Hysteroscopic Endometrial Fundal Incision versus Hysteroscopy Only in Oocyte Recipients: A Randomized Controlled Trial Assessing The Reproductive Outcomes.

BACKGROUND: Endometrial scratching (ES) remains controversial regarding its potential effectiveness in improving pregnancy rates. The objective of the present study was to assess the impact of endometrial fundal incision (EFI) during hysteroscopy on reproductive outcomes in a population of oocyte recipients. MATERIALS AND METHODS: A randomized controlled trial was conducted between 2020 and 2023 at the Third Department of Obstetrics and Gynecology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki and "Assisting Nature Centre of Reproduction and Genetics". The study population consisted of women who underwent hysteroscopy randomly assigned in a 1:1 ratio to either EFI (one to three months before embryotransfer with donor oocytes) or no intervention throughout office hysteroscopy. Clinical pregnancy and live birth rates were the primary outcomes. RESULTS: After the exclusion of patients with intraoperative diagnosed endometrial pathology, a total of 124 women underwent randomization. The pregnancy test was positive in 79% (n=49/62) of the women in the EFI compared to 59.7% (n=37/62) in the hysteroscopy-only group (P=0.019), while the live birth rates did not differ between the two groups (58.1%, n=36/62 vs. 51.6%, n=32/62, P=0.470). CONCLUSION: EFI during hysteroscopy seems to improve pregnancy rates in oocyte recipients without intrauterine pathology, while live birth rates are not affected by the EFI. These results should be interpreted with caution before the implementation of EFI in the routine in vitro fertilization (IVF) practice (registration number: NCT04580056).

Accuracy of Frozen Section Biopsy in the Diagnosis of Endometrial Cancer: A Systematic Review and Meta-Analysis.

The early and accurate diagnosis of endometrial cancer is of paramount importance for the survival of these patients. The aim of this study was to systematically appraise the available data regarding the accuracy of frozen section biopsy in diagnosing endometrial cancer. A thorough literature search was performed in PubMed/Medline, Scopus and the Cochrane Central Register of Controlled Trials databases from inception up to January 2023, with the use of specific, relevant key terms. A quality evaluation for each study was performed with the QUADAS-2 tool, whereas a bivariate random-effect model was performed to generate a summary receiver-operated curve. Heterogeneity was evaluated with Cochrane Q and Higgins' I2 statistics. Subgroup analyses were performed for studies focused on atypical hyperplasia and those focused on endometrial cancer. The search yielded 47 studies, involving 7790 patients with endometrial cancer. Among them, only 11 could be included in the quantitative analysis. QUADAS-2 evaluation resulted in rather high quality among the included studies. Quantitative synthesis resulted in a pooled sensitivity of 0.863 and pooled specificity of 0.916. The AUC was 0.948, the Q statistic was 10.488 (10 df, p = 0.399) and Higgins' I2 (4.655%) reported no significant heterogeneity. Subgroup analyses based on the diagnosis revealed a pooled sensitivity 0.886, specificity 0.862 and AUC 0.934 for endometrial cancer versus a sensitivity of 0.816, specificity of 0.962 and AUC 0.939 for atypical hyperplasia. Frozen section appears as a valid and reliable diagnostic tool for endometrial cancer. Its reliability seems to be even higher for the diagnosis of atypical hyperplasia. Therefore, this method may be considered in clinical practice and in settings with appropriate resources.

Hysteroscopic Endometrial Fundal Incision in Oocyte Recipients before Embryo Transfer May Improve Reproductive Outcomes: A Prospective Study.

BACKGROUND: Induced endometrial injury is a technique described that have positive impact on implantation. The aim of this study was to investigate whether hysteroscopic endometrial fundal incision (EFI) in oocyte recipients before embryo transfer increases pregnancy and live birth rates or not. MATERIALS AND METHODS: A prospective study was conducted between 2014 and 2019 at an in vitro fertilization (IVF) unit in Greece. As part of the protocol, hysteroscopy and EFI were offered to all the egg recipients and the outcomes compared with those from an older cohort from the same Unit not undergoing hysteroscopy. RESULTS: In total, 332 egg recipients participated in the study; 114 of them underwent EFI prior to embryo transfer. Both groups were similar in terms of age, years of infertility, duration of hormone replacement treatment (HRT) and number of blastocysts transferred. In the EFI group, minor anomalies were detected and treated in 6.1% (n=7) of the participants. Moreover, pregnancy test was positive in 73.7% of the women in the hysteroscopy group compared to 57.8% in the nonhysteroscopy group (P=0.004). Live birth rate was also higher (56.1 vs. 42.2%, P=0.016) in the EFI group compared to the non-hysteroscopy one. CONCLUSION: Apart from the obvious benefit of recognizing obscured anomalies, requiring surgical correction, it appears that in oocyte recipients prior to embryo transfer, EFI might improve uterine receptivity and reproductive outcomes.

Diagnostic hysteroscopy with endometrial fundal incision may improve reproductive outcomes in oocyte recipients after implantation failure.

OBJECTIVE: This study aimed to investigate whether hysteroscopy plus endometrial fundal incision (EFI) with endoscopic scissors can improve reproductive outcomes in oocyte recipients who have failed in their first egg donation cycle. METHODS: This was a prospective study (2014-2022) conducted in Assisting Nature Centre Reproduction and Genetics, Thessaloniki Greece, IVF Unit. The study population consisted of oocyte recipients with implantation failure in their first embryo transfer (ET) with donor eggs. All the recipients underwent routine evaluation during their early follicular phase, 1-3 months before the start of a new cycle with donor oocytes and were eligible to undergo EFI. RESULTS: During the study period, 218 egg recipients underwent egg donation; 126 out of 218 oocyte recipients (57.8%) did not achieve a live birth at the 1st ET. 109 of them had surplus embryos cryopreserved and underwent a second ET; 50 women consented for EFI. Both groups were similar in terms of age, years of infertility, duration of estrogen replacement protocol and number of transferred blastocysts (p>0.05). In the EFI group, 60% had normal intrauterine cavity, while 40% had minor anomalies. The pregnancy test was positive in 46% (n=23/50) in the EFI group compared with 27.1% (n=16/59) in the control group (p=0.04). Moreover, live birth rates were higher in the EFI group compared to the control group (38.0% vs. 20.3%; p=0.04). CONCLUSIONS: The findings of our study indicate that in oocyte recipients after implantation failure, diagnostic hysteroscopy plus EFI prior to subsequent ETmay increase pregnancy and live birth rates.

Endometrial scratching during hysteroscopy in women undergoing in vitro fertilization: a systematic review and meta-analysis.

Objective: Endometrial scratching (ES) during hysteroscopy before embryotransfer (ET) remains doubtable on whether it benefits the reproductive outcomes. The optimal technique is not clear and repeated implantation failure as a challenging field in in vitro fertilization (IVF) seems to be the springboard for clinicians to test its effectiveness. Methods: Medline, PMC, ScienceDirect, Scopus, CENTRAL, Google Scholar were searched from their inception up to April 2023 for studies to evaluate the effectiveness of adding endometrial scratching during hysteroscopy before ET. Results: The initial search yielded 959 references, while 12 eligible studies were included in the analyses, involving 2,213 patients. We found that hysteroscopy and concurrent ES before ET resulted in a statistically significant improvement in clinical pregnancy rate (CPR) [RR = 1.50, (95% CI 1.30-1.74), p < 0.0001] and live birth rate (LBR) [RR = 1.67, (95% CI 1.30-2.15), p < 0.0001] with no statistically significant difference on miscarriage rate [RR = 0.80 (95% CI 0.52-1.22), p = 0.30]. Conclusion: Our meta-analysis suggests that hysteroscopy with concurrent ES may be offered in IVF before ET as a potentially improving manipulation. Future randomized trials comparing different patient groups would also provide more precise data on that issue, to clarify specific criteria in the selection of patients. Systematic Review Registration: PROSPERO (CRD42023414117).

Epithelial Ovarian Cancer: A Five Year Review.

Ovarian cancer is a malignant disease that affects thousands of patients every year. Currently, we use surgical techniques for early-stage cancer and chemotherapy treatment combinations for advanced stage cancer. Several novel therapies are currently being investigated, with gene therapy and stem cell therapy being the corner stone of this investigation. We conducted a thorough search on PubMed and gathered up-to-date information regarding epithelial ovarian cancer therapies. We present, in the current review, all novel treatments that were investigated in this field over the past five years, with a particular focus on local treatment.

Laparoscopy in Pregnancy: A Comparative Review of National Guidelines.

Gynecological and general surgical conditions requiring surgical management during pregnancy constitute a medical challenge, which often entails the collaboration of numerous medical specialties. In recent years, laparoscopy in pregnancy has been accepted as a safe alternative to open surgery. This has led gynecological societies to conduct studies and issue guidelines related to laparoscopy in pregnancy, with a view to assisting and guiding clinicians and surgeons. The aim of this study was to review and compare the recommendations from various published national guidelines on laparoscopy in pregnant women. To that end, a descriptive review of guidelines from the British Society for Gynaecological Endoscopy (BSGE), the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES), the Society of Obstetricians and Gynaecologists of Canada (SOCG), and the Collège National des Gynécologues et Obstétriciens Français (CNGOF) was conducted. Regarding diagnosis, the SAGES and SOCG societies recommend ultrasound as the preferred and safe imaging technique during pregnancy. In terms of the optimal timing for laparoscopic intervention, BSGE and SAGES do not restrict the laparoscopic approach based on safety, depending on the gestation week, whereas SOCG and CNGOF propose early second trimester and first and second quarter of pregnancy respectively. There is an overall consensus regarding patient positioning, initial port placement, insufflation pressure during the operation, venous thromboembolic (VTE) prophylaxis, fetal heart monitoring, and tocolysis among the reviewed guidelines. Moreover, only the BSGE mentions the need for corticosteroids, magnesium sulfate, and anti-D prophylactic administration.

Investigation and Management of Recurrent Pregnancy Loss: A Comprehensive Review of Guidelines.

Importance: Recurrent pregnancy loss (RPL) is one of the most frustrating clinical entities in reproductive medicine requiring not only diagnostic investigation and therapeutic intervention, but also evaluation of the risk for recurrence. Objective: The aim of this study was to review and compare the most recently published major guidelines on investigation and management of RPL. Evidence Acquisition: A descriptive review of guidelines from the Royal College of Obstetricians and Gynaecologists, the European Society of Human Reproduction and Embryology, the American Society for Reproductive Medicine, the French College of Gynecologists and Obstetricians, and the German, Austrian, and Swiss Society of Gynecology and Obstetrics on RPL was carried out. Results: There is consensus among the reviewed guidelines that the mainstays of RPL investigation are a detailed personal history and screening for antiphospholipid syndrome and anatomical abnormalities of the uterus. In contrast, inherited thrombophilias, vaginal infections, and immunological and male factors of infertility are not recommended as part of a routine RPL investigation. Several differences exist regarding the necessity of the cytogenetic analysis of the products of conception, parental peripheral blood karyotyping, ovarian reserve testing, screening for thyroid disorders, diabetes or hyperhomocysteinemia, measurement of prolactin levels, and performing endometrial biopsy. Regarding the management of RPL, low-dose aspirin plus heparin is indicated for the treatment of antiphospholipid syndrome and levothyroxine for overt hypothyroidism. Genetic counseling is required in case of abnormal parental karyotype. The Royal College of Obstetricians and Gynaecologists, the European Society of Human Reproduction and Embryology, and the French College of Gynecologists and Obstetricians guidelines provide recommendations that are similar on the management of cervical insufficiency based on the previous reproductive history. However, there is no common pathway regarding the management of subclinical hypothyroidism and the surgical repair of congenital and acquired uterine anomalies. Use of heparin for inherited thrombophilias and immunotherapy and anticoagulants for unexplained RPL are not recommended, although progesterone supplementation is suggested by the American Society for Reproductive Medicine and the German, Austrian, and Swiss Society of Gynecology and Obstetrics. Conclusions: Recurrent pregnancy loss is a devastating condition for couples. Thus, it seems of paramount importance to develop consistent international practice protocols for cost-effective investigation and management of this early pregnancy complication, with the aim to improve live birth rates.

Hysteroscopic Identification of Intrauterine Pathology in Oocyte Donation Cycles: A Retrospective Study.

BACKGROUND: Hysteroscopy remains the gold standard for the diagnosis and treatment of intracavitary uterine anomalies. As for recipients where oocyte donation is mandatory, accurate evaluation of previously missed intrauterine pathology may be an important step to optimize implantation process. The aim of this study was to hysteroscopically assess the incidence of unidentified intrauterine pathology prior to embryo transfer in an oocyte recipient population. METHODS: A retrospective descriptive study was conducted between 2013 and 2022 at Assisting Nature In Vitro Fertilization (IVF) Centre in Thessaloniki, Greece. The study population consisted of oocyte recipient women who underwent hysteroscopy one-three months before embryo transfer. Furthermore, oocyte recipients after repeated implantation failure were investigated as a subgroup. Any identified pathology was treated accordingly. RESULTS: In total, 180 women underwent diagnostic hysteroscopy prior to embryo transfer with donor oocytes. The mean maternal age at the time of intervention was 38.9 (+5.2) years, while the mean duration of infertility was 6.03 (+1.23) years. Additionally, 21.7% (n=39) of the study population had abnormal hysteroscopic findings. In particular, congenital uterine anomalies (U1a: 1.1% {n=2}, U2a: 5.6% {n=10}, U2b: 2.2% {n=4}) and polyps (n=16) were the main findings in the sample population. Furthermore, 2.8% (n=5) had submucous fibroids and 1.1% (n=2) were diagnosed with intrauterine adhesions. Notably, in recipients after repeated implantation failure intrauterine pathology rates were even higher (39.5%). CONCLUSIONS: Oocyte recipients and especially those with repeated implantation failures probably have high rates of previously undiagnosed intrauterine pathology so, hysteroscopy would be justified in these subfertile populations.

Ovarian Stimulation with FSH Alone versus FSH plus a GnRH Antagonist for Elective Freezing in an Oocyte Donor/Recipient Programme: A Protocol for a Pilot Multicenter Observational Study.

Preliminary data have shown that it is possible to attempt in vitro fertilization (IVF) treatment in fresh cycles without the use of a gonadotropin-releasing hormone (GnRH) antagonist or any other medication to prevent the luteinizing hormone (LH) surge during ovarian stimulation. To date, there is no information on this topic in the context of a prospective controlled trial. However, as prevention of the LH surge is an established procedure in fresh cycles, the question is whether such a study can be performed in frozen cycles. We aim to perform a pilot study in order to compare the efficacy of a protocol using FSH alone with that of a protocol using follicle-stimulating hormone (FSH) plus a GnRH antagonist for controlled ovarian hyperstimulation (COH) in cycles of elective freezing in the context of a donor/recipient program. This is a seven-center, two-arm prospective pilot cohort study conducted at the respective Assisted Reproductive Units in Greece. The hypothesis to be tested is that an ovarian stimulation protocol that includes FSH alone without any LH surge prevention regimens is not inferior to a protocol including FSH plus a GnRH antagonist in terms of the clinical outcome in a donor/recipient model. The results of the present study are expected to show whether the addition of the GnRH antagonist is necessary in terms of the frequency of LH secretory peaks and progesterone elevations >1 ng/mL during the administration of the GnRH antagonist according to the adopted frequency of blood sampling in all Units.

Uterine Leiomyomas and Infertility: A Comparison of National and International Guidelines.

Uterine leiomyomas are the most common benign tumors of the female genital track, causing various symptoms and problems, including a possible impact on fertility. The relationship between fibroids and infertility has long been a debate among gynecologists. Management of fibroids in women with otherwise unexplained infertility worldwide lacks standardized, evidence-based guidelines. Therefore, a review of guidelines from the Royal Australian and New Zealand College of Obstetricians and Gynecologists, the American College of Obstetricians and Gynecologists, the Society of Obstetricians and Gynecologists of Canada, the Collège National des Gynécologues et Obstétriciens Français, and the American Society of Reproductive Medicine was conducted. There is agreement among all guidelines that the effect of fibroids on fertility is related to their position in the uterus and the alteration of the endometrial cavity. However, whether surgical intervention (laparotomy, laparoscopy, or hysteroscopy) is required varies among committees. More specifically, for submucous myomas, all guidelines agree that surgical intervention is needed. On the other hand, regarding intramural myomas, there is no consensus on what the approach may be. Novel treatments such as uterine artery embolization (UAE) and magnetic resonance-guided focused ultrasound surgery (MRgFUS) should only be used in clinical trial settings. Nevertheless, all guidelines agree that medical management of fibroids further delays efforts to conceive and has no role as a stand-alone treatment of fibroids; though, the use of GnRH analogues preoperatively can be useful to improve anemia and/or reduce fibroid volume. There is a need for updated international protocols to be introduced, in order to help clinicians dealing with fibroids and infertility to better suggest the optimal treatment.

Ovarian Hyperstimulation Syndrome after GnRH Agonist Triggering and Freeze-All Protocol? Never Not, Hardly Ever: A Systematic Review of Case Reports.

INTRODUCTION: Ovarian hyperstimulation syndrome (OHSS) is a severe complication associated with controlled ovarian stimulation (COS). GnRH agonist (GnRH-a) triggering is considered an efficient strategy to prevent OHSS in the high-risk patient. METHODS: We performed a review of 11 cases of early and severe OHSS following GnRH-a triggering and freeze-all protocol. Electronic databases were searched from inception of each database until October 2021, to identify case reports and case series that reported OHSS after GnRH-a triggering and freeze-all approach describing patient demographics, COS protocol, and patient outcomes. RESULTS: From the literature review, it is possible to suggest that (1) following GnRH-a triggering, the risk of early and severe OHSS is not totally cancelled; (2) despite it is not possible to predict the event, polycystic ovary syndrome is the most common risk factor; (3) the use of GnRH antagonist starting from the day of PU may represent a valid strategy for preventing OHSS in women with high-risk profile; (4) following the unexpected onset of OHSS, measuring serum levels of human chorionic gonadotropin (hCG) is helpful to exclude an inadvertent exogenous administration or a pregnancy. CONCLUSION: The statement that OHSS risk is eliminated when GnRH-a triggering, a freeze-all strategy, and no hCG in the luteal phase may generate the idea that this event cannot occur. Although rare, these cases have been observed in a relatively short period of time.

Agonist triggering in oocyte donation programs-Mini review.

Oocyte donation programs involve young and healthy women undergoing heavy ovarian stimulation protocols in order to yield good-quality oocytes for their respective recipient couples. These stimulation cycles were for many years beset by a serious and potentially lethal complication known as ovarian hyperstimulation syndrome (OHSS). The use of the short antagonist protocol not only is patient-friendly but also has halved the need for hospitalization due to OHSS sequelae. Moreover, the replacement of beta-human chorionic gonadotropin (b-hCG) with gonadotropin-releasing hormone agonist (GnRH-a) triggering has reduced OHSS occurrence significantly, almost eliminating its moderate to severe presentations. Despite differences in the dosage and type of GnRH-a used across different studies, a comparable number of mature oocytes retrieved, fertilization, blastulation, and pregnancy rates in egg recipients are seen when compared to hCG-triggered cycles. Nowadays, GnRH-a tend to be the triggering agents of choice in oocyte donation cycles, as they are effective and safe and reduce OHSS incidence. However, as GnRH-a triggering does not eliminate OHSS altogether, caution should be practiced in order to avoid unnecessary lengthy and heavy ovarian stimulation that could potentially compromise both the donor's wellbeing and the treatment's efficacy.

Preparation of the Endometrium for Frozen Embryo Transfer: A Systematic Review.

Despite the worldwide increase in frozen embryo transfer, the search for the best protocol to prime endometrium continues. Well-designed trials comparing various frozen embryo transfer protocols in terms of live birth rates, maternal, obstetric and neonatal outcome are urgently required. Currently, low-quality evidence indicates that, natural cycle, either true natural cycle or modified natural cycle, is superior to hormone replacement treatment protocol. Regarding warmed blastocyst transfer and frozen embryo transfer timing, the evidence suggests the 6th day of progesterone start, LH surge+6 day and hCG+7 day in hormone replacement treatment, true natural cycle and modified natural cycle protocols, respectively. Time corrections, due to inter-personal differences in the window of implantation or day of vitrification (day 5 or 6), should be explored further. Recently available evidence clearly indicates that, in hormone replacement treatment and natural cycles, there might be marked inter-personal variation in serum progesterone levels with an impact on reproductive outcomes, despite the use of the same dose and route of progesterone administration. The place of progesterone rescue protocols in patients with low serum progesterone levels one day prior to warmed blastocyst transfer in hormone replacement treatment and natural cycles is likely to be intensively explored in near future.

Endometrial changes in estrogen and progesterone receptor expression during implantation in an oocyte donation program.

Implantation is the final and most important stage of embryogenesis and is of paramount importance in achieving a successful pregnancy. Progesterone and estrogen are steroid hormones responsible for the regulation of the implantation window and the current study hypothesised that their receptors may be implicated in women undergoing oocyte donation. A total of 15 women aged 25-32 years old (mean ± SD, 28.9±2.89) undergoing oocyte donation were recruited into the present study. Participants underwent ovarian stimulation with gonadotrophin-releasing hormone antagonist and recombinant follicle-stimulating hormone. Endometrial aspiration biopsy was performed on the day of oocyte retrieval and after 5 days (on days 0 and 5, respectively). Endometrial histology and evaluation of estrogen receptor (ER)α and progesterone receptor (PR)-B were performed on days 0 and 5. The ER nodal staining percentage on day 0 was age-associated, with patients aged <30 years demonstrating 100% staining and those aged >30 years exhibiting 90% staining. Pathological staining revealed statistically significant differences between days 0 and 5 following all staining procedures. Wilcoxon signed-rank test resulted in the following P-values, for ER (nodes % and stromal %) day 0/5, P=0.0001; for PR (nodes % and stromal %) day 0/5, P=0.0001 and P=0.035, respectively; for ER (grade nodes and stromal %) day 0/5, P=0.0001; and PR (grade nodes and stromal %) day 0/5 P=0.0001 and P=0.016, respectively. Synchronization between blastocyst development and the acquisition of endometrial receptivity is a prerequisite for the success of in vitro fertilisation (IVF). Aside from the recent discovery of molecules that are considered crucial for successful embryo implantation, assessing the functional characteristics of the endometrium may offer unique insights into this process, thus improving IVF results.

Evaluation of the safety and efficacy of corifollitropin alfa combined with GnRH agonist triggering in oocyte donation cycles. A prospective longitudinal study.

OBJECTIVE: In order to help make the dream of parenthood come true for oocyte acceptors, it is essential that the procedure is not dangerous or unpleasant for oocyte donors. The aim of this study was to identify differences in safety, efficacy and patient acceptability between a traditional stimulation antagonist protocol with recombinant-FSH (rFSH) with hCG-triggering, compared with an innovative antagonist protocol with corifollitropin alfa (Elonva®) plus GnRH agonist triggering in oocyte donors. METHODS: A prospective longitudinal study was conducted at an in vitro fertilization center in Greece. The same eighty donors underwent two consecutive antagonist stimulation schemes. Primary outcomes were patient satisfaction (scored by a questionnaire) and delivery rate per donor. Secondary outcomes were mean number of cumulus-oocyte-complexes, metaphase II (MII) oocytes and ovarian hyperstimulation syndrome (OHSS) rate. RESULTS: Donors reported better adherence and less discomfort with the corifollitropin alpha + GnRH agonist-triggering protocol (p<0.001). No significant differences were identified in the clinical pregnancy rate per donor (p=0.13), the delivery rates, the number of oocytes (p=0.35), the number of MII oocytes (p=0.50) and the number of transferred embryos, between the two protocols. However, the luteal phase duration was significantly shorter (p<0.001) in the corifollitropin alpha + GnRH agonist-triggering protocol. Moreover, three cases of moderate OHSS (3.75%) were identified after hCG triggering, whereas no case of OHSS occurred after GnRH agonist ovulation induction (p=0.25). CONCLUSION: The use of corifollitropin alpha combined with a GnRH agonist for triggering is a safe, effective and acceptable protocol for oocyte donors.

COVID-19 and assisted reproductive technology services: repercussions for patients and proposal for individualized clinical management.

The prolonged lockdown of health services providing high-complexity fertility treatments -as currently recommended by many reproductive medicine entities- is detrimental for society as a whole, and infertility patients in particular. Globally, approximately 0.3% of all infants born every year are conceived using assisted reproductive technology (ART) treatments. By contrast, the total number of COVID-19 deaths reported so far represents approximately 1.0% of the total deaths expected to occur worldwide over the first three months of the current year. It seems, therefore, that the number of infants expected to be conceived and born -but who will not be so due to the lockdown of infertility services- might be as significant as the total number of deaths attributed to the COVID-19 pandemic. We herein propose remedies that include a prognostic-stratification of more vulnerable infertility cases in order to plan a progressive restart of worldwide fertility treatments. At a time when preventing complications and limiting burdens for national health systems represent relevant issues, our viewpoint might help competent authorities and health care providers to identify patients who should be prioritized for the continuation of fertility care in a safe environment.

Highlighting the importance of multidisciplinary approach: A rare case of primary periurethral poorly differentiated carcinoma.

OBJECTIVE: Tumors in the periurethral area can be a rare clinical entity with many difficulties not only in the diagnosis, as well as in the treatment plan. Skene's gland adenocarcinoma accounts for less than 0.003% of all female urethral malignant neoplasms. CASE REPORT: This report describes an extremely rare case of woman with a poorly differentiated carcinoma arising from the periurethral glands. CONCLUSIONS: Reporting of such rare cases enhance the understanding of the biological behavior of such tumors and the best treatment plan as well. This case report highlights the need for multidisciplinary approach of such rare cases, the lack of experience for such cases and the fact that the optimal treatment plan is very critical for the best prognosis of these patients.

In Freeze-All Strategy, Cumulative Live Birth Rate (CLBR) Is Increasing According to the Number of Blastocysts Formed in Women <40 Undergoing Intracytoplasmic Sperm Injection (ICSI).

Background: Elective freezing of all embryos, followed by frozen-thawed ET cycles emerged to prevent risk of Ovarian Hyperstimulation Syndrome and to allow endometrium recovery after Controlled Ovarian Stimulation, leading to better IVF outcomes. Blastocyst Freeze-all policy can minimize the number of abnormal embryos and consequently failed ETs, but its efficacy in terms of cumulative rates has not been studied yet. Methods: A prospective cohort observational study was carried out in Assisting Nature, Center of Assisted Reproduction and Genetics, in Thessaloniki, Greece from January 2014 until December 2017. 244 patients- normal or high responders- underwent COS with recFSH and Freeze-all policy with blastocyst culture. The included patients were 18-39 years and achieved clinical pregnancy and/or live birth or had all their vitrified blastocysts transferred in subsequent frozen-thawed cycles. Women were divided into four groups (group A: 1-2 blastocysts frozen; group B: 3-4; group C: 5-6; group D ≥7 blastocysts frozen) or seven groups (group I: 1-2 blastocysts frozen, group II: 3, group III: 4, group IV: 5, group V: 6, group VI: 7; group VII: ≥8 blastocysts frozen), according to the numerical range or to the absolute number of vitrified blastocysts, respectively. Results: The main outcome of the study was the CLBR achieved by frozen-thawed ETs, according to the number of the vitrified blastocysts. Higher CLBR are expected, when at least 3 blastocysts are formed (group B: 65.2%) and at least 2 frozen-thawed ETs are performed, reaching highest rates (88%) by group D (≥7 vitrified blastocysts). Similarly, CLBR is significantly increasing with the absolute number of the vitrified blastocysts, ranging from 20%, when 1-2 blastocysts are vitrified (group I) to 82.4% when ≥8 blastocysts are available. Conclusions: A higher number of vitrified blastocysts is associated with higher CLBR in women <40 years old- normal/high responders- following Freeze-all policy. Adopting Freeze-all strategy after blastocyst culture can contribute to improve delivery outcome after IVF, in terms of CLBR. The number of the total cryopreserved blastocysts produced might reflect the quality of the oocyte and can successfully predict the pregnancy outcome. The blastulation rate can be a robust criterion to segment or not an IVF cycle.

COMFFETI, Combined Fresh and Frozen Embryo Transfers per Individual: A New Index of Quality Control for The Performance of emberyologic Labs in The Emerging Era of Segmentation of Cycle and Freeze-All Strategy.

The efficacy of in vitro fertilization (IVF) for treating human infertility has only one final efficacy index and that is the achievement of a delivery. However, with the evolution of the freeze-all strategy, a new problem is arising for evaluating the performance of an embryological team. The aim of the study was to present a new representative index, combining fresh and frozen embryo transfer success rates. In this opinion article, apart from the effectiveness of managing fresh gametes and embryos, we wish to evaluate the efficacy of the processes of both freezing and thawing of the produced embryos. The reporting of pregnancy rates of an IVF unit in the past was primarily laying in the fresh embryo transfer (ET) pregnancy rates. Now with the most frequent utilization of freeze-all strategy, it does not seem logical to report only on poor prognosis patients as all the good cases are postponed for thawed cycles. Ongoing implementation of the freeze-all strategy has indicated the need to establish a new representative index that may combine the success of both fresh and frozen cycles performed in the same woman; an index that may not be biased by the policy of an IVF center towards or against the freeze-all strategy. This newly proposed index, which is referred to as COMFFETI (Combined Fresh #38; Frozen Embryo Transfers per Individual), describes the optimal way to report final reproductive outcomes in the present opinion article.