Longitudinal study in adolescent anorexia nervosa: evaluation of cortico-striatal and default mode network resting-state brain circuits.

Anorexia nervosa (AN) typically emerges in adolescence. The cortico-striatal system (CSTS) and the default mode network (DMN) are brain circuits with a crucial development during this period. These circuits underlie cognitive functions that are impaired in AN, such as cognitive flexibility and inhibition, among others. Little is known about their involvement in adolescent AN and how weight and symptom improvement might modulate potential alterations in these circuits. Forty-seven adolescent females (30 AN, 17 healthy control) were clinically/neuropsychologically evaluated and scanned during a 3T-MRI resting-state session on two occasions, before and after a 6-month multidisciplinary treatment of the AN patients. Baseline and baseline-to-follow-up between-group differences in CSTS and DMN resting-state connectivity were evaluated, as well as their association with clinical/neuropsychological variables. Increased connectivity between the left dorsal putamen and the left precuneus was found in AN at baseline. At follow-up, body mass index and clinical symptoms had improved in the AN group. An interaction effect was found in the connectivity between the right dorsal caudate to right mid-anterior insular cortex, with lower baseline AN connectivity that improved at follow-up; this improvement was weakly associated with changes in neuropsychological (Stroop test) performance. These results support the presence of CSTS connectivity alterations in adolescents with AN, which improve with weight and symptom improvement. In addition, at the level of caudate-insula connectivity, they might be associated with inhibitory processing performance. Alterations in CSTS pathways might be involved in AN from the early stages of the disorder.

Perinatal outcomes in 6640 singleton pregnancies after donor oocyte IVF across three continents over 7 years.

PURPOSE: Are trends in singleton donor oocyte IVF perinatal outcomes consistent over time among four international ethnically diverse infertility centers? METHODS: This retrospective cohort consisted of an infertility network of four international IVF centers across three continents. Singleton live births resulting from fresh and frozen donor oocyte embryo transfers from January 1, 2012 to December 31, 2018 were included. The main outcome measures were birth weight (BW), preterm birth (PTB), large for gestational age (LGA), small for gestational age (SGA) and gestational age (GA) at delivery. RESULTS: The entire cohort (n = 6640) consisted of 4753 fresh and 1887 frozen donor oocyte embryo transfers. Maternal age, parity, body mass index, neonatal sex and GA at delivery were similar for fresh and frozen donor oocyte embryo transfers in the entire cohort and within each infertility center. All four centers had a trend of decreased BW and rates of PTB before 32 weeks annually, although significance was not reached. Three of the four centers had annual increased trends of PTB before 37 weeks and LGA newborns, although significance was not reached. BWs for the entire cohort for fresh and frozen donor embryo transfers were 3166 g ± 601 g and 3137 g ± 626 g, respectively. CONCLUSION: Similar trends in perinatal outcomes were present across four international infertility centers over 7 years. The overall perinatal trends in donor oocyte IVF may be applicable to centers worldwide, but further studies in more geographic regions are needed.

Perinatal outcomes in 13,626 singleton pregnancies after autologous IVF across three continents over 7 years.

PURPOSE: Are trends in singleton autologous IVF perinatal outcomes consistent over time among five international infertility centers? METHODS: This was a retrospective cohort study from January 1, 2012, to December 31, 2018. This study was performed through a large infertility network at five international infertility centers in which patients who had a singleton live birth resulting from fresh and frozen autologous IVF cycles were included. The primary outcome was live birth weight (BW) with secondary outcomes of preterm birth (PTB), large for gestational age (LGA), small for gestational age (SGA), and gestational age at delivery. RESULTS: The entire cohort (n = 13,626) consisted of 6941 fresh and 6685 frozen autologous IVF cycles leading to singleton deliveries. Maternal age, parity, body mass index, neonatal sex, and GA at delivery were similar for fresh and frozen IVF cycles in the entire cohort and within each infertility center. Four centers had a trend of decreased BW and three centers had decreased rates of PTB before 32 and 28 weeks and LGA newborns annually, although significance was not reached. Three IVF centers had annual increased trends of PTB before 37 weeks and four centers had increased rates of SGA newborns, although significance was not reached. CONCLUSION: Similar trends in perinatal outcomes were present across five international infertility centers over 7 years. Additional studies are crucial to further assess and optimize perinatal outcomes at an international level.

Is oocyte donation a risk factor for preeclampsia? A systematic review and meta-analysis.

PURPOSE: The objective of this meta-analysis is to determine whether there is a higher incidence of preeclampsia (PE) in pregnancies achieved by oocyte donation (OD) compared with pregnancies achieved by in vitro fertilization with autologous oocytes (IVF). METHODS: A systematic review was performed to identify relevant studies published from January 1994 until April 2015 with at least an abstract in English using PubMed, ISI Web of Knowledge, and clinicaltrials.gov. The 11 studies included in this systematic review were retrospective and prospective cohort studies of women reporting results on the association between oocyte donation vs. in vitro fertilization (exposure) and preeclampsia (outcome). RESULTS: Oocyte donation is a risk factor for the development of PE compared to IVF cycles, with a weighted OR of 3.12 under a fixed effects method (FEM: no heterogeneity between the studies). The weighted OR under a random effects model was 2.9 (REM: heterogeneity between the studies). The meta-regression analysis showed that neither multiple pregnancies (estimate = 0.08; p = 0.19) nor patient age (estimate = -2.29; p = 0.13) significantly explained the variability of the effect of oocyte donation on PE. Q statistic was 12.78 (p = 0.237), suggesting absence of heterogeneity between the studies. CONCLUSIONS: Pregnancies achieved by oocyte donation confer a threefold increase in the likelihood of developing PE than those achieved by in vitro fertilization with own oocytes. Physicians should be aware of this risk in order to both counsel patients and monitor pregnancies accordingly.

Empty follicle syndrome prevalence and management in oocyte donors.

STUDY QUESTION: Is the drug used for final oocyte maturation a factor in determining the prevalence of empty follicle syndrome (EFS)? SUMMARY ANSWER: The drug used for final oocyte maturation is not a factor in determining the prevalence of EFS among women unaffected by infertility. WHAT IS KNOWN ALREADY: Despite satisfactory follicular stimulation and adequate follicular development, cases of EFS, i.e. failure to recover any cumulus oocyte complex, have been reported both with hCG and GnRH agonist triggering. No standard management protocol has been proposed so far. STUDY DESIGN, SIZE, DURATION: Retrospective analysis of oocyte donation cycles performed between August 2006 and April 2013 in a large private fertility centre. PARTICIPANTS/MATERIALS, SETTING, METHODS: The analysis included 12 483 oocyte donation cycles of which 74 were EFS cycles. All cycles were triggered with either hCG or GnRH agonists. MAIN RESULTS AND THE ROLE OF CHANCE: There were no differences in the gonadotropic stimulation, pituitary suppression and triggering drug between cycles where oocytes were recovered successfully and EFS cycles. The total prevalence of EFS was 0.59%. Given the rarity of the syndrome, caution is advised when interpreting the analysis. LIMITATIONS, REASONS FOR CAUTION: The main limitation of this study is its retrospective nature. Although this is the largest analysis of EFS in donors reported so far, its statistical power is limited because the syndrome has a low incidence. In some cycles of EFS from 2006 to 2007 there is a lack of hormone data. WIDER IMPLICATIONS OF THE FINDINGS: Our findings may be generalized to oocyte donors and IVF patients younger than 35 years old, with cycles undergoing final maturation triggering with either hCG or GnRH agonists. The generalization cannot be extended to patients with an ovarian factor as the cause of their reproductive pathology. The theoretical aetiology of a temporary hypothalamic-pituitary hyposensitivity can explain the cycles where a rescue protocol with hCG has been successful. STUDY FUNDING/COMPETING INTERESTS: This work was supported in part by funding from Fundaciò EUGIN. The authors have no conflicts to declare. TRIAL REGISTRATION NUMBER: NA.

No association between LH levels and ovarian response in oocyte donors triggered with gonadotropin-releasing hormone agonist: A prospective study.

OBJECTIVE: Are circulating luteinizing hormone (LH) levels predictive of ovarian response in oocyte donors triggered with gonadotropin-releasing hormone (GnRH) agonists? STUDY DESIGN: A prospective cohort study with 224 oocyte donation cycles between 2021 and 2022 at a single center, examined the relationship between circulating luteinizing hormone (LH) levels and ovarian response. Oocyte donors underwent GnRH antagonist downregulation followed by GnRH agonist trigger. LH, estradiol, and progesterone levels were measured on day one of stimulation, trigger-day and 12 h post-trigger. Oocyte retrieval and maturity rates were analyzed using univariate and multivariate analyses, and the correlation between post-trigger LH levels and outcomes was assessed by Pearson's correlation test. A significance level of p < 0.05 was used. RESULTS: Mean age was 26 ± 4.3 years, mean body mass index (BMI, kg/m2) was 22.6 ± 3.2 and mean antral follicle count (AFC) was 21.7 ± 8.2. Post-trigger LH levels averaged 51.3 IU/L (SD 34.8), and oocyte retrieval rate and maturity rates were 112,7% (+/-48,1%) and 77,8% (+/- 17,2%), respectively. No significant differences were found in these outcomes for donors with post-trigger LH values below and above 15 IU/L (Mann Whitney's p > 0.05). However, exploratory analyses revealed that post-trigger LH values < 22 IU/L and basal LH levels < 4 IU/L were associated with significantly lower oocyte retrieval rate (90 % vs 110 %, p = 0.019 and 100 % vs 110 %, p = 0.019, respectively). CONCLUSIONS: This study, a first in exclusively focusing on oocyte donors, did not support the previously reported LH value of 15 IU/L as predictive of suboptimal ovarian response. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT05109403.

Functional MRI with a set-shifting task in adolescent anorexia nervosa: A cross-sectional and follow-up study.

Studies of set-shifting in adolescent AN present conflicting results, since not all have found differences with regard to controls. To date, no functional Magnetic Resonance Imaging (fMRI) studies have been carried out in adolescent patients, nor have patients been assessed after weight recovery. In this study, 30 female AN patients aged 12-17 and 16 matched control subjects were assessed both at baseline and after six months and renutrition using a structured diagnostic interview, clinical and neurocognitive scales, and fMRI during a set-shifting task. Adolescent AN patients presented similar performance on different neurocognitive tests and also on a set-shifting task during fMRI, but they showed a lower activation in the inferior and middle occipital and lingual gyri, fusiform gyri and cerebellum during the set-shifting task. No correlations were found between decreased activation and clinical variables such as body mass index, eating or depressive symptoms. After six months of treatment and renutrition in AN patients, there were no differences between patients and controls. These results show that adolescent AN patients have lower activation in relevant brain areas during a set-shifting task, and support the use of fMRI with set-shifting paradigms as a biomarker in future studies.

Risk of pre-eclampsia after fresh or frozen embryo transfer in patients undergoing oocyte donation.

OBJECTIVES: Different perinatal and neonatal adverse outcomes have been reported to be increased in frozen embryo transfer pregnancies compared with fresh embryo transfer with patient's own oocytes. Concerning preeclampsia, it has also been reported to be increased after frozen embryo transfer. The objective of this study is to asses if there is an increased risk of preeclampsia and gestational hypertension in pregnancies achieved with oocyte donation after frozen embryo transfer compared to fresh embryo transfer. STUDY DESIGN: Retrospective cohort study of 433 patients who underwent a cycle with donated oocytes either after fresh (n = 353) or frozen embryo transfer (n = 80) between March 2013 and April 2016 at a large fertility clinic. Participants are pregnant patients who reached the 20th week of gestation. The risk of preterm preeclampsia (presenting before 37 weeks of gestation), term preeclampsia (presenting at or after 37 weeks of gestation) and gestational hypertension are presented as unadjusted and adjusted odds ratio (OR). RESULTS: Frozen embryo transfer have similar risk for developing preterm preeclampsia compared to fresh embryo transfer, with an OR of 1.95 (CI 95% 0.72, 5.26, p = 0.18), as well as term preeclampsia (OR 0.3, 95%CI 0.04, 2.35, p = 0.25), and gestational hypertension (OR 1.45, 95% CI 0.75, 2.81, P = 0.27). CONCLUSIONS: Despite a high prevalence of preeclampsia in pregnancies achieved by oocyte donation, the freezing-thawing process does not confer more risk than the fresh embryo transfers in preterm preeclampsia, term preeclampsia or gestational hypertension.

Risk of preeclampsia in pregnancies resulting from double gamete donation and from oocyte donation alone.

INTRODUCTION: Pregnancies after gamete donation are at higher risk of developing pre-eclampsia (PE) than those achieved by IVF with patient's own gametes. We aim to assess whether pregnancies achieved with both oocyte and sperm donation (double donation, DD) are at an increased risk of developing PE and gestational hypertension (GH) compared to those achieved by oocyte donation alone (OD). MATERIALS AND METHODS: Retrospective cohort study of 433 patients who reached the 20th week of gestation with either DD (n = 81) or OD (n = 352) between March 2013 and April 2016 at a fertility clinic. The risk of preterm PE, term PE, and gestational hypertension (GH) are presented as unadjusted and adjusted odds ratio (OR). RESULTS: DD have a higher risk of preterm PE than OD, with an OR of 3.02 (95%CI 1.11-8.24; p = 0.031). We found no difference in the risk of term PE (OR 0.26, 95%CI 0.03-1.98; p = 0.19) or of GH (OR 1.23, 95% CI 0.63-2.43; p = 0.55). DISCUSSION: Pregnancies with DD are at higher risk of developing preterm PE than OD alone. Patients, and physicians treating them, should be made aware of the elevated risk of PE in these gestations, in order to start prophylactic measures during the first weeks of pregnancy.

Characteristics and clinical outcomes of patients undergoing fertility treatment by double gamete donation.

The number of women receiving in vitro fertilization cycles with both oocyte and sperm donation (double donation; DD) has grown globally in the last decade. The aim of this retrospective study, which included 1139 DD cycles, was to describe the characteristics of patients receiving DD and the outcomes of this assisted reproductive treatment. A cluster analysis identified couple 'status' as the main variable in dividing patients into categories. Three such status groups were identified for further analysis: (i) single women (SW), that is women without a partner either male or female; (ii) women with a male partner (MP); (iii) women with a female partner (FP). SW were significantly older (43.9) than patients with a MP (40.4) and a FP (41.3). Women with a male or FP comprised fewer patients with no previous assisted reproductive technology cycles (18.4% and 25.7%, respectively) compared to SW (43.5%). The proportion of patients without children before treatment was significantly different between SW (94.7%) and women with a MP (87.2%). There were no differences in clinical outcomes among the three groups studied. Biochemical pregnancy rate was 58.2% in SW, 58.4% in women with a MP and 64.9% in women with a FP. For the same groups, clinical pregnancy rates were 50.2%, 49.4% and 55.4%, while 'take-home baby' rates were 36.6%, 38.9% and 40.3%. Multiple birth and caesarean section rates were not different among the groups, with twinning rates 21.1%, 30.4% and 36%, and caesarean section rates 25.6%, 24% and 26.4% for SW, women with MP and women with FP, respectively.