The Promise and Pitfalls of AI-Generated Anatomical Images: Evaluating Midjourney for Aesthetic Surgery Applications.

BACKGROUNDS: The rapid advancement of generative artificial intelligence (AI) systems, such as Midjourney, has paved the way for their use in medical training, producing computer-generated images. However, despite clear disclosures stating that these images are not intended for medical consultations, their accuracy and realism are yet to be thoroughly examined. METHODS: A series of requests were addressed to the Midjourney AI tool, a renowned generative artificial intelligence application, with a focus on depicting appropriate systemic anatomy and representing aesthetic surgery operations. Subsequently, a blinded panel of four experts, with years of experience in anatomy and aesthetic surgery, assessed the images based on three parameters: accuracy, anatomical correctness, and visual impact. Each parameter was scored on a scale of 1-5. RESULTS: All of images produced by Midjourney exhibited significant inaccuracies and lacked correct anatomical representation. While they displayed high visual impact, their unsuitability for medical training and scientific publications became evident. CONCLUSIONS: The implications of these findings are multifaceted. Primarily, the images' inaccuracies render them ineffective for training, leading to potential misconceptions. Additionally, their lack of anatomical correctness limits their applicability in scientific articles. Although the study focuses on a single AI tool, it underscores the need for collaboration between AI developers and medical professionals. The potential integration of accurate medical databases could refine the precision of such AI tools in the future. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The relationship between CYP19A1 gene expression in luteinized granulosa cells and follicular estradiol output in women with endometriosis.

Endometriosis was claimed to negatively affect the intrafollicular environment, hindering oocyte competence. Previous studies evaluated expression levels of cytochrome P450 aromatase (CYP19A) in granulosa and cumulus oophorus cells collected from endometriosis women, but results are controversial. To further investigate the intrafollicular environment whose alteration may potentially disturb ovarian steroidogenesis in endometriosis, gene expression of CYP19A and of its upstream enzymes, StAR and 3ßHSD was assessed in luteinized granulosa cells isolated from follicular fluids (FF) collected during Assisted Reproduction Technology (ART) procedures in women with stage III-IV disease and from subjects without the condition. In a subgroup of patients, cumulus oophorus cells (COCs) were also assessed for CYP19A, StAR and 3ßHSD gene expression. No difference in mRNA expression of CYP19A1, StAR and 3ßHSD in both granulosa cells and COCs was observed between the two groups of patients. No significant difference was also found between estradiol FF levels detected in endometriosis patients (median=873, IQR=522-1221 ng/ml)) and control patients (median=878, IQR=609-1137 ng/ml). To gain more insight into the intrafollicular regulation of CYP19A in patients with endometriosis, associations between expression of the analyzed genes, systemic and follicular 17ß-estradiol levels and ART outcomes were assessed. While in the control group, levels of CYP19A1, StAR and 3ßHSD transcripts significantly correlated with follicular estradiol levels (adjusted R² of 0.60), no significant association was detected in affected women (adjusted R² of 0.23). After stratification of the populations based on the presence of the disease, CYP19A1 expression was shown to correlate with the number of oocytes retrieved [ß:- 1.214;95%CI: - 2.085 - (-0.343); p = 0.007] in the control group while this association was not present in patients with endometriosis [ß:- 0.003; 95%CI:- 0.468-0.461; p = 0.988)]. These results do not support data from the literature indicating a reduced aromatase expression in granulosa cells of affected women, but they highlight a potential subtle mechanism affecting the ovulation process in these women.

The Task Matters: A Comprehensive Review and Proposed Literature Score of the Effects of Chemical and Physical Parameters on Embryo Developmental Competence.

To explore the effects of chemical and physical parameters on embryo developmental competence, we conducted a systematic search on PubMed for peer-reviewed original papers using specific keywords and medical subject heading terms. Studies of interest were selected from an initial cohort of 4141 potentially relevant records retrieved. The most relevant publications were critically evaluated to identify the effect of these parameters on embryo development. Moreover, we generated a literature score (LS) using the following procedure: (i) the number of studies favoring a reference group was expressed as a fraction of all analyzed papers; (ii) the obtained fraction was multiplied by 10 and converted into a decimal number. We identified and discussed six parameters (oxygen, temperature, humidity, oil overlay, light, pH). Moreover, we generated a LS according to five different comparisons (37 °C vs. <37 °C; 5% vs. 20% oxygen; 5-2% vs. 5% oxygen; humidity conditions vs. dry conditions; light exposure vs. reduced/protected light exposure). Only two comparisons (37 °C vs. <37 °C and 5% vs. 20% oxygen) yielded a medium-high LS (8.3 and 7, respectively), suggesting a prevalence of studies in favor of the reference group (37 °C and 5% oxygen). In summary, this review and LS methodology offer semi-quantitative information on studies investigating the effects of chemical and physical parameters on embryo developmental competence.

Low Birth Weight is Associated with Sperm DNA Fragmentation and Assisted Reproductive Technology Outcomes in Primary Infertile Men: Results of a Cross-Sectional Study.

PURPOSE: To assess the relationship between clinical and semen characteristics and assisted reproductive technology (ART) outcomes with different birth weight (BW) categories in a cohort of infertile men. MATERIALS AND METHODS: Data from 1,063 infertile men were analyzed. Patients with BW ≤2,500, 2,500-4,000, and ≥4,000 g were considered as having low BW (LBW), normal BW (NBW), and high BW (HBW), respectively. Testicular volume (TV) was assessed with a Prader orchidometer. Serum hormones were measured in all cases. Semen analyses were categorized based on 2021 World Health Organization reference criteria. Sperm DNA fragmentation (SDF) was tested in every patient and considered pathological for SDF >30%. ART outcomes were available for 282 (26.5%) patients. Descriptive statistics and logistic regression analyses detailed the association between semen parameters and clinical characteristics and the defined BW categories. RESULTS: Of all, LBW, NBW, and HBW categories were found in 79 (7.5%), 807 (76.0%), and 177 (16.5%) men, respectively. LBW men had smaller TV, presented higher follicle-stimulating hormone (FSH) but lower total testosterone levels compared to other groups (all p<0.01). Sperm progressive motility (p=0.01) and normal morphology (p<0.01) were lower and SDF values were higher (all p<0.01) in LBW compared to other groups. ART pregnancy outcomes were lower in LBW compared to both NBW and HBW categories (26.1% vs. 34.5% vs. 34.5%, p=0.01). At multivariable logistic regression analysis, LBW was associated with SDF >30% (odd ratio [OR] 3.7; p<0.001), after accounting for age, Charlson Comorbidity Index (CCI), FSH, and TV. Similarly, LBW (OR 2.2; p<0.001), SDF >30% (OR 2.9; p<0.001) and partner's age (OR 1.3; p=0.001) were associated with negative ART outcomes, after accounting for the same predictors. CONCLUSIONS: LBW was associated with impaired clinical and semen characteristics in infertile men compared to both NBW and HBW. SDF and ART outcomes were significantly worse in the LBW group.

Progesterone levels during ovarian stimulation in segmented ART cycles inversely correlate with normalized birthweight of neonates conceived through subsequent frozen-thawed embryo transfer.

PURPOSE: To evaluate the association between serum progesterone (P) at the day of ovulation trigger and neonatal birthweight in singletons born after frozen-thawed embryo transfer in segmented ART cycles. METHODS: A retrospective multicenter cohort study involving data from patients who achieved uncomplicated pregnancy and term delivery of ART-conceived singleton babies following a segmented GnRH antagonist cycle. The main outcome was birthweight's z-score of the neonate. Univariate and multivariate linear logistic regression analyses were made to investigate the relation of z-score with variables inherent to the patient and to the ovarian stimulation. The variable P per oocyte was created by dividing the value of progesterone at ovulation trigger by the number of oocytes retrieved at oocyte retrieval. RESULTS: A total of 368 patients were included in the analysis. At univariate linear regression, the birthweight z-score of the neonate appeared to be inversely related to both P levels at the ovulation trigger (- 0.101, p = 0.015) and P levels per oocyte at trigger (- 1.417, p = 0.001), while it was directly related to the height of the mother (0.026, p = 0.002) and to the number of previous live births (0.291, p = 0.016). In multivariate analysis, both serum P (- 0.1; p = 0.015) and P per oocyte (- 1.347, p = 0.002) maintained the significant inverse association with birthweight z-score after adjusting for height and parity. CONCLUSIONS: Serum progesterone level on the day of ovulation trigger inversely correlates with normalized birthweight of neonates in segmented GnRH antagonist ART cycles.

Fertility Preservation as an Option for Women with Genetic Disorders: Insights from a SWOT Analysis on Elective Oocyte Freezing and Preimplantation Genetic Testing.

This paper uses a SWOT (strengths, weaknesses, opportunities, and threats) analysis to overview the option of fertility preservation in women with genetic diseases, who would later use preimplantation genetic testing for monogenic disorders, in order to not transmit their condition. Strengths associated with elective oocyte freezing are ethical considerations, overall maternal and fetal safety, and effectiveness, if performed at <35 years of age. Weaknesses are related to costs and rare but present (<1-3%) risks of maternal complications. Counselling on fertility management aimed at preventing infertility offers a valuable opportunity, the same as it has been in oncological patients' care. The potentially high percentage of women with genetic conditions who would return to use their frozen oocytes also represents an opportunity together with the minimization of the need for egg donation, which has higher obstetrical risks compared to the use of autologous oocytes. Finally, a threat is represented by the potential psychological distress to young women who could never attempt to become pregnant through preimplantation genetic testing, or do it before any decline in their fertility. Potential unknown future long-term health risks for children conceived after egg vitrification/thawing are also a threat, but current knowledge is reassuring. Altogether, early counselling on the option of fertility preservation should thus be incorporated into standard care of all patients with any genetic condition.

Anti-Müllerian hormone predicts positive sperm retrieval in men with idiopathic non-obstructive azoospermia-findings from a multi-centric cross-sectional study.

STUDY QUESTION: Is it possible to identify a reliable marker of successful sperm retrieval (+SR) in men with idiopathic non-obstructive azoospermia (iNOA) undergoing microdissection testicular sperm extraction (mTESE)? SUMMARY ANSWER: A higher likelihood of +SR during mTESE is observed in men with iNOA and lower preoperative serum anti-Müllerian hormone (AMH) levels, with good predictive accuracy achieved using an AMH threshold of <4 ng/ml. WHAT IS KNOWN ALREADY: AMH has been previously linked to +SR in men with iNOA undergoing mTESE prior to ART. STUDY DESIGN, SIZE, DURATION: A multi-centre cross-sectional study was carried out with a cohort of 117 men with iNOA undergoing mTESE at three tertiary-referral centres. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data from 117 consecutive white-European men with iNOA presenting for primary couple's infertility associated with a pure male factor at three centres were analysed. Descriptive statistics was applied to compare patients with negative (-SR) versus +SR at mTESE. Multivariate logistic regression models were fitted to predict +SR at mTESE, after adjusting for possible confounders. Diagnostic accuracy of the factors associated with +SR was assessed. Decision curve analyses were used to display the clinical benefit. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, 60 (51.3%) men had an -SR and 57 (48.7%) had a +SR at mTESE. Patients with +SR had lower levels of baseline AMH (P = 0.005) and higher levels of estradiol (E2) (P = 0.01). At multivariate logistic regression analysis, lower levels of AMH (odds ratio: 0.79; 95% CI: 0.64-0.93, P = 0.03) were associated with +SR at mTESE, after adjusting for possible confounders (e.g. age, mean testicular volume, FSH, and E2). A threshold of AMH <4 ng/ml achieved the highest accuracy for +SR at mTESE, with an AUC of 70.3% (95% CI: 59.8-80.7). Decision curve analysis displayed the net clinical benefit of using an AMH <4 ng/ml threshold. LIMITATIONS, REASONS FOR CAUTION: There is a need for external validation in even larger cohorts, across different centres and ethnicities. Systematic reviews and meta-analysis to provide high level of evidence are lacking in the context of AMH and SR rates in men with iNOA. WIDER IMPLICATIONS OF THE FINDINGS: Current findings suggest that slightly more than one in two men with iNOA had -SR at mTESE. Overall, men with iNOA with lower levels of AMH had a significantly higher percentage of successful SR at surgery. A threshold of <4 ng/ml for circulating AMH ensured satisfactory sensitivity, specificity, and positive predictive values in the context of +SR at mTESE. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by voluntary donations from the Urological Research Institute (URI). All authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Response to Controlled Ovarian Stimulation Is Not Impaired in Young Patients with a Sarcoma: Results from a Monocentric Case-Control Study.

Sarcomas are relatively common in the young and their treatment can impair fertility. Fertility preservation can be achieved via the cryopreservation of gametes after controlled ovarian stimulation before cancer treatment. A reduced response to hormonal stimulation in patients suffering from certain types of malignancy is reported. The purpose of this study was to assess the performance of oocyte cryopreservation in patients with sarcoma by comparing their outcomes with those of a population without cancer. Patients were matched by age with control women undergoing hormonal stimulation for isolated male factor infertility. The population included 84 women with a sarcoma and 355 controls. In the final analysis, 37 patients with sarcoma were matched in a 1:3 ratio with 109 healthy controls. Patients with sarcoma were generally younger and were stimulated with lower FSH doses. They did not perform worse than controls during stimulation, with an average retrieval of 10.6 oocytes vs. 8.1 in the controls. Linear regression on the number of retrieved mature oocytes confirmed that patients with sarcoma performed comparably to controls. In conclusion, patients with sarcoma can expect retrieval outcomes comparable to those of patients without cancer.

Concomitant Autoimmunity in Endometriosis Impairs Endometrium-Embryo Crosstalk at the Implantation Site: A Multicenter Case-Control Study.

Endometriosis and autoimmune diseases share a hyper-inflammatory state that might negatively impact the embryo-endometrium crosstalk. Inflammatory and immune deregulatory mechanisms have been shown to impair both endometrial receptivity and embryo competence at the implantation site. The aim of this study was to investigate the potential additional impact of co-existing autoimmunity in women affected by endometriosis on the early stages of reproduction. This was a retrospective, multicenter case-control study enrolling N = 600 women with endometriosis who underwent in vitro fertilization-embryo transfer cycles between 2007 and 2021. Cases were women with endometriosis and concomitant autoimmunity matched based on age and body mass index to controls with endometriosis only in a 1:3 ratio. The primary outcome was the cumulative clinical pregnancy rate (cCPR). The study found significantly lower cleavage (p = 0.042) and implantation (p = 0.029) rates among cases. Autoimmunity (p = 0.018), age (p = 0.007), and expected poor response (p = 0.014) were significant negative predictors of cCPR, with an adjusted odds ratio of 0.54 (95% CI, 0.33-0.90) for autoimmunity. These results suggest that the presence of concomitant autoimmunity in endometriosis has a significant additive negative impact on embryo implantation. This effect might be due to several immunological and inflammatory mechanisms that interfere with both endometrial receptivity and embryo development and deserves further consideration.

"Better late than never but never late is better", especially in young women. A multicenter Italian study on diagnostic delay for symptomatic endometriosis.

PURPOSE: The aim of the study was to assess the length of diagnostic delay of symptomatic endometriosis in Italy and analyse the presence of correlations between the socio-demographic status of patients and the clinical characteristics/type of diagnosis. MATERIALS AND METHODS: This multicenter cross-sectional questionnaire-based study was conducted in 10 tertiary Italian referral centres for diagnosis and treatment endometriosis. A total of 689 respondents with histologically proven endometriosis and onset of the disease with pain symptoms completed an on-line self-reported questionnaire written in their own language (World Endometriosis Research Foundation-Endometriosis Phenome and Biobanking Harmonisation Project-Endometriosis Patient Questionnaire-Minimum) evaluating endometriosis related symptoms, family history of endometriosis and chronic pelvic pain, demographic data, as well as medical, reproductive, and obstetric history. RESULTS: The mean diagnostic delay found was of 11.4 years. The mean time (14.8 years) from symptoms onset to diagnosis was significantly longer among patients aged 9-19 vs patients aged 20-30 (mean 6.9 years, p < 0.001) and patients aged 31-45 (mean 2.9, p < 0.001). No significant association were found between a delayed diagnosis and any of the clinically relevant factors such as the number or severity of the reported symptoms, familiarity, hormonal therapy intake or methodology of diagnosis. CONCLUSIONS: The mean diagnostic delay of endometriosis in Italy is about 11 years. The delay can be up to 4 years longer in patients with pain symptoms onset under 20 years. Educating clinicians and patients on pathologic nature of endometriosis related pelvic pain is advisable to reduce waiting time to diagnosis, especially for young women.

Delayed blastocyst development is influenced by the level of progesterone on the day of trigger.

PURPOSE: To evaluate the association between progesterone (P) level on the day of trigger and time to blastulation in IVF cycles. METHODS: This was a retrospective cohort study with autologous IVF cycles performed at our Institution from January 2019 to December 2021. A total of 1109 IVF cycles were included. The primary outcome was to compare time to blastulation in terms of percentage of expanded (grade 3) blastocysts on day 5 according to progesterone level at trigger. RESULTS: A total of 3517 blastocysts were analyzed. After dividing progesterone level in quartiles (Q1, P < 0.50 ng/ml; Q2 0.50 ng/ml ≤ P ≤ 0.78 ng/ml; Q3, 0.79 ng/ml ≤ P ≤ 1.15 ng/ml; Q4, P > 1.15 ng/ml), we observed a delay in blastocyst development according to the increasing level of progesterone at trigger (analysis by rank, P-value = 0.01). After adjusting for confounding factors at the multivariate analysis, the percentage of day 5 blastocysts was reduced for Q3 (- 13.8%, 95% CI from - 20.5 to - 7.0%, p < 0.001) and Q4 (- 7.7%, 95% CI from - 15.5 to 0.0%, p = 0.05) compared to Q1 (reference). CONCLUSIONS: Progesterone levels on day of trigger correlate to the percentage of expanded (grade 3) blastocysts on day 5 and a delayed blastocyst development day 5 is expected for high progesterone levels.

A prospective, observational study of chemotherapy-induced ovarian damage on follicular reserve and maturation.

BACKGROUND: Chemotherapy negatively affects gonadal function, often resulting in premature ovarian failure (POF) due to ovarian reserve depletion. Mechanisms of gonadotoxicity, such as primordial follicle overactivation and "burnout", remain to be established. Ovarian tissue cryopreservation (OTC) before treatment plays an important role in safeguarding fertility. METHODS: This is a prospective observational study that aims to evaluate the feasibility of OTC after chemotherapeutic treatment initiation. Patients were divided into 2 groups depending on whether they received chemotherapy before the harvesting procedure (Group 1) or not (Group 2). The main outcomes of this study are serum anti-Mullerian hormone (AMH) levels and histological follicular counts on ovarian tissue biopsies. RESULTS: Between 2012 and 2020, 79 patients underwent OTC at our Hospital. Follicular counts from the ovarian biopsies of 30 post-pubertal patients and respective serum AMH levels were included in the analysis. AMH levels did not significantly differ between the 2 groups (P = 0.70) as well as the number of primordial follicles (P = 0.73). Ovarian biopsies of patients from Group 1 showed a higher number of primary follicles (P = 0.04) and atretic follicles (P = 0.05) with respect to Group 2. CONCLUSIONS: In conclusion, OTC appears to be feasible even after the start of chemotherapeutic treatment, since in treated patients, the main ovarian reserve indicators (number of primordial follicles and serum AMH levels) were not significantly reduced compared to untreated patients. The "burnout" theory of chemotherapeutic damage to the ovary seems to be supported by the higher number of primary follicles found in the ovaries of patients who received chemotherapy before OTC.

Ovarian failure risk in post-pubertal patients with cancer: a prognostic model.

Aim: To develop a predictive model for ovarian failure (OF) after chemotherapy in young post-pubertal women with cancer. Methods: Retrospective, monocentric cohort study including 348 patients referring to the Oncofertility Unit of San Raffaele Hospital (Milan, Italy) from August 2011 to January 2020. A predictive model was constructed by multivariate logistic regression and receiver operating characteristic analysis. Results: Data about menstrual function resumption were available for 184 patients. The best predictive model for OF was identified by the combination of age; number of chemotherapy lines; vincristine, adriamycin, ifosphamide/adriamycin, ifosphamide; capecitabine; adriamycin, bleomycine, vinblastine, doxorubicin (area under the curve = 0.906; CI 95% 0.858-0.954; p = 0.0001). Conclusions: The model predicts the probability of loss of ovarian function at cancer diagnosis and with every change of treatment.

Chemotherapy can reduce fertility in young women surviving cancer. The effects of chemotherapy on ovarian function range from no damage to several degrees of reduced fertility. In some cases, premature menopause can occur. This variability depends on many different individual and treatment-related factors. In this study, we analyzed the outcomes in terms of menses regularity and fertility of 348 oncological patients receiving counseling on fertility at our unit from August 2011 to January 2020. We developed a predictive model to estimate the risk of premature menopause of each patient, to be used at diagnosis and every time a new treatment must be started. This model includes a combination of patient's age, number of lines of chemotherapeutic treatment, and three chemotherapy schedules commonly used in young patients with cancer. It allows an improved counseling on fertility, and it can aid decision making regarding fertility preservation strategies for each patient.

Triglycerides/Glucose Index Is Associated with Sperm Parameters and Sperm DNA Fragmentation in Primary Infertile Men: A Cross-Sectional Study.

STUDY QUESTION: we aimed to investigate the relationship between the tyg index and both semen and hormonal characteristics in a cohort of primary infertile men. Summary answer: almost one in two primary infertile men presented with a triglycerides/glucose index (tyg) suggestive of insulin resistance (ir). overall, patients with tyg suggestive of ir showed worse clinical, hormonal, and semen parameters. What is already known: male factor infertility (MFI) is often associated with metabolic disorders such as diabetes mellitus and metabolic syndrome, where insulin resistance (IR) plays a relevant pathological role. Recently, TyG has been suggested as a user-friendly IR marker. STUDY DESIGN: serum hormones and the sperm DNA fragmentation index (SDF) were measured in every patient. The semen analysis was based on 2010 WHO reference criteria. Glucose and insulin levels were measured for every man after a 12-h overnight fast, and the homeostatic model assessment index (HOMA-IR) was then calculated and categorized using a 2.6 threshold. Similarly, fasting glucose and triglycerides levels were measured and the TyG index was calculated and categorized using an 8.1 threshold. Descriptive statistics and logistic regression models tested the association between the TyG and semen and hormonal characteristics. PARTICIPANTS: complete demographic, clinical, and laboratory data from 726 consecutive white European primary infertile men were considered for this analysis. Main results and the role of chance: the median (IQR) age was 39 (35-43) years. A TyG and HOMA suggestive for IR was found in 339 (46.6%) and 154 (21.2%) men, respectively. During the Spearman's test, the TyG index was highly correlated with HOMA-IR (rho = 0.46, p < 0.001). Compared to men with a normal TyG, men with TyG > 8.1 were older, had greater BMI and CCI scores, and lower total testosterone and sperm concentration, but higher DFI, and presented a greater proportion of NOA (all p < 0.01). The multivariable logistic regression analysis showed that men with TyG > 8.1 were at higher risk of SDF > 30 (OR 1.92 (CI: 1.2-2.9)) and NOA (OR 1.78 (CI: 1.1-2.8)). Wider implications of the findings: the Tyng index may act as a reliable marker of IR in the clinical work-up of primary infertile men in real-life settings.

COVID-19 Vaccination Does Not Affect Reproductive Health Parameters in Men.

With the implementation of COVID-19 vaccine up-take, doubts regarding the impact of immunization on future fertility have begun to emerge. We have examined vaccine safety on male reproductive health. We set up a multicentre (three infertility centers), retrospective study in order to assess semen parameters and fertilization rate of one hundred-six men in a pairwise comparison between the first and second assisted reproduction technology (ART) attempt, performed respectively before and after COVID-19 vaccination. Median time (range) between the first vaccine dose and the second ART cycle was 75 days (39-112). Semen parameters did not change before and after the exposure. Fertilization rate was also similar before and after vaccination. Twenty-five patients (24%) were oligozoospermic before the vaccination while 26 (25%) after the exposure (P = 0.87). Severe asthenozoospermia were present in 11 patients before as well as after the exposure. No difference was observed even after considering different types of vaccines (mRNA or viral vector). COVID-19 vaccination did not affect sperm quality and fertilization capacity of men undergoing ART treatments and should be considered safe for men's reproductive health.

The effect of vitrified-warmed blastocyst transfer on postnatal growth: a 1-year follow-up questionnaire study.

RESEARCH QUESTION: Is postnatal growth of singletons aged 12 months born after vitrified-warmed blastocyst transfer (frozen embryo transfer [FET]) different from children born after fresh blastocyst transfer? DESIGN: A retrospective cohort study conducted at a single university-affiliated obstetrics and fertility centre between 2014 and 2016. Women who underwent fresh transfer or FET at blastocyst stage and obtained a singleton live birth were included. Propensity score inverse probability weighting was used to balance baseline maternal characteristics between fresh and FET cycles. RESULTS: Of the 382 women with singleton live births, 124 underwent a fresh blastocyst transfer and 258 underwent a FET. Significantly higher birth weight and length z-scores were observed after FET (P = 0.01 and P = 0.002, respectively) compared with the fresh transfer group. At 12 months of age, the fresh and FET groups showed no significant effect on the weight z-score, but the FET was associated with a higher height z-score (P = 0.001) compared with fresh blastocyst transfer. The comparison between males and females from the same study group showed higher birth weight z-score for males in the FET group (P < 0.001). During the first 12 months, however, males in the FET group showed a slower growth trajectory in terms of weight (P = 0.007). CONCLUSIONS: At 12 months of postnatal life, an increased height and sex-dependent differences in growth trajectories were observed in singletons born after FET compared with those born after fresh embryo transfer.

Clinical Outcomes Deriving from Transfer of Blastocysts Developed in Day 7: a Systematic Review and Meta-Analysis of Frozen-Thawed IVF Cycles.

This meta-analysis aimed to assess the reproductive competence of blastocysts developed on day 7 compared with blastocysts developed on day 5/6. A systematic search was carried out to select relevant studies published before January 2020. Ten retrospective observational cohort studies were included. The primary outcome was the clinical pregnancy rate (CPR). Secondary outcomes were live birth rate (LBR), euploid rate, and survival rates after thawing. Frozen-thawed day 7 blastocyst transfer was associated with a significant reduction in CPR compared to day 5/6 (OR 0.36 95% CI 0.21 to 0.62, p = 0.0002, I2 = 71% and OR 0.43, 95% CI 0.32 to 0.58, p < 0.0001, I2 = 17% respectively). A significantly lower proportion of LBR was found comparing blastocysts transfers in day 7 to those in day 5/6 (OR 0.21, 95% CI 0.16-0.27, p < 0.0001, I2 = 0% and OR 0.34, 95% CI 0.26-0.45, p < 0.0001, I2 = 0% respectively). These findings were confirmed in a subgroup of Preimplantation Genetic Testing for Aneuploidies (PGT-A)-screened blastocysts. Blastocysts biopsied in day 7 was associated with a significant decrease of euploid rate compared with day 5/6 (OR 0.47, 95% CI 0.39-0.57, p < 0.0001, I2 = 69% and OR 0.68, 95% CI 0.61-0.75, p < 0.0001, I2 = 19% respectively). The survival rate after thawing was not statistically different. Sensitivity analyses were also performed. This study shows an association between delayed blastulation and a poorer prognosis in terms of euploid rate and pregnancy outcomes following frozen-thawed transfers. On the other hand, the results do not support the discharge of slow-blastulation embryos.

Levonorgestrel-releasing intrauterine system versus oral medroxyprogesterone acetate in infertile women with endometrial hyperplasia without atypia.

RESEARCH QUESTION: How does use of a levonorgestrel-releasing intrauterine system (LNG-IUS) in infertile women with endometrial hyperplasia without atypia affect endometrial hyperplasia regression and pregnancy rates compared with oral medroxyprogesterone acetate (MPA)? DESIGN: This prospective cohort study included 215 infertile women with an indication for assisted reproductive technology (ART) and a diagnosis of endometrial hyperplasia without atypia. Endometrial hyperplasia was diagnosed by hysteroscopic endometrial biopsy. At the time of first- and second-line treatment, patients were offered therapy with either oral MPA 10 mg daily or LNG-IUS. Follow-up biopsies were scheduled after 90 days' treatment. After endometrial hyperplasia regression, patients were admitted to IVF/intracytoplasmic sperm injection (ICSI) cycles. RESULTS: Baseline characteristics and confounders including age at diagnosis, body mass index and duration of infertility did not differ between LNG-IUS users and control participants and were accounted for using propensity score weighting. Endometrial hyperplasia regression rate at first follow-up was higher in the LNG-IUS group than the oral progestins group (28/28, 100% and 110/187, 58.8%; P < 0.001), while that after second-line treatment was comparable between the two groups (89/91, 97.8% and 122/124, 98.4%; P = 0.22). Clinical pregnancy rate, miscarriage rate and cumulative live birth rate following ART in patients ever receiving LNG-IUS were similar to those of patients receiving only MPA (34% versus 39.5%, 22.6% versus 34.7% and 26.4% versus 25.8%). CONCLUSION: Endometrial hyperplasia regression is greater in women receiving LNG-IUS compared with oral MPA, while live birth rates following ART are comparable between the two groups. The use of LNG-IUS does not jeopardize the chances of pregnancy in women seeking fertility treatment.

Association between short-term exposure to particulate matter air pollution and outcomes of assisted reproduction technology in Lombardy, Italy: A retrospective cohort study.

The harmful effect of polluted air on spontaneous fertility has been consistently reported. However, the specific pollutants involved in determining this effect are still to be clarified. The study of Assisted Reproductive Technology (ART) populations is particularly helpful in this context since it allows to monitor the key events of the reproductive process. We analyzed the medical records of 2122 patients who underwent fresh or frozen ART cycles during 2014-2017 in the Lombardy region, north-west Italy. Each subject was assigned the daily PM10 estimates concentration, at the municipality of residence, during the induction of multiple follicular growth. A multivariable linear regression model with a repeated-measures design was used to estimate the association between short-term exposure to PM10 and ART outcomes, A reduction in the number of retrieved oocytes in association with 10 µg/m3 increment of the pollutant estimated at 13-14 days before oocyte retrieval (Day 0) and a decrease in the percentage of metaphase II oocytes for 1-week and 2-weeks mean exposure before day 0 were observed. For cumulative pregnancies, a significant lag time change effect for PM10 exposure (Day -9-0) has been detected, by means of multivariable logistic regression models. An increase in PM10 exposure was associated with a decrease in clinical and ongoing pregnancies while a decrease in PM10 exposure was associated with a significant increase in pregnancy rates. In a population living in a highly polluted area in Italy, we added suggestive evidence of a negative association between ART outcomes and PM10 exposure after controlling for known risk factors for ART success rate.

Do stage and grade of malignancy impact fertility preservation in breast cancer patients?

INTRODUCTION: The impact of cancer on basal fertility and ovarian response to stimulation has not yet been clarified. Evidence on this topic is scarce and conflicting. Aim of this study was to assess the impact of breast cancer stage and grade on the number of retrieved mature oocytes during controlled ovarian stimulation for fertility preservation. METHODS: Retrospective cohort study evaluating data on 101 stimulation cycles of women with breast cancer undergoing oocyte cryopreservation categorized according to breast cancer stage (low-stage: I; high-stage:II-III) and grade (low-grade: G1-2; high-grade: G3) using the American Joint Committee on Cancer staging system (VIII edition). RESULTS: High-stage disease was not associated with worse oocyte retrieval outcomes (median 7 vs 7, p = 0.75). High-grade disease patients showed a significantly lower antral follicle count (AFC) compared to low-grade disease patients (10 vs 13, p = 0.03), and required higher doses of FSH (2612 IU vs 2250 IU; p = 0.03) during stimulation. Median number of vitrified oocytes was 6 in low-grade disease patients and 7 in high-grade disease patients (p = 0.35). CONCLUSIONS: Stage and grade of breast cancer do not impact the number of retrieved mature oocytes. However, higher grade of breast cancer is associated with lower AFC at baseline and need for higher doses of gonadotropin during ovarian stimulation.