated and no serum P4 determinations were performed once the pregnancy was achieved. WIDER IMPLICATIONS OF THE FINDINGS: Our study provides information regarding an 'opportunity window' for improved ongoing pregnancy rates and miscarriage rates through a daily Psc injection in cases of inadequate P4 levels the day previous to FET (P4 < 10.6 ng/ml) and restored values the day of FET (P4 > 10.6 ng/ml). Only euploid FET under HRT were considered, avoiding one of the main reasons of miscarriage and implantation failure and overcoming confounding factors such as female age, embryo quality or ovarian stimulation protocols. STUDY FUNDING/COMPETING INTEREST(S): No external funding was received. B.C. reports personal fees from MSD, Merck Serono, Ferring Pharmaceuticals, IBSA and Gedeon Richter outside the submitted work. N.P. reports grants and personal fees from MSD, Merck Serono, Ferring Pharmaceuticals, Theramex and Besins International and personal fees from IBSA and Gedeon Richter outside the submitted work. The remaining authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: NCT03740568.

Prevalence, types and possible factors influencing mosaicism in IVF blastocysts: results from a single setting.

RESEARCH QUESTION: Are intrinsic or extrinsic factors associated with embryo mosaicism prevalence in IVF cycles? DESIGN: Retrospective cohort study of preimplantation genetic testing for aneuploidy (PGT-A) cycles carried out at a university-affiliated IVF clinic between October 2017 and October 2019. Trophectoderm biopsies were analysed by next generation sequencing. Mosaicism prevalence, type of anomaly and the chromosomes involved were analysed. Intrinsic and extrinsic factors potentially inducing mosaicism were studied: maternal and paternal age, antral follicle count, cumulus-oocyte complexes retrieved, female body mass index, PGT-A indication, sperm concentration, total dosage of gonadotrophins, embryo quality and day of blastocyst formation, single-step commercial media used and biopsy operator. RESULTS: Overall prevalence of mosaicism in our PGT-A setting was 13.9%. In segmental mosaicism, larger chromosomes tended to be more affected, which was not observed in whole-chromosome mosaicism. Additionally, segmental mosaicism was mostly observed in monosomy (69.6%; P < 0.01) compared with whole-chromosome mosaicism (49.7% monosomies versus 50.3% trisomies; P = 0.83). Although a high inter-patient variability was observed, only paternal age showed a positive association with mosaicism (adjusted OR 1.26, 95% CI 1.02 to 1.54) among the analysed variables. CONCLUSIONS: Our results suggest remarkable differences in the mechanisms generating segmental and whole-chromosome mosaicism, indicating that they may deserve different consideration when studying them and when prioritizing them for transfer. Male factor seems to be associated with mosaicism and may be worthy of specific assessment in future studies.

COH outcomes in breast cancer patients for fertility preservation: a comparison with the expected response by age.

PURPOSE: Breast cancer is the most common cancer diagnosed during childbearing age, and fertility preservation is becoming increasingly more essential. However, recent studies indicate a possible poorer response to controlled ovarian hyperstimulation (COH) in cancer patients than in non-cancer controls and a negative impact of BRCA mutations on female fertility. This study aims to evaluate ovarian response and the number of mature oocytes (MII) vitrified in women with breast cancer, with or without BRCA mutation, comparing them to the expected response according to an age-related nomogram. METHODS: This is a retrospective observational study involving sixty-one breast cancer patients who underwent COH for oocyte cryopreservation. The age-specific nomogram was built using 3871 patients who underwent COH due to oocyte donation, fertility preservation for non-medical reasons, or FIVET for male factor exclusively. RESULTS: The mean number of oocytes retrieved was 13.03, whereas the mean number of MII oocytes was 10.00. After the application of the z-score, no statistically significant differences were found compared with the expected response in the general population, neither by dividing patients according to the presence or absence of BRCA mutation nor according to the phase in which they initiated stimulation. CONCLUSION: The results obtained do not support the notion of a negative impact of the BRCA mutation on the ovarian response of women with breast cancer. Women with breast cancer undergoing COH for fertility preservation can expect the ovarian response predicted for their age.

Low progesterone levels on the day before natural cycle frozen embryo transfer are negatively associated with live birth rates.

STUDY QUESTION: Are progesterone (P) levels on the day before natural cycle frozen embryo transfer (NC-FET) associated with live birth rate (LBR)? SUMMARY ANSWER: Regular ovulatory women undergoing NC-FET with serum P levels <10 ng/ml on the day before blastocyst transfer have a significantly lower LBR than those with serum P levels >10 ng/ml. WHAT IS KNOWN ALREADY: The importance of serum P levels around the time of embryo transfer in patients undergoing FET under artificial endometrial preparation has been well established. However, no study has analyzed the importance of serum P levels in patients undergoing FET under a true natural endometrial preparation cycle. STUDY DESIGN, SIZE, DURATION: This was a retrospective cohort study including 294 frozen blastocyst transfers under natural cycle endometrial preparation at a university-affiliated fertility centre between January 2016 and January 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients had regular menstrual cycles and underwent NC-FET with their own oocytes. Only patients who had undergone serum P measurement between 8 am and 11 am on the day before FET were included. Patients did not receive any external medication for endometrial preparation or luteal phase support. Patients were divided into two groups according to serum P levels below or above 10 ng/ml on the day before FET. Univariate analysis was carried out to describe and compare the cycle characteristics with reproductive outcomes. To evaluate the effect of P, a multivariable logistic model was fitted for each outcome after adjusting for confounding variables. MAIN RESULTS AND THE ROLE OF CHANCE: Mean serum P levels on the day before FET were significantly higher in patients who had a live birth compared to those who did not (14.5 ± 7.0 vs 12.0 ± 6.6 ng/ml, 95% CI [0.83; 4.12]). The overall clinical pregnancy rate (CPR) and LBR were 42.9% and 35.4%, respectively. Patients in the higher P group (>10 ng/ml) had a higher LBR (41.1% vs 25.7%: risk difference (RD) 15.4%, 95% CI [5; 26]) and CPR (48.6% vs 33.0%: RD 15.6%, 95% CI [4; 27]). Patients with higher serum P levels on the day before FET (63% of patients) had an improved LBR (odds ratio: 1.05; 95% CI [1.02; 1.09]). Women with serum P levels <10 ng/ml on the day before FET (37% of patients) had significantly higher weights (62.5 ± 9.9 vs 58.1 ± 7.1 kg, 95% CI [1.92; 6.90]) and BMI (22.9 ± 3.6 vs 21.6 ± 2.7 kg/m2, 95% CI [0.42; 2.25]) compared to patients with P levels >10 ng/ml. LIMITATIONS, REASONS FOR CAUTION: The main limitation of our study is its retrospective design. Other potential limitations are the detection of LH surge through urine testing and the inclusion of patients who did and did not undergo preimplantation genetic testing for aneuploidies. The protocol used in our institution for monitoring NC-FET does not look for the onset of progesterone secretion by the corpus luteum, and a slow luteinisation process or delay of corpus luteum function cannot be ruled out. WIDER IMPLICATIONS OF THE FINDINGS: We provide evidence that a minimum serum P threshold (P >10 ng/ml) might be required for improved reproductive outcomes in NC-FET. This result suggests that there are different mechanisms by which P is produced and/or distributed by each patient. This study also provides an excellent model to evaluate the impact of luteal phase defect through NC-FET. A prospective evaluation to assess whether P supplementation should be individualised according to patient's needs is necessary to support our findings. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used, and there are no competing interests.

Factors associated with serum progesterone concentrations the day before cryopreserved embryo transfer in artificial cycles.

RESEARCH QUESTION: What factors determine serum progesterone concentrations the day before cryopreserved embryo transfer in artificially prepared cycles? DESIGN: Retrospective cohort study at a university-affiliated fertility centre including infertile women under 45 years old using own oocytes who underwent a total of 685 single cryopreserved blastocyst transfers under hormonal therapy. Determinants that affected live birth rate (LBR) were analysed using a multivariate logistic regression. Univariate analysis and multivariate linear regression were used to evaluate independent factors that affect serum progesterone concentrations. RESULTS: Age (odds ratio [OR] 0.93; 95% confidence interval [CI] 0.89-0.96), duration of oestradiol (OR 0.96; 95% CI 0.92-0.99), serum progesterone concentrations (OR 1.04; 95% CI 1.01-1.08) and patients who underwent preimplantation genetic testing for aneuploidies (PGT-A) (OR 2.17; 95% CI 1.55-3.03) were independently associated with LBR. After univariate analysis, determinants of progesterone concentrations were: age, weight, history of a previous cryopreserved embryo transfer with serum progesterone concentrations <10 ng/ml, and time of blood extraction. The multivariate linear regression showed that increasing age presented a positive correlation with progesterone concentrations (ß = 0.11; 95% CI 0.01-0.20). On the contrary, significant negative correlations with progesterone concentrations were shown for a previous history of serum progesterone value <10 ng/ml (ß = -3.13; 95% CI -4.45 to -1.81]), higher weight (ß = -0.05; 95% CI -0.08 to -0.01) and the time of blood sampling during the day (ß = -0.13; 95% CI -0.25 to -0.01). CONCLUSIONS: This study adds more evidence regarding the importance of serum progesterone concentrations before frozen embryo transfer (FET). It also showed that body weight, age, time of blood sampling and a history of low progesterone are determinants associated with progesterone concentrations before blastocyst FET.

Does LH suppression by progesterone-primed ovarian stimulation compared with GnRH antagonist affect live birth rate among oocyte recipients?

RESEARCH QUESTION: Is live birth rate among recipients of donated oocytes different depending on mode of treatment for endogenous LH suppression administered to oocyte donors during ovarian stimulation? DESIGN: A retrospective cohort study of recipients of freshly donated oocytes from oocyte donors who underwent ovarian stimulation with gonadotrophins at a private, university-based infertility clinic between January 2017 and March 2018. For endogenous LH suppression, oocyte donors received daily injections of gonadotrophin releasing hormone antagonist ganirelix (GNR) or daily oral 75 µg desogestrel (DSG) until triggering with 0.2 mg of triptorelin. Three hundred recipient cycles of freshly donated oocytes were included: 154 from oocyte donor DSG cycles and 146 from oocyte donor GNR cycles. RESULTS: Comparison of basal characteristics of oocyte donors showed no differences in mean age, anti-Müllerian hormone levels and body mass index between the oocyte donor DSG p and oocyte donor GNR groups, respectively. Similarly, no differences were observed among mean age of recipients and body mass index. Out of 300 fresh embryo transfers, 190 clinical pregnancies (63.3%) and 150 live births (50%) were achieved. Per embryo transfer clinical pregnancy rate was 66.2% in the DSG recipient group and 60.3% in the GNR recipient group (P = 0.338). Live birth rates were not significantly different between both groups (48.7% among DSG recipient group and 51.4% among GNR recipient group; P = 0.729). CONCLUSIONS: Live birth rate among recipients of donated oocytes does not differ depending on the mode of treatment for endogenous LH suppression administered to the oocyte donors during ovarian stimulation. This information is reassuring and will be of interest to teams using these kinds of protocols, although further research is needed.

Impaired Expression of Ectonucleotidases in Ectopic and Eutopic Endometrial Tissue Is in Favor of ATP Accumulation in the Tissue Microenvironment in Endometriosis.

Endometriosis is a prevalent disease defined by the presence of endometrial tissue outside the uterus. Adenosine triphosphate (ATP), as a proinflammatory molecule, promotes and helps maintain the inflammatory state of endometriosis. Moreover, ATP has a direct influence on the two main symptoms of endometriosis: infertility and pain. Purinergic signaling, the group of biological responses to extracellular nucleotides such as ATP and nucleosides such as adenosine, is involved in the biology of reproduction and is impaired in pathologies with an inflammatory component such as endometriosis. We have previously demonstrated that ectonucleotidases, the enzymes regulating extracellular ATP levels, are active in non-pathological endometria, with hormone-dependent changes in expression throughout the cycle. In the present study we have focused on the expression of ectonucleotidases by means of immunohistochemistry and in situ activity in eutopic and ectopic endometrial tissue of women with endometriosis, and we compared the results with endometria of women without the disease. We have demonstrated that the axis CD39-CD73 is altered in endometriosis, with loss of CD39 and CD73 expression in deep infiltrating endometriosis, the most severe, and most recurring, endometriosis subtype. Our results indicate that this altered expression of ectonucleotidases in endometriosis boosts ATP accumulation in the tissue microenvironment. An important finding is the identification of the nucleotide pyrophophatase/phosphodiesterase 3 (NPP3) as a new histopathological marker of the disease since we have demonstrated its expression in the stroma only in endometriosis, in both eutopic and ectopic tissue. Therefore, targeting the proteins directly involved in ATP breakdown could be an appropriate approach to consider in the treatment of endometriosis.

What is the clinical impact of the endometrial receptivity array in PGT-A and oocyte donation cycles?

PURPOSE: To evaluate the influence of the endometrial receptivity array (ERA) test on the implantation rate (IR) and pregnancy rate (PR) in patients with previous failed euploid embryo transfers (Euploid-ET) or oocyte donation embryo transfers (Donor-ET). METHODS: Single-center retrospective study of patients with ≥ 1 previous failed Euploi-ET (n = 24) or ≥ 2 failed Donor-ET (n = 32) who underwent an ERA test and a post-ERA Euploid-ET/Donor-ET between 2012 and 2018. Controls were patients with ≥ 1 previously failed Euploid-ET (n = 119) or ≥ 2 failed Donor-ET (n = 158) who underwent Euploid-ET/Donor-ET during the same period without performing an ERA test. Only blastocyst stage embryos were included. IR/PR was compared between the post-ERA ET and the last ET in the control group. RESULTS: There was no statistically significant difference regarding IR [55.6% (34.6-76.5%) vs. 65.0% (56.9-73.1%)] nor PR (58.3% vs.70.6%, p = 0.238) in the Euploid-ET ERA vs. Euploid-ET control groups. In the Donor-ET arm, both IR [26.8% (12.3-41.4%) vs. 57.2% (50.1-64.3%)] and PR (34.4% vs. 65.2%, p = 0.001) were significantly lower in the ERA group. Multivariate analysis confirmed that performing an ERA test did not influence the PR in the Euploid-ET arm and was associated with a diminished PR in the Donor-ET arm. In the ERA group, 41.1% patients were non-receptive (NR). No significant difference was found regarding IR/PR in NR vs. receptive patients in both Euploid-ET/Donor-ET arms. CONCLUSIONS: In our sample, the performance of an ERA test did not improve pregnancy outcomes. Future prospective studies in larger samples are needed to confirm the role of the ERA test in Euploid-ET/Donor-ET.

Desogestrel versus antagonist injections for LH suppression in oocyte donation cycles: a crossover study.

To study whether ovarian response to corifollitropin among oocyte donors (OD) is different when oral desogestrel (DSG) is used to block the luteinizing hormone (LH) surge when compared to GnRH-antagonist use. This is a retrospective, cohort study at a private, university-based, IVF center including 35 OD. Patients underwent two stimulation cycles under corifollitropin alfa (CFT), one under an antagonist and another under DSG, between February 2015 and May 2017. In antagonist cycles, daily ganirelix was administered since a leading follicle reached 14 mm. In the DSG cycles, daily oral DSG was prescribed. The main outcome measure was oocytes retrieved. Compared to antagonist cycles, cycles under DSG received fewer injections (10.3 ± 2.8 vs. 5.0 ± 2.1, p < .001), nominally lower total supplementary gonadotropin dose (497.4 ± 338.9I U vs. 442.9 ± 332.8 IU, p=.45) with a lower total cost of medication (1018.6 ± 191.0€ vs. 813.8 ± 145.9€, p<.001). There were no differences in the total number of retrieved oocytes between groups (17.4 ± 7.5 vs. 18.6 ± 8.9, p=.34). In the corresponding oocyte recipients, clinical pregnancy rate was similar between groups: 52.0% vs. 58.6%, respectively (p=.78). ODs' stimulation's response under DSG is similar when compared to (17.4 ± 7.5 vs. 18.6 ± 8.9, p=.34) but associated with less injections and lower medication costs. The main advantage of this strategy is its simplicity, an aspect of utmost importance in the management of ODs.

Ovarian response in oocyte donation cycles under LH suppression with GnRH antagonist or desogestrel progestin: retrospective and comparative study.

Here are investigated the serum hormones in ovarian stimulation cycles of oocyte donors (OD), under endogenous luteinizing hormone (LH) suppression with GnRH antagonist (antGnRH) vs. desogestrel (DSG) (progesterone-primed [PP]). OD underwent ovarian stimulation with gonadotropins at a private, university-based, infertility center between January 2017 and March 2018. Endogenous LH peak was controlled with either daily injections of antGnRH or with daily oral 75 mcg DSG (PP) until triggering. LH and progesterone were measured at trigger and the following day. A total of 404 OD cycles were included. There were no differences in age (26.7 ± 4.9 vs. 27.1 ± 4.8 years), AMH (3.7 ± 2.1 vs. 4.1 ± 2.7 ng/ml), and body mass index (BMI) (22.4 ± 2.8 vs. 22.1 ± 3.0 kg/m2) between PP and antGnRH groups, respectively. On the day of trigger, progesterone was lower in PP compared to antGnRH (0.9 ± 0.7, vs. 1.5 ± 1.2 ng/ml, p < .001), whereas no significant differences existed in estradiol or LH. On the day after trigger, lower progesterone in PP vs. antGnRH (10.8 ± 6.0 vs. 13.4 ± 7.9 ng/ml, p=.002) was observed. No differences were observed in the number of retrieved oocytes or the clinical pregnancies among recipients. Our study shows that endocrine response to DSG differs significantly as compared to antGnRH use for the control of endogenous LH without apparent impact on number of retrieved oocytes or the clinical pregnancies among recipients.

The ectonucleoside triphosphate diphosphohydrolase-2 (NTPDase2) in human endometrium: a novel marker of basal stroma and mesenchymal stem cells.

The human endometrium undergoes repetitive regeneration cycles in order to recover the functional layer, shed during menses. The basal layer, which remains in charge of endometrial regeneration in every cycle, contains adult stem or progenitor cells of epithelial and mesenchymal lineage. Some pathologies such as adenomyosis, in which endometrial tissue develops within the myometrium, originate from this layer. It is well known that the balance between adenosine triphosphate (ATP) and adenosine plays a crucial role in stem/progenitor cell physiology, influencing proliferation, differentiation, and migration. The extracellular levels of nucleotides and nucleosides are regulated by the ectonucleotidases, such as the nucleoside triphosphate diphosphohydrolase 2 (NTPDase2). NTPDase2 is a membrane-expressed enzyme found in cells of mesenchymal origin such as perivascular cells of different tissues and the stem cells of adult neurogenic regions. The aim of this study was to characterize the expression of NTPDase2 in human nonpathological cyclic and postmenopausic endometria and in adenomyosis. We examined proliferative, secretory, and atrophic endometria from women without endometrial pathology and also adenomyotic lesions. Importantly, we identified NTPDase2 as the first marker of basal endometrium since other stromal cell markers such as CD10 label the entire stroma. As expected, NTPDase2 was also found in adenomyotic stroma, thus becoming a convenient tracer of these lesions. We did not record any changes in the expression levels or the localization of NTPDase2 along the cycle, thus suggesting that the enzyme is not influenced by the female sex hormones like other previously studied ectoenzymes. Remarkably, NTPDase2 was expressed by the Sushi Domain containing 2 (SUSD2)+ endometrial mesenchymal stem cells (eMSCs) found perivascularly, rendering it useful as a cell marker to improve the isolation of eMSCs needed for regenerative medicine therapies.

Ultrasonographically diagnosed dermoid cysts do not influence ovarian stimulation response in an in vitro fertilization cycle.

To determine if patients with a DC respond similarly to ovarian stimulation when compared to patients without a DC. Infertility patients with a DC that underwent IVF between January 2009 and December 2016 were included. A cystic mass with mixed echogenicity, internal echoes similar to thick bands, fatty-fluid level, or an echogenic tubercle with acoustic shadow (Rokitansky nodule) within two years of the cycle characterized the diagnosis. The z-score compared the standard deviations (SDs) in patients with/without a DC and were compared to a nomogram (expected oocytes minus oocytes obtained divided by the SD), adjusted for age and number of oocytes retrieved, built utilizing cycles from noninfertile female patients. Thirty-nine patients with DC and 7839 patients without DC were identified. The mean number of oocytes (8.6 ± 5.8 vs. 8.5 ± 7.7, p = .43) and MIIs (6.7 ± 4.7 vs. 7.0 ± 6.7, p = .74) retrieved were similar. When cycles with and without a DC were compared to the nomogram (z-score of 0), cycles with a DC presented a z-score for ovarian response of 0.1921 SDs from the mean, and patients without DC presented a z-score of -0.2065 SDs from the mean (similar and less than -1.0). After building a population 'normal' response as a template, patients with and without a DC responded similar to COS.

Inconclusive results in preimplantation genetic testing: go for a second biopsy?

The transition in biopsy timing from blastomere to trophectoderm biopsy has led to a remarkable decrease in the percentage of undiagnosed blastocysts. However, patients with few or no euploid blastocysts can be affected by this residual percentage of diagnosis failure. The aim of this study is to assess whether blastocyst rebiopsy and revitrification is an efficient and safe procedure to be applied in cases of no results after analysis. Fifty-three patients agreed to the warming of 61 blastocysts to perform a second biopsy and PGT-A by aCGH. Only 75.4% of the blastocysts survived, reexpanded, and could be rebiopsied. After the second biopsy and analysis, 95.6% of the blastocysts were successfully diagnosed with an euploidy rate of 65.9%. Eighteen euploid blastocysts were warmed and transferred to 18 patients with a 100% survival and reexpansion rate. Seven clinical pregnancies have been achieved with 4 live births, 1 ongoing pregnancy, and 2 miscarriages. Thus, although few transfers of rebiopsied and revitrified blastocysts have been performed till date, our preliminary results show that this approach is efficient and safe to be applied for undiagnosed blastocysts, as it ultimately allows the transfer of euploid blastocysts and good clinical outcomes.

Linking back-to-back stimulation cycles with oral contraceptives or progestins in women undergoing embryo accumulation for preimplantation genetic testing, a retrospective study.

This retrospective study was carried out to determine which strategy is associated with improved outcomes in two back-to-back cycles when undergoing embryo accumulation. Eighty patients with two stimulation cycles performed with <45 days between retrievals between Jan'16-Mar'17 were included. Patients were segregated according to the strategy used to link stimulations: spontaneous menses (SM), vaginal micronized progesterone (VMP) or oral contraceptive pills (OCP). Main outcome measure was oocytes retrieved. The oocytes retrieved difference between cycles was -0.9 in SM, -1.5 in VMP and +0.4 in OCPs. Although not statistically significant, more oocytes retrieved were observed in the 2ndcycle when OCPs were used (9.0 ± 3.7 vs. 9.4 ± 4.1)? whereas fewer oocytes retrieved were observed when SM (9.4 ± 3.9 vs. 8.5 ± .0) or VMP (9.8 ± 5.7 vs. 8.2 ± 4.4) were used. After adjusting for age, gonadotropins and stimulation days (2nd cycle) and treatment group in an ANCOVA model, no treatment was associated with a higher average number of oocytes retrieved (power: 14.9%) or a higher difference of oocytes retrieved (power: 22.3%). Although no statistical significance was reached, OCPs were observed to achieve higher average and positive difference of oocytes retrieved in the 2nd cycle.

Importance of a 5- versus 7-day pill-free interval in a GnRH antagonist protocol using corifollitropin alfa: a prospective cohort study in oocyte donors.

In this prospective cohort study, oocyte donors were recruited prospectively and assigned to receive corifollitropin alfa: 5 days after pill discontinuation (group D5; 42 donors), or 7 days after pill discontinuation (group D7; 50 donors) in a gonadotrophin-releasing hormone antagonist protocol. Fixed additional daily doses of 200 IU recombinent FSH (rFSH) were started after 7 days of corifollitropinalfa, until triggering. No significant differences in basal characteristics were observed between both groups. In group D5, mean (SD) total additional rFSH dose was 659 (452) IU; in group D7, total rFSH dose was 459 (356) IU (P = 0.022). Duration of stimulation was significantly longer in group D5 compared with group D7 (P = 0.002). No differences were found in total number of oocytes obtained. Total number of injections was significantly lower in group D7 compared with group D5 (9.8 [3.2] versus 11.9 [3.9], respectively; P = 0.004). Total cost of medication used for donor treatment was significantly higher in group D5 than in group D7 (P = 0.015). After more than 22 days of pill-taking, extending the pill-free interval to 7 days significantly reduces the total dose of gonadotrophins, duration of stimulation, total cost of medication and total number of injections.