The metrics maze in science: navigating academic evaluation without journalistic pressures.

In recent years a troubling trend has emerged in the medical research field, notably in reproductive medicine, manifesting an increased emphasis on quantity over quality in articles published. The pressure to collect copious publication records risks compromising meticulous expertise and impactful contributions. This tendency is exemplified by the rise of 'hyper-prolific researchers' publishing at an extraordinary rate (i.e. every 5 days), prompting a deeper analysis of the reasons underlying this behaviour. Prioritizing rapid publication over Galileo Galilei's systematic scientific principles may lead to a superficial approach driven by quantitative targets. Thus, the overreliance on metrics to facilitate academic careers has shifted the focus to numerical quantification rather than the real scientific contribution, raising concerns about the effectiveness of the evaluation systems. The Hamletian question is: are we scientist or journalist? Addressing these issues could necessitate a crucial re-evaluation of the assessment criteria, emphasizing a balance between quantity and quality to foster an academic environment that values meaningful contributions and innovation.

The use of a pill containing ethinylestradiol-norgestimate improves female sexuality despite the decrease in circulating androgens: a pilot study.

PURPOSE: To evaluate the initial impact of a combined oral contraceptive (COC) containing norgestimate (NGM) on female sexuality and on circulating androgen levels in users. MATERIALS AND METHODS: Six months modification in the McCoy Female Sexuality Questionnaire (MFSQ) and testosterone (T) and dehydroepiandrosterone sulphate (DHEAS) serum levels in women starting a monophasic pill containing ethinyl-estradiol (EE) 35 µg and NGM 0.250 mg. RESULTS: The study was completed by 36 subjects. There was a significant increase in MFSQ during treatment (p < 0.0001) (and its domains with the exclusion of vaginal lubrication domain) with concomitant decreases in T (-4.45%, p < 0.0001) and DHEAS (-19.41%, p < 0.0001) serum levels. CONCLUSIONS: Contraception with EE/NGM was associated with a short term non-deteriorating effect on sexuality despite the evident decrease in androgen levels. Female sexuality during COC use is a complex topic and is not only linked with changes in serum androgen levels.

EE/NGM treatment has a short term non-deteriorating effect on sexuality despite the evident decrease in androgen serum levels.

De novo variants and recombination at 4q35: Hints for preimplantation genetic testing in facioscapulohumeral muscular dystrophy.

Facioscapulohumeral muscular dystrophy (FSHD) has been associated with the deletion of an integral number of 3.3 kb units of the polymorphic D4Z4 repeat array at 4q35. The prenatal identification of this defect can be carried out on chorionic villi or amniocytes, whereas preimplantation genetic testing for monogenic disorders (PGT-M) requires molecular markers linked to the D4Z4 allele of reduced size. In this context the reliability of this association is crucial. To test the informativeness of the nearby polymorphic markers we investigated recombination at 4q35 using the polymorphic markers D4S1523, D4S163 and D4S139 positioned at 0.55, 0.5 and 0.21 Mb proximal to the D4Z4 array respectively. We determined the probability of recombination events to occur in the D4Z4-D4S1523 interval considering 86 subjects belonging to 12 FSHD families and found a recombination frequency of 14% between D4Z4 and D4S1523. Our study also revealed the occurrence of de novo variants and germline mosaicism. These findings highlight the recombinogenic nature of the 4q subtelomere and indicate that caution should be taken when interpreting PGT-M results. It is advisable that a woman who underwent a PGT-M cycle undertakes a prenatal DNA analysis to confirm the size of the D4Z4 alleles carried by the fetus.

Free your patients and yourself from day 2-3: start ovarian stimulation any time in freeze-all cycles.

Ovarian stimulation for assisted reproductive technology is traditionally started in the early follicular phase. The essential rationale is to allow timely follicle growth and oocyte retrieval to ensure synchronization of the in-vitro cultured embryos with the receptive period of the endometrium in a fresh transfer cycle. In addition, conventional thought suggested that follicle recruitment happened only once, around menstruation. A deeper understanding of folliculogenesis, advances in cryobiology and an increasing proportion of freeze-all cycles provide a unique opportunity here. Experience from oncofertility patients as well as infertile women and oocyte donors who underwent ovarian stimulation in different phases of the menstrual cycle, dubbed 'random start' cycles, suggests that the number of oocytes collected and their reproductive potential do not depend on the time of starting ovarian stimulation, although the duration of stimulation and gonadotrophin consumption can vary slightly. It may be time to free both patients and clinics from the obsession with starting ovarian stimulation in the early follicular phase in planned freeze-all cycles. The flexibility provided by random start cycles is one aspect of individualizing treatment to patients' needs.

New insights into the role of LH in early ovarian follicular growth: a possible tool to optimize follicular recruitment.

Evidence shows that LH participates in enhancing transition from the early stage to the antral stage of folliculogenesis. It has been demonstrated that functional LH receptors are expressed, albeit at a very low level and even in smaller follicles, during the phase that was traditionally considered to be gonadotrophin independent, suggesting a role for LH in accelerating the rate of progression of non-growing and primary follicles to the preantral/antral stage. Hypogonadotropic hypogonadism, together with other clinical conditions of pituitary suppression, has been associated with reduced functional ovarian reserve. The reduction in LH serum concentration is associated with a low concentration of anti-Müllerian hormone. This is the case in hypothalamic amenorrhoea, pregnancy, long-term GnRH-analogue therapy and hormonal contraception. The effect seems to be reversible, such that after pregnancy and after discontinuation of drugs, the functional ovarian reserve returns to the baseline level. Evidence suggests that women with similar primordial follicle reserves could present with different numbers of antral follicles, and that gonadotrophins may play a fundamental role in permitting a normal rate of progression of follicles through non-cyclic folliculogenesis. The precise role of gonadotrophins in early folliculogenesis, as well as their use to modify the functional ovarian reserve, must be investigated.

Anti-Müllerian Hormone promotes human osteoblast differentiation and calcification by modulating osteogenic gene expression.

OBJECTIVE: To investigate whether the Anti-Müllerian Hormone (AMH), an ovarian hormone belonging to the Transforming Growth Factor ß superfamily, may represent a possible candidate for use as a bone anabolic factor. METHODS: We performed in vitro studies on Human Osteoblasts (HOb) to evaluate the expression and the functionality of AMHRII, the AMH receptor type-2, and investigate the effects of exogenous AMH exposure on osteogenic gene expression and osteoblast functions. RESULTS: We reported the first evidence for the expression and functionality of AMHRII in HOb cells, thus suggesting that osteoblasts may represent a specific target for exogenous AMH treatment. Furthermore, the exposure to AMH exerted a stimulatory effect on HOb cells leading to the activation of osteogenic genes, including the upregulation of osteoblastic transcription factors such as RUNX and OSX, along with increased deposition of mineralized nodules. CONCLUSION: Our findings proved interesting clues on the stimulatory effects of AMH on mature osteoblasts expressing its specific receptor, AMHRII. This study may therefore have translation value in opening the perspective that AMH may be an effective candidate to counteract the bone loss in osteoporotic patients by selectively targeting osteoblast with minimal off-target effect.

Evidence for the expression of vasorin in the human female reproductive tissues.

Objective: To investigate the expression and localization of Vasorin (Vasn) in human female reproductive system. Methods: The presence of Vasorin was evaluated by RT-PCR and immunoblotting analyses in patient-derived endometrial, myometrial and granulosa cells (GCs) primary cultures. Immunostaining analyses were performed to detect Vasn localization in primary cultures and in ovarian and uterine tissues. Results: Vasn mRNA was detected in patient-derived endometrial, myometrial and GCs primary cultures without significant differences at the transcript level. Otherwise, immunoblotting analysis showed that Vasn protein levels were significantly higher in GCs than proliferative endometrial stromal cells (ESCs) and myometrial cells. Immunohistochemistry performed in ovarian tissues revealed that Vasn was expressed in the GCs of ovarian follicles at different stages of development with a higher immunostaining signal in mature ovarian follicles such as the antral follicle or on the surface of cumulus oophorus cells than in early-stage follicles. The immunostaining of uterine tissues showed that Vasn was expressed in the proliferative stroma endometrium while it was significantly less expressed in the secretory endometrium. Conversely, no protein immunoreactivity was revealed in health myometrial tissue. Conclusions: Our results revealed the presence of Vasn in the ovary and the endometrium. The pattern of Vasn expression and distribution suggests that this protein may have a role in the regulation of processes such as folliculogenesis, oocyte maturation, and endometrial proliferation.

Oral hormonal therapy as treatment option for abnormal uterine bleeding.

BACKGROUND: abnormal uterine bleeding is a very frequent reason for referral to gynaecologists and can deeply influence the quality of life. Once organic causes requiring surgical treatment are ruled out, clinicians should be able to manage these patients conservatively in the most effective way. MATERIALS AND METHODS: a search in PubMed/MEDLINE database was conducted in order to find relevant and recent meaningful sources for this narrative review. RESULTS: LNG-IUS 52 mg is the first-line treatment for non-organic causes. Nevertheless, it could be contraindicated or declined by the patient. Combined oral contraceptives (COC) and progestin-only pills inhibit the hypothalamic-pituitary-ovarian axis, preventing ovulation, and induce endometrial atrophy. Consequently, they are effective in treating AUB. Moreover, brand new pills containing a combination of oestrogens, progestins and GnRH antagonists are now available for the management of AUB related to uterine fibroids. CONCLUSIONS: In daily clinical practice, oral hormonal therapies are convenient and reversible tools to manage AUB when LNG-IUS 52 mg is contraindicated or turn down by the patient. Many oral hormonal therapies are prescribed to treat AUB, but only a few have been approved with this specific indication, therefore further large well-designed studies are necessary in order to compare the efficacy of different pills for treating AUB.

Even though LNG-IUS 52 mg is the first-line treatment for abnormal uterine bleeding, oral hormonal therapies should be effectively managed by gynaecologists in case of contraindications or patient's decline. Contraceptive pills are practical, but further studies are necessary to compare their efficacy and to approve them with the specific AUB indication.

Extended LH administration as a strategy to increase the pool of recruitable antral follicles in hypothalamic amenorrhea: evidence from a case series.

New evidence is indicating a growing role of LH in promoting ovarian follicular growth and maturation, even at the early stages. LH seems to enhance the transition of follicles to the antral stage hence leading to an increase in the so-called functional ovarian reserve (recruitable antral follicles). Hypogonadotropic hypogonadism is characterized by low, and sometimes undetectable, serum LH and FSH levels, which may indeed explain the low anti-Müllerian hormone (AMH) levels and antral follicle count (AFC) found in patients affected by this condition. We report here the cases of two young women affected by hypothalamic amenorrhea (HA) that presented for fertility treatment with very low functional ovarian reserve. The two patients were treated with exogenous LH for 1 and 2 months (extended LH administration: ELHA) at the dose of 187.5 IU LH every day and 150 IU LH every other day, respectively. In both the cases there was an increase in serum AMH levels and in the AFC. In one patient, the AMH and AFC increased from a baseline 1.3 ng/ml and 8 to 2.3 ng/ml and 14 at end of treatment, respectively. In the second case, serum AMH and AFC increased from 0.4 ng/ml and 6 to 1.6 ng/ml and 13, respectively. One patient underwent ovarian stimulation before and after ELHA, showing an increase in the number of mature oocytes recruited (3 versus 8 metaphase II (MII) oocytes before and after, respectively). The second patient underwent an IVF cycle after ELHA resulting in the retrieval of six MII oocytes and an ongoing pregnancy following transfer of a single blastocyst. Women with HA are characterized by chronic, low levels of gonadotrophins, which may impact not only on the cyclic recruitment of follicles but also the progression of small growing follicles through the first stages of folliculogenesis. Some women with HA may in fact show very low serum AMH and AFC. Our case series shows that the administration of LH at a dose of at least 150-187.5 IU every day or every other day may contribute to a clinically evident increase in the functional ovarian reserve (AFC), and probably accounts for a positive effect of LH on the progression of follicles throughout the early stages of folliculogenesis.

The number and rate of euploid blastocysts in women undergoing IVF/ICSI cycles are strongly dependent on ovarian reserve and female age.

STUDY QUESTION: Can the possibility of having at least one euploid blastocyst for embryo transfer and the total number of euploid blastocysts be predicted for couples before they enter the IVF programme? SUMMARY ANSWER: Ovarian reserve and female age are the most important predictors of having at least one euploid blastocyst and the total number of euploid blastocysts. WHAT IS KNOWN ALREADY: The blastocyst euploidy rate among women undergoing ART has already been shown to significantly decrease with increasing female age, and the total number of euploid embryos is dependent on the blastocyst cohort size. However, the vast majority of published studies are based on retrospective analysis of data. STUDY DESIGN, SIZE, DURATION: This prospective analysis included 847 consecutively enrolled couples approaching their first preimplantation genetic testing for aneuploidies (PGT-A) cycle between 2017 and 2020. Only couples for whom ejaculated sperm was available and women with a BMI of <35 kg/m2 were included in the study. Only the first cycle was included for each patient. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was conducted at an IVF centre where, for all patients, the planned treatment was to obtain embryos at the blastocyst stage for the PGT-A programme. The impact of the following covariates was investigated: a woman's serum AMH level, age, height, weight and BMI and a man's age, height, weight, BMI, sperm volume and sperm motility and morphology. The analysis was performed with a machine learning (ML) approach. Models were fit on the training set (677 patients) and their predictive performance was then evaluated on the test set (170 patients). MAIN RESULTS AND ROLE OF CHANCE: After ovarian stimulation and oocyte insemination, 40.1% of couples had at least one blastocyst available for the PGT-A. Of 1068 blastocysts analysed, 33.6% were euploid. Two distinct ML models were fit: one for the probability of having at least one euploid blastocyst and one for the number of euploid blastocysts obtained. In the training set of patients, the variable importance plots of both models indicated that AMH and the woman's age are by far the most important predictors. Specifically, a positive association between the outcome and AMH and a negative association between the outcome and female age appeared. Gradient-boosted modelling offers a greater predictive performance than generalized additive models (GAMs). LIMITATIONS, REASONS FOR CAUTION: The study was performed based on data from a single centre. While this provides a robust set of data with a constant ART process and laboratory practice, the model might be suitable only for the evaluated population, which may limit the generalization of the model to other populations. WIDER IMPLICATIONS OF THE FINDINGS: ML models indicate that for couples entering the IVF/PGT-A programme, ovarian reserve, which is known to vary with age, is the most important predictor of having at least one euploid embryo. According to the GAM, the probability of a 30-year-old woman having at least one euploid embryo is 28% or 47% if her AMH level is 1 or 3 ng/ml, respectively; if the woman is 40 years old, this probability is 18% with an AMH of 1 ng/ml and 30% with an AMH of 3 ng/ml. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by an unrestricted grant from Gedeon Richter. The authors declared no conflict of interests. TRIAL REGISTRATION NUMBER: N/A.

Dose adjustment of follicle-stimulating hormone (FSH) during ovarian stimulation as part of medically-assisted reproduction in clinical studies: a systematic review covering 10 years (2007-2017).

BACKGROUND: Individualization of the follicle-stimulating hormone (FSH) starting dose is considered standard clinical practice during controlled ovarian stimulation (COS) in patients undergoing assisted reproductive technology (ART) treatment. Furthermore, the gonadotropin dose is regularly adjusted during COS to avoid hyper- or hypo-ovarian response, but limited data are currently available to characterize such adjustments. This review describes the frequency and direction (increase/decrease) of recombinant-human FSH (r-hFSH) dose adjustment reported in clinical trials. METHODS: We evaluated the proportion of patients undergoing ART treatment who received ≥ 1 r-hFSH dose adjustments. The inclusion criteria included studies (published Sept 2007 to Sept 2017) in women receiving ART treatment that allowed dose adjustment within the study protocol and that reported ≥ 1 dose adjustments of r-hFSH; studies not allowing/reporting dose adjustment were excluded. Data on study design, dose adjustment and patient characteristics were extracted. Point-incidence estimates were calculated per study and overall based on pooled number of cycles with dose adjustment across studies. The Clopper-Pearson method was used to calculate 95% confidence intervals (CI) for incidence where adjustment occurred in < 10% of patients; otherwise, a normal approximation method was used. RESULTS: Initially, 1409 publications were identified, of which 318 were excluded during initial screening and 1073 were excluded after full text review for not meeting the inclusion criteria. Eighteen studies (6630 cycles) reported dose adjustment: 5/18 studies (1359 cycles) reported data for an unspecified dose adjustment (direction not defined), in 10/18 studies (3952 cycles) dose increases were reported, and in 11/18 studies (5123 cycles) dose decreases were reported. The studies were performed in women with poor, normal and high response, with one study reporting in oocyte donors and one in obese women. The median day that dose adjustment was permitted was Day 6 after the start of treatment. The point estimates for incidence (95% CI) for unspecified dose adjustment, dose increases, and dose decreases were 45.3% (42.7, 48.0), 19.2% (18.0, 20.5), and 9.5% (8.7, 10.3), respectively. CONCLUSIONS: This systematic review highlights that, in studies in which dose adjustment was allowed and reported, the estimated incidence of r-hFSH dose adjustments during ovarian stimulation was up to 45%.

Maternal age affects the relationship of basal FSH and anti-Müllerian hormone concentrations with post-ICSI/IVF live birth.

RESEARCH QUESTION: Does the association of basal FSH and anti-Müllerian hormone (AMH) concentrations with post-IVF/intracytoplasmic sperm injection (ICSI) live birth change with maternal age? DESIGN: A total of 2003 IVF/ICSI patients were stratified according to basal FSH/AMH in concordant favourable (CF; AMH >1 ng/ml and FSH ≤10 IU/l), concordant unfavourable (CU; AMH ≤1 ng/ml and FSH >10 IU/l), discordant with favourable AMH (DFA) and discordant with favourable FSH (DFF) groups, as well as according to age in pre-advanced maternal age (pre-AMA; <35), AMA-1 (≥35, ≤37), AMA-2 (>37, ≤40) and AMA-3 (>40). IVF/ICSI outcomes were compared among CF, CU, DFA and DFF groups, and the association of basal FSH and AMH concentrations with live birth was tested by univariate and multivariate analysis in total, pre-AMA and AMA groups, separately. RESULTS: Different outcome patterns were observed in discordant AMH/FSH groups from different age categories; favourable basal FSH concentrations were associated with higher delivery rates in pre-AMA patients, but with lower delivery rates in AMA groups. Within pre-AMA patients, DFF patients presented higher delivery rates but lower oocyte yield compared with DFA patients. In the univariate analysis, favourable AMH (P < 0.02) and oocyte yield (P < 0.002) were positively associated with live birth in all AMA groups. The multivariate analysis revealed that favourable basal FSH, but not AMH or oocyte yield, is associated with live birth in pre-AMA patients independently of other variables (P = 0.012). CONCLUSIONS: The relationship of basal FSH and AMH with IVF/ICSI success changes with maternal age; basal FSH better reflects clinical outcomes probably determined by oocyte quality in pre-AMA patients, while AMH better suits AMA patients.

Perinatal and obstetric outcomes in singleton pregnancies following fresh versus cryopreserved blastocyst transfer: a meta-analysis.

The transfer of cryopreserved blastocysts is increasing in IVF centres. However, little is known about the perinatal and obstetric outcomes of this procedure. In an attempt to further elucidate these issues, a systematic review and meta-analysis was conducted to compare cryopreserved transfer with fresh blastocyst embryo transfer. The results show that the risk of both preterm (odds ratio [OR] 0.89, 95% confidence interval [CI] 0.80-0.99, P = 0.04) and low birthweight births (OR 0.82, 95% CI 0.68-0.99, P = 0.04) was significantly lower after cryopreserved blastocyst transfer than after fresh blastocyst transfer. The rate of large for gestational age births was significantly higher (OR 1.68, 95% CI 1.55-1.82, P < 0.00001) and the rate of small for gestational age births significantly lower (OR 0.59, 95% CI 0.54-0.65, P < 0.00001) after cryopreserved blastocyst transfer. The transfer of cryopreserved blastocysts was associated with a significantly lower risk of placental abruption (OR 0.58, 95% CI 0.40-0.83, P = 0.003) but a significantly higher risk of Caesarean section (OR 1.21, 95% CI 1.01-1.43, P = 0.03). In conclusion, the perinatal and obstetric outcomes associated with the transfer of cryopreserved blastocysts differ from those associated with fresh blastocyst transfer.

The interchangeability of two assays for the measurement of anti-Müllerian hormone when personalizing the dose of FSH in in-vitro fertilization cycles.

OBJECTIVE: Study the interchangeability of Roche Elecsys and Beckman Coulter Access anti-Müllerian Hormone (AMH) assays to select the gonadotropin starting dose in IVF cycles. METHODS: Patients' AMH was measured using both Elecsys and Access automated assays. AMH values were then used to calculate the FSH starting dose. The main outcome is the percentage of women that would have been stratified to a different dose of gonadotropin due to differences in AMH values from the two tests. RESULTS: The Access assay systematically gives higher values compared with the Elecsys assay (slope = 0.88). For Follitropin Alfa, the difference in starting dose was > 15% in 2/113 patients, when Access AMH was used instead of Elecsys. For Follitropin Delta the difference in the starting dose was >15% in 21/113 patients when using Access AMH. When considering women with high ovarian reserve, only 4/51 would have received a Follitropin Delta dose that exceeded a 15% difference using Access AMH as a substitute for the Elecsys value. CONCLUSIONS: The use of the Roche Elecsys or Beckman Coulter Access leads to modest differences in AMH values, which seem to little affect the calibration of FSH dose used for ovarian stimulation.

Fertility preservation for genetic diseases leading to premature ovarian insufficiency (POI).

PURPOSE: The current review aims to summarize the data available concerning the applicability of fertility preservation techniques to genetic conditions at risk of premature ovarian insufficiency (POI). METHODS: A literature review through the PubMed Database was carried out. RESULTS: About 10% of cases of POI is related to genetic diseases. The most frequent conditions associated with POI are Turner syndrome and fragile X pre-mutation; mutation of BRCA 1-2 genes and several other mutations and genetic syndromes have recently been highlighted, although they rarely occur. If a diagnosis is issued before POI onset, counseling on currently available fertility preservation techniques is advisable. In case of spontaneous menarche (this can occur variably depending on the mutation) established techniques like embryo or oocyte cryopreservation can be proposed, even if, in some cases, their effectiveness may be reduced by ovarian alterations connected to the mutation. Ovarian tissue cryopreservation has recently been defined as an established medical procedure for fertility preservation in young cancer patients and may be an option for prepubertal patients. However, it is still experimental in special populations with genetic diseases causing POI. New innovative experimental techniques, like in vitro maturation of immature oocytes (IVM) and vitro activation (IVA) of immature follicles on ovarian tissue, have shown limited but encouraging data and they will be probably available in the near future. For a correct risk-benefit evaluation, the following aspects should be considered: actual knowledge about the pathology-specific efficacy of the various techniques, the average age of onset of POI, the possible risks associated with the procedure in relation to the underlying pathology, the probability of spontaneous conception, as well as the health implications of a possible future pregnancy.. CONCLUSIONS: Fertility preservation techniques represent a crucial opportunity for patients with genetic risk of POI. Early diagnosis increases the chances to apply these techniques. No specific recommendations concerning fertility preservation for each genetic pathology are available, and clinicians should first counsel the patient and her relatives about known risks and benefits of the available techniques, both those established and those considered as experimental.

Elevated levels of nitrous dioxide are associated with lower AMH levels: a real-world analysis.

STUDY QUESTION: Are there any associations between environmental pollutants and ovarian reserve, expressed by anti-Mullerian hormone (AMH) serum levels? SUMMARY ANSWER: In this first real-world approach to demonstrate the relationship between air pollutants and serum AMH levels, adverse associations were observed for nitrogen dioxide (NO2) but not with particulate matter. WHAT IS KNOWN ALREADY: In recent years, air pollution has emerged as a potential disrupter to the homeostasis of physiological hormones, possibly affecting human reproduction. Although the influence of age and smoking on AMH levels is largely accepted, the relationship between AMH and the environment has not currently been established. STUDY DESIGN, SIZE, DURATION: A longitudinal, observational, retrospective, real-world study was carried out, including all AMH measurements performed in a single laboratory from January 2007 to October 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Serum AMH data were connected to patients' age and residential address, to include air pollution data after geo-localisation. The air pollution considered daily particulate matter (PM) and NO2 values. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 1463 AMH measurements were collected (mean 1.94 ng/ml, median 0.90 ng/ml). AMH was inversely related to patients' age in women older than 25 years (adjusted R-squared 0.120, P < 0.001), but not in those younger than 25 years (adjusted R-squared 0.068, P = 0.055). AMH levels were inversely related to environmental pollutants, such as PM10 (Rho = -0.088, P = 0.001), PM2.5 (Rho = -0.062, P = 0.021) and NO2 (Rho = -0.111, P < 0.001). After subdividing the dataset into quartiles for PM10 and PM2.5, the influence of age on AMH serum levels was found to be a stronger influence than that exerted by PM (P = 0.833 and P = 0.370, respectively). On the contrary, considering NO2 quartiles, higher AMH levels were observed in third quartile compared to fourth quartile, even after adjustment for age (P = 0.028), indicating a stronger influence of NO2 exposure on AMH serum levels. Considering an AMH cut-off of 0.3 ng/ml, a significant higher frequency of women with severe ovarian reserve reduction in the fourth quartile was shown only for NO2 (P = 0.010). LIMITATIONS, REASONS FOR CAUTION: Several limitations should be underlined, such as the lack of information about work and life habits of each patient and the retrospective nature of the analysis performed on real-world data. WIDER IMPLICATIONS OF THE FINDINGS: Although the genetic component is highly predictive for defining the ovarian reserve at birth, potentially modifiable environmental factors could influence the rate of decline in AMH and ovarian reserve during adulthood. STUDY FUNDINGCOMPETING INTEREST(S): Authors have neither funding nor competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Comparison of euploidy rates of blastocysts in women treated with progestins or GnRH antagonist to prevent the luteinizing hormone surge during ovarian stimulation.

STUDY QUESTION: Does the prevalence of euploid blastocysts differ between patients treated with progestin primed ovarian stimulation (PPOS) and those treated with conventional ovarian stimulation? SUMMARY ANSWER: The numbers of blastocysts and euploid blastocysts per patient and the number of euploid embryos per injected oocyte are similar for patients undergoing progestin-primed ovarian stimulation and for those undergoing conventional ovarian stimulation with GnRH antagonist. WHAT IS KNOWN ALREADY: New approaches to ovarian stimulation have been developed based on the use of drugs administrable by mouth instead of via injections. Attention has been dedicated to progestins to block the LH surge. Previous data regarding the number of oocytes retrieved and the number of good-quality embryos generated in PPOS have demonstrated similar outcomes when compared to conventional ovarian stimulation, even if some concerns regarding the quality of embryos have been advanced. STUDY DESIGN, SIZE, DURATION: This is a prospective non-inferiority age-matched case-control study. In a period of 6 months, a total of 785 blastocysts from 1867 injected oocytes obtained from 192 patients were available for analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Infertile women undergoing IVF and preimplanation genetic testing (PGT) cycles were included. Forty-eight patients were treated with PPOS, and for each of them three age-matched historical controls (n = 144) treated with a GnRH antagonist protocol were selected. PGT was performed according to next-generation sequencing technology. MAIN RESULTS AND THE ROLE OF CHANCE: Basal characteristics were similar in the two groups; a substantial similarity of the main outcome measures in the two treatment groups has also been found. The rate of formation of euploid blastocysts per oocyte was 21% in both the two treatment groups. The percentage of patients with euploid embryos and the total number of euploid blastocysts per patient (median and interquartile range, IQR) in the PPOS group were 38.7 (25.5-52.9) and 2 (1.3-3.1), respectively. These figures were not significantly different in women treated with the GnRH antagonist protocol i.e. 42 (28-53.8) and 2.1 (1.3-2.9), respectively. LIMITATIONS, REASONS FOR CAUTION: This was a case-control study which may limit the reliability of the main findings. WIDER IMPLICATIONS OF THE FINDINGS: Our results encourage the use of PPOS, especially for oocyte donation, for fertility preservation and for patients in which total freezing of embryos is foreseen, for those expected to be high responders or candidates for preimplantation genetic testing. However, studies aiming to investigate the effect of PPOS on the live birth rate are warranted. STUDY FUNDING/COMPETING INTEREST(S): None.

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.

Testicular pain as an unusual presentation of COVID-19: a brief review of SARS-CoV-2 and the testis.

RESEARCH QUESTION: Can the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus induce testis damage and dysfunction? DESIGN: This is the description of the case of a young man presenting with heavy testicular pain as the first symptom of COVID-19 infection. A review of the literature is also presented. RESULTS: SARS-CoV-2 may enter into the host cell by binding to angiotensin-converting enzyme 2. This receptor seems to be widely expressed in different testicular cell types, making possible the occurrence of orchitis in male patients with COVID-19 infection. From a review of the literature, it seems that there is currently no evidence of sexual transmission of SARS-CoV-2; however, the possibility of virus-induced testis damage and dysfunction cannot be excluded. CONCLUSIONS: Further studies are necessary on the pathological effect of SARS-CoV-2 in the male reproductive system and to ensure a proper andrological follow-up for male patients.

Testing for SARS-CoV-2 (COVID-19): a systematic review and clinical guide to molecular and serological in-vitro diagnostic assays.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated coronavirus disease 2019 (COVID-19) pandemic has demanded rapid upscaling of in-vitro diagnostic assays to enable mass screening and testing of high-risk groups, and simultaneous ascertainment of robust data on past SARS-CoV-2 exposure at an individual and a population level. To meet the exponential demand in testing, there has been an accelerated development of both molecular and serological assays across a plethora of platforms. The present review discusses the current literature on these modalities, including nucleic acid amplification tests, direct viral antigen tests and the rapidly expanding laboratory-based and point of care serological tests. This suite of complementary tests will inform crucial decisions by healthcare providers and policy makers, and understanding their strengths and limitations will be critical to their judicious application for the development of algorithmic approaches to treatment and public health strategies.