When the Embryo Meets the Endometrium: Identifying the Features Required for Successful Embryo Implantation.

Evaluation of the optimal number of embryos, their quality, and the precise timing for transfer are critical determinants in reproductive success, although still remaining one of the main challenges in assisted reproduction technologies (ART). Indeed, the success of in vitro fertilization (IVF) treatments relies on a multitude of events and factors involving both the endometrium and the embryo. Despite concerted efforts on both fronts, the overall success rates of IVF techniques continue to range between 25% and 30%. The role of the endometrium in implantation has been recently recognized, leading to the hypothesis that both the "soil" and the "seed" play a central role in a successful pregnancy. In this respect, identification of the molecular signature of endometrial receptivity together with the selection of the best embryo for transfer become crucial in ART. Currently, efforts have been made to develop accurate, predictive, and personalized tests to identify the window of implantation and the best quality embryo. However, the value of these tests is still debated, as conflicting results are reported in the literature. The purpose of this review is to summarize and critically report the available criteria to optimize the success of embryo transfer and to better understand current limitations and potential areas for improvement.

Systemic vascular resistance may influence the outcome of in vitro fertilization.

Introduction: The number of pregnancies obtained through in vitro fertilization (IVF) techniques are increasing, and only few studies have investigated hemodynamic variations in women undergoing IVF techniques. The aim of this study was to evaluate the hemodynamic parameters in women undergoing IVF, to assess a possible correlation between hemodynamics and embryo implantation.Methods: 45 normotensive non-obese women, age ≤ 43 years, with idiopathic or tubal infertility, referred to the Reproductive Physiopathology and Andrology Unit, Sandro Pertini Hospital, Rome, during the period 2020/2021, underwent IVF techniques. All women were evaluated with Ultra Sonic Cardiac Output Monitor (USCOM) to detect hemodynamic parameters at two different stages: at the mid-luteal phase, before the beginning of IVF, and at the day of embryo transfer (dET). All demographics and hormonal parameters in both groups were comparable. The hemodynamic parameters were compared between women with a positive ß-HCG test vs. those testing negative.Results: 11 out of 45 (24,5%) women obtained positive ß-HCG test. All demographics and hormonal parameters were comparable in both groups. Women with a positive ß-HCG test showed statistically lower systemic vascular resistance (SVR) at mid-luteal phase (868.61 ± 100.1 vs. 1009 ± 168.4) and dET (818,9 ± 104.5 vs 1038.52 ± 150.82 dynes × s/cm5).Conclusions: Hemodynamic assessment can identify a more favorable pre-pregnancy cardiovascular adaptation. Embryo implantation might be positively influenced by the hemodynamic parameters, e.g. lower SVR, before the beginning of IVF techniques, and during the window of implantation.

Love in the Time of COVID-19: Sexual Function and Quality of Life Analysis During the Social Distancing Measures in a Group of Italian Reproductive-Age Women.

BACKGROUND: The beginning of 2020 was characterized by the COVID-19 pandemic. The world governments have adopted restrictive measures to reduce the spread of infection. These measures could affect the sexual function and quality of life of women living with their partner. AIM: The aim is to assess the impact of the social distancing measures caused by the COVID-19 pandemic on sexual function and quality of life of noninfected reproductive-age women, living with their sexual partner. METHODS: Observational analysis on sexually active women, living with their partner, and without COVID-19 infection was performed. The population previously answered FSFI, FSDS, and SF-36 questionnaires. 4 weeks after the introduction of the restrictive measures, these women were invited to complete the same questionnaires by e-mail for an evaluation during the COVID-19 outbreak. MAIN OUTCOME MEASURES: The primary endpoint was the assessment of the women's sex function change during the social restriction period, by analyzing the FSFI and FSDS questionnaires. The secondary endpoint was the evaluation of the impact on the quality of life calculated by the SF-36 questionnaire. RESULTS: 89 patients were considered. The median age was 39 (28-50) years. Mean sexual intercourses/month decreased from 6.3 ± 1.9 to 2.3 ± 1.8, mean difference: -3.9 ± 1.2. FSFI decreased significantly (29.2 ± 4.2 vs 19.2 ± 3.3, mean difference: -9.7 ± 2.6) and FSDS increased significantly (9.3 ± 5.5 vs 20.1 ± 5.2, mean difference: 10.8 ± 3.4). The SF-36 showed a significant change from 82.2 ± 10.2 to 64.2 ± 11.8 4 weeks after the introduction of the restrictive measures; mean difference: -17.8 ± 6.7. The univariable analysis identified working outside the home, university educational level, and parity ≥1 as predictive factors of lower FSFI. In multivariable analysis, working outside the home and combination of working outside the home + university educational level + parity ≥1 were the independent factors of a lower FSFI. CLINICAL IMPLICATION: The negative impact of the COVID-19 epidemic period on sexual function and quality of life in women shows how acute stress might affect the psychological state. Thus, psychological or sexual support could be useful. STRENGTHS AND LIMITATIONS: To our knowledge, this study is the first that analyzes the change in sexual activity in women during the COVID-19 outbreak period. The limitations were the low number of the analyzed participants, psychological tests were not included, and no data were collected on masturbation, self-heroism, solitary, and nonpenetrative sex. CONCLUSION: The COVID-19 epidemic and the restrictive social distancing measures have negatively influenced the sexual function and quality of life in not-infected reproductive-age women who live with their sexual partners. Schiavi MC, Spina V, Zullo MA, et al. Love in the Time of COVID-19: Sexual Function and Quality of Life Analysis During the Social Distancing Measures in a Group of Italian Reproductive-Age Women. J Sex Med 2020;17:1407-1413.

Low endometrial beta-catenin and cadherins expression patterns are predictive for primary infertility and recurrent pregnancy loss.

Inadequate uterine receptivity is responsible for two-third of implanting failures. Aim of the study was to investigate the role of epithelial adherence and tight-junction molecules expressed by human endometrium in predicting womens' fertility outcome. A total of 76 consecutive women, including 24 fertile (G1), 40 primary infertile (G2), and 12 recurrent pregnancy loss (RPL, G3) women, who underwent diagnostic hysteroscopy plus endometrial biopsy between 2005 and 2016 at the Gynecology Division of Sant'Andrea Hospital, Sapienza University of Rome, in Italy, were retrospectively identified and included into the study. Endometrial biopsies were assessed for the immunohistochemical expression of beta-catenin (ß-catenin), E-cadherin and K-cadherin biomarkers. Expression profiles were compared between the three groups of patients and were correlated with patients' fertility outcome. In infertile patients there was a significant lower endometrial expression of ß-catenin (p = .001), E-cadherin (p = .001) and K-cadherin (p = .002), compared to the fertile ones. Furthermore, ß-catenin and E-cadherin intensity gradients of expression at glandular level were found totally reversed in infertile patients. Significant lower expression levels of K-catenin (p = .016) and E-cadherin (p < .0001) at glandular level were found in RPL patients. Results showed that the low endometrial expression of ß-catenin, E-cadherin and K-cadherin were associated to fertility-related problems, such as primary intertility and RPL.

Molecular Signaling Regulating Endometrium-Blastocyst Crosstalk.

Implantation of the embryo into the uterine endometrium is one of the most finely-regulated processes that leads to the establishment of a successful pregnancy. A plethora of factors are released in a time-specific fashion to synchronize the differentiation program of both the embryo and the endometrium. Indeed, blastocyst implantation in the uterus occurs in a limited time frame called the "window of implantation" (WOI), during which the maternal endometrium undergoes dramatic changes, collectively called "decidualization". Decidualization is guided not just by maternal factors (e.g., estrogen, progesterone, thyroid hormone), but also by molecules secreted by the embryo, such as chorionic gonadotropin (CG) and interleukin-1ß (IL-1 ß), just to cite few. Once reached the uterine cavity, the embryo orients correctly toward the uterine epithelium, interacts with specialized structures, called pinopodes, and begins the process of adhesion and invasion. All these events are guided by factors secreted by both the endometrium and the embryo, such as leukemia inhibitory factor (LIF), integrins and their ligands, adhesion molecules, Notch family members, and metalloproteinases and their inhibitors. The aim of this review is to give an overview of the factors and mechanisms regulating implantation, with a focus on those involved in the complex crosstalk between the blastocyst and the endometrium.

Evaluation of Renal Function with Urinary NGAL and Doppler Ultrasonography in ICU Patients: A 1-Year Observational Pilot Study.

BACKGROUND: We estimated the diagnostic accuracy of urinary NGAL for the diagnosis of AKI. METHODS: Urinary NGAL and Creatinine were measured daily for up to 3 days. Doppler ultrasonography was performed within 24 h of admission and for the following 3 days. RESULTS: Of the 21 patients, 44% had AKI during their ICU stay. The AKI group presented with higher values of serum Creatinine, renal length, MDRD as well as SAPS II already at admission. Urinary NGAL was significantly higher among patients with AKI and patients AKI-no at T0 (p < 0.0001) and increased steadily on T1 and T2. Urinary NGAL seemed to be a notable diagnostic marker for AKI from the first measurement (T0) with an area under the ROC of 0.93 (95% CI = 0.78-0.99) with a sensitivity of 99%. RRI levels were slightly higher in the AKI group at each time and increased gradually from T0 to T2 but reached statistical significance only at T2 (p = 0.02). Renal length and SAPS II at T0 showed high AuRoc and sensitivity. CONCLUSIONS: Urinary NGAL is a valuable marker for AKI in intensive care settings. It seemed that a pre-existing chronic renal disease, the SAPS II and the NGAL at admission represented the principal predictors of AKI.

Luteal phase support in assisted reproductive technology centers: Italian survey.

BACKGROUND: In assisted reproductive cycles (ART), the fine balance of controlling corpus luteum function is severely disrupted. To challenge this iatrogenic deficiency, clinicians aim to provide exogenous support. Several reviews have investigated progesterone route of administration, dosage and timing. METHODS: A survey about luteal phase support (LPS) after ovarian stimulation was conducted among doctors in charge in Italian II-III level ART centers. RESULTS: With regards to the general approach to LPS, 87.9% doctors declare to diversify the approach; the reasons for diversifying (69.7%) were based on the type of cycle. For all the most important administration routes (vaginal, intramuscular, subcutaneous) it appears that in frozen cycles there is a shift towards higher dosages. The 90.9% of the centers use vaginal progesterone, and when a combined approach is required, in 72.7% of cases vaginal administration is combined with injective route of administration. When Italian doctors were asked about the beginning and duration of LPS, 96% of the centers start the day of the pickup or the day after, while 80% of the centers continue LPS until week 8-12. The rate of participation of the centers confirms the low perceived importance of LPS among Italian ART centers, while may be considered quite surprising the relatively higher percentage of centers that measures P level. Tailorization to women's needs is the new objective of LPS: self-administration, good tolerability are the main aspects for Italian centers. CONCLUSIONS: In conclusion, results of Italian survey are consistent to results of main international surveys about LPS.

Spontaneous Pregnancy after 4D-Hysterosalpingo-Sonography (HyCoSy) in the Same Menstrual Cycle: A Case Report and an Updating Review of the Current Literature regarding the Positive Impact of Tubal Flushing Effect on Fertility.

Infertility is increasing worldwide, as well as in Italy, and fallopian tube pathology represents one of the most impacting causes of infertility for multiple women. Indeed, tubal patency assessment is a crucial step in medical evaluation for women attending an in vitro fertilization (IVF) center. Currently, different methods for tubal investigation are available, such as chromosalpingoscopy, hysterosalpingography (HSG), and hysterosalpingo-contrast sonography (HyCoSy). This diagnostic exam is performed by ultrasonography and an air-water-based contrast agent represented by air-water, or foam solution (HyFoSy). An additional side benefit of these assessment tests is a fertility-enhancing effect, thanks to a positive effect defined as "tubal flushing," which in current literature is more strongly associated with HyFoSy with respect to HyCoSy. In this report, we present a case of a 34-year-old woman presented to our attention at the Reproductive and Physiopathology Unit of Sandro Pertini Hospital, Rome, in 2023, with unexplained infertility for 3.1 years of free sexual intercourse with a partner who did not report sperm abnormalities. Subsequently, in this exam, the woman spontaneously conceived in the same menstrual cycle that the 4D-HyCoSy was performed, without any additional fertility enhancement interventions. In this case report, we also include an updating review of the current literature regarding the insurgence of spontaneous pregnancy after this technique in order to explore the physiopathological and etiopathogenetic mechanisms underlying the achievement of spontaneous pregnancy and to confront our case with other recent works published. According to our clinical experience and the current literature, 4D-HyCoSy is the easiest, safest, and cheapest diagnostic exam for investigating tubal patency, which can lead to medical success in some cases of "unexplained infertility" as the achievement of a spontaneous pregnancy.

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Increased costs of perioperative risk assessment for thyroid surgery in elderly people (over 80 years) presenting with benign disease.

BACKGROUND/OBJECTIVES: Evaluate how surgical treatment of benign thyroid disease in elderly people is prone to induce an increase of costs in the next future due to the aging process of the population. METHODS: A retrospective analysis has been performed on a total of 116 patients operated between January 2007 and September 2011, divided in a group of 58 patients aged over 80 years (Group A) and 58 patients younger than 80 years (Group B). The analyzed data included age, preoperative diagnosis, severe co-morbidities, procedures other than standard needed to evaluate anaesthesiological risk, postoperative hospital stay, complications, duration of postoperative intensive care monitoring, pathologic characteristics, and costs of anaesthesiological risk assessment. RESULTS: Statistical analysis of collected data showed that the costs related to perioperative risk assessment (p value < 0.001) and the duration of hospital stay (p value < 0.001) were higher in Group A than in Group B. Instead, surgery-related complications were not statistically different. CONCLUSIONS: Despite feasibility and safety of modern surgical techniques, indications for surgery in elderly patients affected by benign thyroid disease should be reserved mainly for those patients with severe medical necessity.

Hysterosalpingocontrast sonography (HyCoSy): evaluation of the pain perception, side effects and complications.

BACKGROUND: Tubal and uterine cavity diseases commonly compromise female fertility. At the present time, hysteroscopy, laparoscopy with chromopertubation and RX-Hysterosalpingography (RX-HSG) are widely accepted screening procedures enabling the effective assessment of both tubal patency and uterine cavity. Nevertheless, consistent evidence supports the reliability of Hysterosalpingocontrast sonography (HyCoSy) in uterine cavity and tubal patency investigation, as a part of the standard infertility work-up. This prospective study was aimed at evaluating the tolerability of the technique as well as the incidence of related side effects and complications in a large series of infertile patients. METHODS: Pain perception of 632 infertile women was measured by means of an 11-point numeric rating scale. Side effects and late complications were also recorded. RESULTS: The mean numeric rating scale was 2.15 ± 2.0 SD. Most of the patients (374/632, 59.17%) rated HyCoSy as a non-painful procedure, whereas 24.36% (154/632) women reported mild pelvic pain and 9.96% (63/632) classified the discomfort as "moderate". Only 6.48% (41/632) of the patient population experienced severe pelvic pain. Fifteen (2.37%) patients required drug administration for pain relief. Twenty-six patients (4.11%) showed mild vaso-vagal reactions that resolved without atropine administration. No severe vaso-vagal reactions or late complications were observed. CONCLUSIONS: HyCoSy is a well-tolerated examination and the associated vagal effects are unusual and generally mild. Consequently, we support its introduction as a first-line procedure for tubal patency and uterine cavity investigation in infertile women.

The Impact of Nutritional Therapy in the Management of Overweight/Obese PCOS Patient Candidates for IVF.

Polycystic ovary syndrome (PCOS) is the most common female endocrine disorder, and it has two main pathological aspects: reproductive and metabolic. Overweight/obesity is a risk factor in terms of adverse effects during hormone stimulation, a reduced response to ovulation induction regimens, reduced success of IVF, and an increased risk of obstetric complications. To resolve this vicious cycle of pathological events, weight loss and lifestyle modifications are promising strategies. Among these possible approaches, the consumption of a very-low-calorie ketogenic diet (VLCKD) or Mediterranean diet (MD) represents a valid option. In our study, 84 obese/overweight PCOS patients were recruited to evaluate the effects induced by the VLCKD and MD on weight, hormonal, and metabolic parameters. BMI decreased significantly among the VLKCD patients compared to the MD patients (both presenting p values < 0.0001 at 90 and 120 days), and a significant reduction in body circumference was observed. At the same time, HOMA index values statistically decreased for the VLCKD patients compared to those on the MD (p value < 0.001 at 90 days and p value < 0.05 at 120 days), and this phenomenon was also observed for AFC at 90 and 120 days (both p values < 0.001) and AMH at 90 days (p value < 0.05). Interestingly, the ovarian hyperstimulation syndrome (OHSS) incidence was statistically lower in the VLKCD patients compared to the MD patients (p < 0.001). We state that these dietary regimes may improve anthropometric parameters (such as BMI) and women's reproductive health, restore menstrual regularity, and reduce the risk of OHSS. Regarding the different nutritional therapies, the results suggest that the VLCKD is an optimal choice for entry into IVF, especially in terms of the time range in which these results are achieved.

Sexual function analysis and clitoral vascularization in postmenopausal women with genitourinary syndrome treated with ospemifene.

BACKGROUND: The aim of this study was to evaluate the efficacy of ospemifene in the Vaginal Health Index (VHI), in the vulvovaginal vascular perfusion, and to assess its impact on quality of life and sexual function. METHODS: Among 52 eligible patients, 43 consecutive postmenopausal patients affected by vulvo-vaginal atrophy (VVA), or genitourinary syndrome (GSM) were evaluated. VVA evaluation and ultrasound of the vulvo-vaginal vascularization by sampling the Pulsatility Index (PI) of clitoris dorsal artery were performed before and after 3 months-treatment with ospemifene. The 36-Item Short Form Survey (SF-36) for the quality-of-life assessment before and after 3 months were available for all women; instead, Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale (FSDS) questionnaires for the sexual function evaluation were performed for sexually active women in the study. The Patient Impression of Global Improvement (PGI-I) after 3 months of treatment was also calculated. RESULTS: The number of sexually active women significantly increased after 3 months (26 [60.46%] vs. 35 [81.39%]; P=0.01). The mean number of intercourses during the treatment increased (12.87±3.43 vs. 15.79±3.12, P=0.03). The PI of clitoris dorsal artery has significantly changed before and after treatment respectively (PI [1.69±0.42 vs. 1.28±0.45, P=0.001] RI [0.74±0.11 vs. 0.54±0.15, P=0.001]). The FSFI, FSDS and SF-36 Questionnaires scores showed a significant improvement after 3 months. VHI and PI were the independent factors of a lower FSFI after 3 months of treatment at multivariate analysis. CONCLUSIONS: Ospemifene improve the VHI and vulvovaginal vascular perfusion demonstrating a positive impact on sexual function and quality of life.

Iodized Salt May Not Be Sufficient to Guarantee an Adequate Iodine Intake in Pregnant Women.

Adequate iodine intake is of crucial importance in pregnancy to meet the thyroid hormone needs of both mother and fetus. In the present study, undertaken as a part of the surveillance actions following the introduction in Italy of a national salt iodination program in 2005, the iodine intake was investigated in 123 pregnant women and 49 control women living in the same area of central Italy. All the participants were screened for urinary iodine concentration (UIC), serum level of thyrotropin, free-thyroxine, free-triiodothyronine, and thyroid volume. Moreover, they were provided with a questionnaire on the use of iodine-containing salt or supplements. Control women had a median UIC of 102 µg/L, consistent with an iodine sufficiency, while in pregnant women the median UIC value was 108 µg/L, lower than the endorsed UIC of 150 µg/L. In addition, pregnant women showed a significantly increased median thyroid volume compared to controls. Interestingly, the median UIC did not differ between pregnant women not using iodine-containing salt or supplements and those regularly consuming iodized salt alone, while pregnant women with a daily intake of iodine-containing supplements had an adequate median UIC (168 µg/L). In conclusion, the data reported here showed that pregnant women and their fetuses are still exposed to the detrimental effects of iodine deficiency and that the consumption of iodine-containing supplements should be recommended in pregnancy.

Pretreatment with myo-inositol in non polycystic ovary syndrome patients undergoing multiple follicular stimulation for IVF: a pilot study.

BACKGROUND: Aim of this pilot study is to examine the effects of myo-inositol administration on ovarian response and oocytes and embryos quality in non PolyCystic Ovary Syndrome (PCOS) patients undergoing multiple follicular stimulation and in vitro insemination by conventional in vitro fertilization or by intracytoplasmic sperm injection. METHODS: One hundred non-PCOS women aged <40 years and with basal FSH <10 mUI/ml were down-regulated with triptorelin acetate from the mid-luteal phase for 2 weeks, before starting the stimulation protocol for oocytes recovery. All patients received rFSH, at a starting dose of 150 IU for 6 days. The dose was subsequently adjusted according to individual response. Group B (n=50) received myo-inositol and folic acid for 3 months before the stimulation period and then during the stimulation itself. Group A (n-50) received only folic acid as additional treatment in the 3 months before and through treatment. RESULTS: Total length of the stimulation was similar between the two groups. Nevertheless, total amount of gonadotropins used to reach follicular maturation was found significantly lower in group B. In addition, the number of oocytes retrieved was significantly reduced in the group pretreated with myo-inositol. Clinical pregnancy and implantation rate were not significantly different in the two groups. CONCLUSIONS: Our findings suggest that the addition of myo-inositol to folic acid in non PCOS-patients undergoing multiple follicular stimulation for in-vitro fertilization may reduce the numbers of mature oocytes and the dosage of rFSH whilst maintaining clinical pregnancy rate. Further, a trend in favor of increased incidence of implantation in the group pretreated with myo-inositol was apparent in this study. Further investigations are warranted to clarify this pharmacological approach, and the benefit it may hold for patients.

Management of women with uterine fibroids in reproductive center: retrospective analysis of clinical and reproductive outcomes.

BACKGROUND: Uterine fibroids are the most common benign tumor in women. According to literature, submucosal myomas have a negative effect on reproductive outcomes in women undergoing assisted reproductive techniques (ART) but there are fewer data concerning intramural fibroids. During last years, ulipristal acetate (UPA) 5 mg was widely used as medical option of fibroid's treatment, but from 2020, the Pharmacovigilance Risk Assessment Committee (PRAC) has revoked the marketing authorization after some cases of liver toxicity. METHODS: In this observational, retrospective study we collected data from a sample of 23 women affected by symptomatic uterine fibroids (from type 1 to type 7 according FIGO classification) followed in our center for assisted reproduction from 2016-2019. All patients received 5 mg/day UPA for three months, followed by two months of wash-out therapy. A group of 13 women treated with UPA, with intramural fibroid not distorting the uterine cavity, after wash-out therapy, affected by tubal or idiopathic factors of infertility too, underwent ART. We also evaluated a control group of women, not affected by fibroids, randomly selected from a general group of our ART patients, similar by age, BMI, and cause of infertility only idiopathic or tubal factors. We evaluated the impact of UPA on reduction of fibroid volume, symptomatology and distortion of the cavity in all the women treated, and the IVF (in-vitro fertilization) outcome between the fibroid group of women affected by intramural fibroids who underwent ART, and the control group. RESULTS: In all the women treated with UPA the overall median fibroid volume pretreatment was 45.168±35.360 mm3, that decreased to a mean value of 22.592±22.116 mm3 post one cycle of UPA, with an overall mean decrease of -22.586 mm3 (of 49%) statistically significant (P=0.00001). After treatment, the distortion of the uterine cavity reduced in high percentage of cases: 85,71% (type 1-2), χ2 difference in respect to the value pretreatment of 0.3941, and 86.96% of patients subjectively referred an improvement in the symptomatology. In the group of 13 women that undergone ART, after one IVF cycle for each patient, we obtained 61% of positivity of dosage of beta human chorionic gonadotropin (hCG) after UPA treatment, and we obtained a similar value in the control group. CONCLUSIONS: In our little sample we have observed that UPA represented a valid non-invasive medical treatment strategy for fibroids in women candidate for (IVF, not only in women affected by sub-mucosal, but also by intramural fibroids not distorting uterine cavity. After a single, three months course of treatment, we obtained good results in terms of reduction of fibroid's volume and improvement of symptomatology, without side effects, preparing a more favorable environment for ART.

Prospective multicenter non-interventional real-world study to assess the patterns of use, effectiveness and safety of follitropin delta in routine clinical practice (the PROFILE study).

Objective: To observe the real-world utilization patterns, effectiveness and safety profile of follitropin delta in women ≥18 years naïve to ovarian stimulation undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Design: Prospective, multinational, multicenter, observational study. All IVF/ICSI treatment protocols were conducted according to routine clinical practice, including undertaking fresh/frozen transfers. Outcomes included use of dosing algorithm, follitropin delta dosing patterns, ovarian response, pregnancy rates and adverse drug reactions (ADRs). Results: The first ovarian stimulation cycle using follitropin delta was initiated in 944 women. Mean baseline demographics were: age, 33.5 ± 4.7 years; bodyweight, 67.1 ± 13.6 kg; anti-Müllerian hormone, 20.3 ± 16.1 pmol/L (2.84 ± 2.25 ng/mL). The dosing algorithm was used to calculate the follitropin delta daily starting dose in 893/944 women (94.5%). The mean difference between the calculated and prescribed daily dose was small (0.2 ± 1.40 µg). The mean daily starting follitropin delta dose was 10.4 ± 2.72 µg and the mean total dose administered was 104 µg. Follitropin delta dose adjustments were reported for 57/944 (6.0%) women. The mean number of retrieved oocytes was 10.1 ± 7.03. Ongoing pregnancy at 10-11 weeks was reported for 255 women (27.0% per initiated cycle and 43.1% per fresh transfer [n=592]). Cumulative ongoing pregnancy rate after fresh and/or frozen transfer was 36.4% (344/944). Four women discontinued follitropin delta due to ADRs. Ovarian hyperstimulation syndrome (OHSS) was the most frequently reported ADR (n=37 [3.9%]); most cases of OHSS were of mild or moderate intensity (n=30 [3.2%]). Conclusions: This large real-world study of follitropin delta utilization patterns confirms its good pregnancy rates while minimizing OHSS risk during first ovarian stimulation cycle.

Oocyte Quality Assessment in Breast Cancer: Implications for Fertility Preservation.

BACKGROUND: The aim of this study was to evaluate the effects of breast cancer on the ovarian response and on oocyte quality following controlled ovarian hyperstimulation (COH). METHODS: This retrospective case-control study evaluated the effects of breast cancer on the ovarian response and on the oocyte quality. Oncological patients with breast cancer undergoing controlled ovarian stimulation cycles for fertility preservation, and age- and date-matched controls undergoing COH for in vitro fertilization (IVF) for male or tubal factor infertility were included in the study. Two hundred and ninety-four women were enrolled: 105 affected by breast cancer and 189 healthy women in the control group. Both groups were comparable in terms of age, BMI, and AMH value. Maximal estradiol levels on the triggering day, duration of stimulation, total amount of gonadotropins administered, number of oocytes retrieved, rate of metaphase 2 oocyte production, and numbers of immature and dysmorphic oocytes were analyzed. RESULTS: Considering factors influencing the oocyte quality, such as age, BMI, AMH, duration of stimulation, E2 level on the triggering day, total FSH cumulative dose, stage, histotype, BRCA status, and hormone receptors, the univariate and multivariate analyses identified breast cancer as a risk factor for the presence of dysmorphic oocytes. CONCLUSIONS: The diagnosis of breast cancer does not seem to be associated with the impairment of the ovarian reserve, but is linked to a worsening oocyte quality.

Female fertility preservation: Impact of cancer on ovarian function and oocyte quality.

OBJECTIVE: To evaluate the influence of cancer on ovarian response and oocyte quality in controlled ovarian hyperstimulation (COH). METHODS: This prospective study conducted at the Physiopathology of Reproduction and Andrology Unit of Sandro Pertini Hospital enrolled 82 cancer patients undergoing controlled ovarian stimulation (COH) cycles for fertility preservation, and age- and date-matched controls undergoing COH for in vitro fertilization for male-factor infertility from June 2016 to November 2019. The interventions performed were COH, oocyte retrieval, and quality evaluation. Main outcome measures were maximal estradiol levels on the day of human chorionic gonadotropin administration, duration of stimulation, total amount of gonadotropins administered, number of oocytes retrieved, and rates of metaphase 2 oocytes and abnormal oocytes. All data were analyzed using the Statistical Package for the Social Sciences (IBM Corp., Armonk, NY, USA) 22.0. RESULTS: Intergroup comparisons (82 cancer patients and 180 patients in control group) showed a significant difference in ovarian response, especially for a significant higher number of abnormal oocytes in cancer patients (P < 0.0001). Regression analysis to assess the influence of the neoplastic process, regardless of the type, on ovarian response showed an effect on the main outcome measured due to cancer itself. CONCLUSION: Cancer influences the ovarian response, particularly the oocyte quality, during COH performed for fertility preservation.

Fertility counseling in women with hereditary cancer syndromes.

Hereditary cancer syndromes are a heterogeneous group of genetic conditions that are associated with an increased risk of developing cancer during lifespan. In affected women, parenthood may be accompanied by concerns for the offspring, considering the common autosomal dominant inheritance. Moreover, fertility preservation to prevent the detrimental effects of cancer treatments differs compared to other clinical contexts. The necessity to preserve gametes is indeed predictable and expected to be common. For these reasons, we advocate a personalized and early fertility counseling. Carriers should be aware of the risk of transmission. The possibility to perform elective oocytes cryopreservation, either before (previvors) or after (survivors) cancer diagnosis should be discussed. Finally, they should be informed about the options of preimplantation genetic test (PGT) and oocytes donation. In conclusion, physicians engaged in oncofertility should personalize the counseling for women with hereditary cancer syndromes, being aware of their peculiar needs.