Myomectomy during pregnancy: an obstetric overview.

INTRODUCTION: Uterine fibroids (UFs) are the most common benign disease affecting female reproductive system, and occurring in 20-40% of women, and in 10% of pregnancies. The aim of the investigation was to summarize evidence about the management and treatment of UFs and related complications in pregnancy. EVIDENCE ACQUISITION: A literature review was performed using scientific databases, including all case report and case series, using a combination of key words related to the problem exposed. Data about gestational age at diagnosis, maximum fibroids diameter, type of surgery and gestational age at surgery, delivery and perinatal outcome were collected. Two clinical cases were also included. EVIDENCE SYNTHESIS: Sixty-six articles were selected, and 199 patients were included. In 76% of patients the gestational age at myomectomy was lower than 20 weeks, in 85% laparotomic surgery was chosen, in 41% of cases the maximum fibroid diameter was between 7-20 cm, in 41% of pregnancies the route of delivery was the Cesarean section. In the eight percent of cases there was a complication given by miscarriage, fetal demise or neonatal death. CONCLUSIONS: Myomectomy is a feasible procedure in those pregnancies complicated by symptomatic fibroids, though surgery in pregnancy is associated with an increased risk of obstetric complications.

Pregnancy Complications, Correlation With Placental Pathology and Neonatal Outcomes.

Purpose: We aimed to clarify and contribute to a better comprehension of associations and correlations between placental histological findings, pregnancy evolution, and neonatal outcomes. Study Design: This is a longitudinal and prospective observational study, performed between May 2015 and May 2019, on 506 pregnant women. Clinical data related to pregnancy outcome, neonatal health status, and placental histology were primarily collected. Twin pregnancies or malformed newborns were excluded and therefore the study was conducted on 439 cases. These cases have been then subdivided into the following study groups: (a) 282 placentas from pathological pregnancies; and, (b) a control group of 157 pregnancies over 33 weeks of gestational age, defined as physiological or normal pregnancies due to the absence of maternal, fetal, and early neonatal pathologies, most of which had undergone elective cesarean section for maternal or fetal indication. Results: A normal placenta was present in 57.5% of normal pregnancies and in 42.5% of pathological pregnancies. In contrast, placental pathology was present in 26.2% of normal pregnancies and 73.8% of pathological pregnancies. Comparison of the neonatal health status with the pregnancy outcome showed that, among the 191 newborns classified as normal, 98 (51.3%) were born from a normal pregnancy, while 93 (48.7%) were born from mothers with a pathological pregnancy. Among the 248 pathological infants, 59 (23.8%) were born from a mother with a normal pregnancy, while 189 (76.2%) were born from pregnancies defined as pathological. Conclusion: Placental histology must be better understood in the context of natural history of disease. Retrospective awareness of placental damage is useful in prevention in successive pregnancy, but their early identification in the evolving pregnancy could help in association with biological markers or more sophisticated instruments for early diagnosis.

Hormone therapy in female-to-male transgender patients: searching for a lifelong balance.

BACKGROUND: Reassignment of a female-to-male (FtM) person requires gender-affirming, androgenic hormonal treatment that is planned to induce appropriate structural changes. This therapy must be prolonged long term, even after the sex reassignment surgery (SRS). The purpose of this study is to evaluate the effects of hormone therapy with testosterone in FtM subjects during a 24-month follow-up in order to highlight the occasional need for early decompensation and to make adequate hormone therapy modulations. METHODS: Fifteen out of 23 FtM persons had been previously treated with SRS, while eight were still awaiting surgery. During hormone therapy, both groups were followed for 24 months, with evaluation of desired changes, adverse effects, and functional or metabolic indicators. RESULTS: In the group of operated FtM subjects (15/23), a significant increase of total testosterone (total T) and free testosterone (free T) was found after 24 months. Luteinizing hormone (LH) maintained a low level, decreasing after ovariectomy, while FSH increased. Voice deepening, facial and body hair variation, male-pattern balding, and body mass index (BMI) increase are all physical changes due to androgenization. In both groups of patients who have been closely monitored, the side effects and thromboembolic, metabolic, and cardiovascular risks of androgen therapy, even in the long term, appear to be irrelevant. CONCLUSION: Total T, free T, and LH dosages are shown to be reliable markers of correct androgenization. Strict monitoring of lipid profile, evaluation of BMI and hematocrit, avoidance of self-initiated therapeutic modifications, adherence to a healthy lifestyle, and avoidance of excessive daily calorie intake can limit risks linked to long-term testosterone administration. TRIAL REGISTRATION: Retrospectively registered.

Maternal total cell-free DNA in preeclampsia and fetal growth restriction: Evidence of differences in maternal response to abnormal implantation.

OBJECTIVES: Preeclampsia and fetal growth restriction are obstetrical syndromes associated with abnormal placental implantation and changes in the activation status of maternal leukocytes. This study is aimed to determine by a simple, rapid fluorescent assay the changes in maternal serum total cell-free DNA (t-cfDNA) concentrations in women with preeclampsia and those with fetal growth restriction (FGR). STUDY DESIGN: A cross-sectional study was conducted measuring maternal serum t-cfDNA concentrations. Women were classified into the following groups: 1) patients with preeclampsia (n = 21); 2) FGR-estimated fetal weight below the 10thpercentile (n = 28); and 3) normal pregnancy (n = 39). Serum samples were directly assayed for t-cfDNA using a rapid fluorescent SYBR Gold assay. Elevated maternal serum t-cfDNA concentrations were defined as a cutoff>850ng/ml. Nonparametric statistics were used for analysis. RESULTS: Women with preeclampsia had a higher median maternal serum concentration (802 ng/ml, 400-2272 ng/ml) than women with a normal pregnancy (499 ng/ml, 0-1892 ng/ml, p = 0.004) and those with FGR (484 ng/ml, 72-2187 ng/ml, p = 0.012). Moreover, even patients with FGR <5th percentile and abnormal Doppler had a lower median maternal serum t-cfDNA than those with preeclampsia (median 487 ng/ml, 144-1971 ng/ml, p = 0.022). The median concentration of t-cfDNA did not differ between women with a normal pregnancy and those with FGR (p = 0.54), as well as those with fetuses <5th percentile and abnormal Doppler (p = 0.7). Women with preeclampsia had a higher proportion of elevated t-cfDNA than those with a normal pregnancy (p = 0.015) and patients with FGR (p = 0.025). CONCLUSIONS: Preeclampsia is associated with higher maternal serum t-cfDNA concentration than normal pregnancy or FGR. This observation may reflect an increased systemic activation of the maternal inflammation, rather than placental; this assumption is supported by the fact that we did not observe a significant change in the maternal serum t-cfDNA in patients with placental-mediated FGR.

Obesity as disruptor of the female fertility.

Both obesity and overweight are increasing worldwide and have detrimental influences on several human body functions including the reproductive health. In particular, obese women undergo perturbations of the 'hypothalamic pituitary ovarian axis', and frequently suffer of menstrual dysfunction leading to anovulation and infertility. Besides the hormone disorders and subfertility that are common in the polycystic ovary syndrome (PCOS), in obesity the adipocytes act as endocrine organ. The adipose tissue indeed, releases a number of bioactive molecules, namely adipokines, that variably interact with multiple molecular pathways of insulin resistance, inflammation, hypertension, cardiovascular risk, coagulation, and oocyte differentiation and maturation. Moreover, endometrial implantation and other reproductive functions are affected in obese women with complications including delayed conceptions, increased miscarriage rate, reduced outcomes in assisted conception treatments.On the contrary, weight loss programs through lifestyle modification in obese women, have been proven to restore menstrual cyclicity and ovulation and improve the likelihood of conception.

Clinical management of a unique case of PNET of the uterus during pregnancy, and review of the literature.

RATIONALE: PNETs (primitive neuroectodermal tumors) are a family of highly malignant neoplasms characterized by small round cells of neuroepithelial origin. They usually involve bone and soft tissues, and have a higher incidence in childhood. PATIENT CONCERNS: In this case report, we describe the obstetric and oncological outcome of a huge mass diagnosed as a leiomyoma in a 39-year-old pregnant woman who complained of low back pain, dysuria, and urinary frequency at 22 weeks of gestation. DIAGNOSES: During the 25th week of pregnancy, the patient was referred to our hospital at night with severe anemia and suspected hemoperitoneum. She underwent an emergency caesarean section, delivering a female fetus weighing 400 g, with an Apgar score of 7 at 1 minute and 9 at 5 minutes. INTERVENTION: During surgery, we found a huge uterine sarcoma-like metastatic tumor, invading the pelvic peritoneum and parametria bilaterally; the adnexae seemed disease-free. We performed a type B radical hysterectomy, bilateral salpingo-oophorectomy, pelvic peritonectomy, omentectomy, appendectomy, and excision of a bulky lymph node. Seven days after delivery, staging computed tomography (CT) scan demonstrated a large lombo-aortic lymph node compressing the left renal vein and we completed debulking with a second surgery, including diaphragmatic peritonectomy and excision of a huge lymph node by lombo-aortic lymphadenectomy, requiring partial reconstruction of an infiltrated renal vein. OUTCOME: Ten days after the second surgery, echo-color Doppler showed a regular microcirculation in the left kidney. The patient was discharged after 10 days, and the baby after 1 month, both in good health.Histological examination revealed a uterine body cPNET (central primitive neuroectodermal tumor) orienting the clinical management toward chemotherapy with cisplatin and etoposide. LESSONS: PNETs are aggressive neoplasms, usually diagnosed at an advanced stage. Due to their low incidence, universally accepted guidelines are still unavailable. Radical surgery leaving no macroscopic residual disease is mandatory in advanced stages. A good fertility-sparing procedure can be performed only in young women at early stages of disease, when the wish for childbearing is not yet fulfilled.

In vitro differentiation of human oocyte-like cells from oogonial stem cells: single-cell isolation and molecular characterization.

STUDY QUESTION: Are the large cells derived from cultured DEAD box polypeptide 4 (DDX4)-positive oogonial stem cells (OSCs), isolated from the ovarian cortex of non-menopausal and menopausal women, oocyte-like cells? SUMMARY ANSWER: Under appropriate culture conditions, DDX4-positive OSCs from non-menopausal and menopausal women differentiate into large haploid oocyte-like cells expressing the major oocyte markers growth differentiation factor 9 (GDF-9) and synaptonemal complex protein 3 (SYCP3) and then enter meiosis. WHAT IS KNOWN ALREADY: The recent reports of OSCs in the ovaries of non-menopausal and menopausal women suggest that neo-oogenesis is inducible during ovarian senescence. However, several questions remain regarding the isolation of these cells, their spontaneous maturation in vitro, and the final differentiation state of the resulting putative oocytes. STUDY DESIGN, SIZE, DURATION: DDX4-positive OSCs were obtained from 19 menopausal and 13 non-menopausal women (who underwent hysterectomy for uterine fibroma, ovarian cyst, or other benign pathologies) and cultured for up to 3 weeks. Large and small cells were individually isolated and typed for early and late differentiation markers. PARTICIPANTS/MATERIALS, SETTING, METHODS: Ovarian cortex fragments were processed by immuno-magnetic separation using a rabbit anti-human DDX4 antibody and the positive populations were measured by assessing both FRAGILIS and stage-specific embryonic antigen 4 (SSEA-4) expression. After 3 weeks in culture, large oocyte-like cells were individually isolated by DEPArray based on PKH26 red staining and cell size determination. GDF-9 and SYCP3 as final, and developmental pluripotency-associated protein 3 (DPPA3) as primordial, germline markers were measured by droplet digital PCR. The haploid versus diploid chromosomal content of chromosomes X and 5 was investigated using fluorescence in situ hybridization (FISH). MAIN RESULTS AND THE ROLE OF CHANCE: SSEA-4+ and FRAGILIS+ subsets of DDX4-positive populations were present at lower mean levels in menopausal (SSEA-4+: 46.7%; FRAGILIS+: 47.5%) than in non-menopausal (SSEA-4+: 64.9%; FRAGILIS+: 64.8) women (P < 0.05). A comparison of the women's age with the ratio of DDX4-positive cells/cm3 of ovarian cortex revealed an inverse correlation with OSC number (P < 0.05). Once cultured, cells from both groups differentiated to form large (up to 80 µm) mature oocyte-like cells with typical oocyte morphology. Despite the higher numbers of these cells in cultures from non-menopausal women (37.4 versus 23.7/well; P < 0.001), the intra-culture percentages of large oocyte-like cells did not differ significantly between the two groups. Single large oocyte-like cells isolated from non-menopausal and menopausal women expressed equivalent levels of GDF-9 (e.g. 2.0 and 2.6 copies/µl RNA, respectively) and SYCP3 (e.g. 1.2 and 1.5 copies/µl RNA, respectively) mRNA. The remaining small cells isolated from the cultures expressed large amounts of DPPA3 mRNA (e.g. 5.0 and 5.1 copies/µl RNA, from menopausal and non-menopausal women, respectively), which was undetectable in the large oocyte-like cells. FISH analysis of the large and small cells using probes for chromosomes X and 5 revealed a single signal in the large cells, indicative of chromosome haploidy, whereas in the small cells two distinct signals for each chromosome indicated diploidy. LARGE SCALE DATA: Not applicable. LIMITATIONS, REASONS FOR CAUTION: Our study demonstrated the final differentiation of OSCs, collected from the ovarian cortex of adult women, to oocyte-like cells. However, because the rate of differentiation was low, a major role of the stem cell niche housing these OSCs cannot be ruled out. WIDER IMPLICATIONS OF THE FINDINGS: Since the ability of OSCs to generate mature oocytes in vitro is highly variable, the viability of these cells in the ovarian cortex of non-menopausal and menopausal women may well be determined by the stem cell niche and the woman's concurrent reproductive state. Our study showed that the oocyte-like cells obtained by OSC differentiation in vitro, including those from the OSCs of menopausal women, express markers of meiosis. This model of ovarian neo-oogenesis will contribute to the development of approaches to treat female infertility. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by Italian Association for Cancer Research (IG grant 17536), and from the Apulia Region ('Oncogenomic Project' and 'Jonico-Salentino Project'). All Authors declare no competing interests.

Surgical and pharmacological reassignment: influence on transsexual cardiovascular risk profile.

BACKGROUND/AIM: To evaluate and stratify early cardiovascular risk of transsexuals who underwent pharmacological and/or surgical gender reassignment. METHODS: Fifty-six transsexuals were divided into two groups: group 1 - underwent gonadectomy (orchiectomy for transwomen and hystero-annessiectomy for transmen); group 2 - hormone replacement therapy alone. All participants underwent carotid artery intima-media thickness (C-IMT) and flow-mediated vasodilation (FMD) of brachial artery evaluations. RESULTS: FMD was lower in patients who had undergone gonadectomy compared with non-surgically treated patients (Group 1: 5.711 vs Group 2: 7.339, P < 0.0001). Mean C-IMT was higher in group 1 than group 2 (group 1: 0.733 vs group 2: 0.582). The duration of hormone therapy correlates positively with mean C-IMT (B = 0.001) and negatively with FMD (%) (B = - 0.007). CONCLUSIONS: Cardiovascular risk, which is expressed in terms of endothelial (FMD) and morphological (C-IMT) dysfunction, increases in subjects undergoing gonadectomy compared with those receiving cross-sex reassignment therapy alone.

Epigenetic Matters: The Link between Early Nutrition, Microbiome, and Long-term Health Development.

Epigenetic modifications are among the most important mechanisms by which environmental factors can influence early cellular differentiation and create new phenotypic traits during pregnancy and within the neonatal period without altering the deoxyribonucleic acid sequence. A number of antenatal and postnatal factors, such as maternal and neonatal nutrition, pollutant exposure, and the composition of microbiota, contribute to the establishment of epigenetic changes that can not only modulate the individual adaptation to the environment but also have an influence on lifelong health and disease by modifying inflammatory molecular pathways and the immune response. Postnatal intestinal colonization, in turn determined by maternal flora, mode of delivery, early skin-to-skin contact and neonatal diet, leads to specific epigenetic signatures that can affect the barrier properties of gut mucosa and their protective role against later insults, thus potentially predisposing to the development of late-onset inflammatory diseases. The aim of this review is to outline the epigenetic mechanisms of programming and development acting within early-life stages and to examine in detail the role of maternal and neonatal nutrition, microbiota composition, and other environmental factors in determining epigenetic changes and their short- and long-term effects.