Screening for perinatal depression and stress: a prospective cohort study.

PURPOSE: There is currently a heightened need for perinatal medical services to timely recognize and accurately meet the psychological needs of pregnant women. Psychological disturbances a mother experiences during pregnancy, such as depression and anxiety, can be later associated with inadequate maternal capacity for antenatal care for herself and the baby, and may lead to subsequent mental health problems later in the mother's life. Routine prenatal assessment could significantly benefit from being proactively enriched with early prevention mental health screening tools to assess, appropriately manage vulnerable populations, and subsequently implement preventive actions. METHODS: 178 pregnant women, under routine prenatal medical assessment, were measured regarding depressive symptomatology and stress, through the use of two validated psychometric tools (the Edinburgh Postnatal Depression Scale (EPDS) and the Perceived Stress Scale (PSS-14)). RESULTS: Heightened perceived stress and depressive symptomatology levels were associated with younger maternal age, an obstetrical record of more than one births and a history of abortion. Results additionally showed a connection between the requirement for a psychiatric referral-based on the levels of symptomatology recorded through the psychometric assessment and a clinical interview-and currently running the earlier stages (weeks) of pregnancy. CONCLUSION: Our revised proposed prenatal screening protocol for depression and stress suggests an amplified follow-up assessment including all pregnant women scoring high in both depression and in perceived stress, regardless of previous history of prenatal depression or of suicidality, to detect earlier or less manifest expressions of distress during pregnancy, in vulnerable perinatal populations.

Chronic Stress in Pregnancy Is Associated with Low Birth Weight: A Meta-Analysis.

BACKGROUND AND OBJECTIVES: Chronic activation of the stress system has cumulative effects on the body, and it places individuals at risk for adverse health outcomes. Chronic stress has been assessed by health questionnaires in pregnancy. During the perinatal period, mothers experience increased physical and emotional demands. Chronic stress interferes with hormonal functions in mothers and infants. This meta-analysis studies the effect of maternal chronic stress during pregnancy, as assessed by established stress questionnaires, on the birth weight of their full-term infants. DESIGN AND METHODS: According to our criteria and after research collection, we obtained 107 studies and we conducted two types of analyses: a logistic (N = 22,342) and linear regression analysis (N = 7431). RESULTS: Our results show that chronic stress is associated with a statistically significant risk of low birth weight (OR = 1.50, CI 95% = [1.13; 1.99], p ≤ 0.02). CONCLUSIONS: Increased maternal chronic stress, as assessed by questionnaires, in pregnancy is associated with a low-birth-weight baby. The above meta-analysis indicates that maternal high chronic stress questionnaire scores could be used as a clinical tool in order to assess low-birth-weight risk.

Primary follicular lymphoma of the uterine cervix: A case report.

Primary non-Hodgkin lymphoma of the uterine cervix is a rare clinical entity. The present case report describes an incidence of primary cervical follicular lymphoma, diagnosed during management of concurrent cervical intraepithelial neoplasia. The present case report outlines not only the necessity of adhering to guidelines regarding the management of abnormal cervical cytology, but also the importance of expert pathological review and the need for personalized management.

Acute iv CRH administration significantly increases serum active ghrelin in postmenopausal PCOS women compared to postmenopausal controls.

PURPOSE: In women with Polycystic Ovarian Syndrome (PCOS), an increased risk of disordered eating has been described. There is growing interest regarding a possible interconnection between psychological states and increased appetite in women with PCOS. Acute stress is characterized by increased Corticotropin Releasing Hormone (CRH) secretion. The aim was to estimate the ghrelin concentrations during CRH test. METHODS: Twenty postmenopausal women with PCOS and twenty age- and BMI- matched postmenopausal control women were recruited at Aretaieion University Hospital. In the morning (9 am) all subjects had anthropometric measurements (weight, height, waist circumference) and a fasting sample for hormonal measurements. An intravenous (iv) CRH stimulation test conducted over 1 min. Serum active ghrelin levels were measured at 0, 15, 30, 60, 90, 120 min after iv CRH administration. RESULTS: The postmenopausal PCOS group had a higher waist circumference compared to postmenopausal controls. Active ghrelin concentrations increased significantly from 0 to 15 min, to 30 min, to 60 min, to 90 min and then decreased to 120 min. However, within the postmenopausal control group there were no significant changes in serum active ghrelin levels. Serum active ghrelin concentrations were significantly greater in the postmenopausal control group at 0, 15 and 120 min compared to the postmenopausal PCOS group. At 90 min active ghrelin concentrations were significantly greater in the postmenopausal PCOS group. Delta Area Under the Curve of active ghrelin (ΔAUCghr) was significantly greater in the postmenopausal PCOS group compared to controls. CONCLUSIONS: In postmenopausal PCOS, but not in postmenopausal controls, iv CRH administration induces increased serum active ghrelin secretion, suggesting a possible anti-stress adaptive mechanism. An increase in serum active ghrelin may induce hunger as a side-effect of this presumed adaptive mechanism.

The impact of semen parameters on ICSI and pregnancy outcomes in egg recipient cycles with PGT-A.

BACKGROUND: The egg donation model offers an opportunity to isolate the male factor and evaluate its impact on IVF-intracytoplasmic sperm injection and pregnancy outcomes. OBJECTIVE: To study the effect of non-obstructive azoospermia on intracytoplasmic sperm injection and pregnancy outcomes compared with severe oligozoospermia and mild-to-moderate oligozoospermia in egg recipient cycles. MATERIALS AND METHODS: This is a retrospective longitudinal cohort study, including 1594 patients who underwent intracytoplasmic sperm injection in egg recipient cycles with preimplantation genetic testing for aneuploidies. The cohort was divided into three groups: couples with non-obstructive azoospermia accounting for 479 patients (30%); couples with severe oligozoospermia (sperm number <5 × 106 /mL), accounting for 442 patients (27.8%); couples with mild-to-moderate oligozoospermia, with sperm number >5 × 106 and <15 × 106 /mL, accounting for 673 patients (42.2%). RESULTS: The fertilisation rate was significantly reduced in the non-obstructive azoospermia group as compared with the severe oligozoospermia and the mild-to-moderate oligozoospermia group: 30.3% versus 63% and 77.3% (p < 0.05). Logistic regression analysis adjusted for confounders highlighted non-obstructive azoospermia as a negative predictor of obtaining a euploid blastocyst both per injected oocyte and per obtained blastocyst. The miscarriage rate in the non-obstructive azoospermia group was 11.8%; higher than the severe oligozoospermia and mild-to-moderate oligozoospermia groups (7% and 2.7%) (p < 0.05). The live birth rate per embryo transfer (ET) was significantly lower in the non-obstructive azoospermia group compared with the severe oligozoospermia and the mild-to-moderate oligozoospermia group (20.4% vs. 30.3% and 35.4%, p < 0.05). The risk of preterm labour was significantly higher in the non-obstructive azoospermia group, compared with the severe oligozoospermia and mild-to-moderate oligozoospermia group (55.1% vs. 46.8% and 16.1%, p < 0.001), and this difference was observed in both singleton and twin pregnancies. DISCUSSION AND CONCLUSION: In our retrospective comparative study, non-obstructive azoospermia significantly affects early embryonic potential and live birth rates per cycle and per embryo transfer. It is also associated with higher risk of preterm birth. Future prospective multi-centre studies are needed to highlight the effect of sperm quality on ART and pregnancy outcomes.

Daughters of polycystic ovary syndrome pregnancies and androgen levels in puberty: a Meta-analysis.

Purpose: To provide an overview and critical analysis of the literature related to the circulating androgen levels of daughters of PCOS mothers during prepubertal and pubertal stage who have not yet been diagnosed with PCOS or precocious puberty. Methods: We critically considered and meta-analyzed observational studies comparing androgens concentration in daughters of PCOS mothers compared to daughters of mothers without PCOS. A literature search was conducted in MEDLINE, Scopus and other sources from 01/09/2021 until 01/12/2021. The study followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). The primary outcome included total testosterone levels whereas the secondary outcomes included 17a-hydroxyprogesterone (17-OHP), androstenedione (Δ4Α) and Sex Hormone Binding Globulin (SHBG) levels respectively. Results: Our search yielded 1073 studies, 9 of which were included in our analysis. The results are presented differently according to pubertal stage. Pubertal daughters of PCOS mothers exhibited significantly higher total testosterone (pooled mean difference 14.95 (95%CI: 6.98 to 22.93), higher 17-OHP (pooled mean difference 0.11 (95%CI: 0.02 to 0.20) and lower SHBG levels (pooled mean difference -10.48 (95%CI: -16.46 to -4.61). Instead, prepubertal daughters of PCOS mothers presented greater SHBG levels (pooled mean difference 7.79 (95%CI: 0.03 to 15.54) compared to controls. No difference was found in Δ4Α levels in both groups. Conclusion: The onset of puberty is a critical point in the development of the disease and an early intervention may be imperative.

Presence of antiphospholipid antibodies is associated with increased implantation failure following in vitro fertilization technique and embryo transfer: A systematic review and meta-analysis.

PURPOSE: A systematic review and meta-analysis was conducted comparing the presence of anti-phospholipid (anti-PL) antibodies between women of reproductive age, without diagnosis of antiphospholipid syndrome, who experienced at least two implantation failures following in vitro fertilization and embryo transfer (IVF-ET), and either women who had a successful implantation after IVF-ET or women with at least one successful spontaneous pregnancy or unselected healthy fertile women with no history of IVF-ET. METHODS: Systematic search of the literature and meta-analysis of the relevant studies studying presence of antiphospholipid antibodies in women experiencing at least two implantation failures in IVF-ET as compared to either women who had a successful implantation after IVF-ET or/and women with at least one successful spontaneous pregnancy or unselected healthy fertile women with no history of IVF-ET. Six hundred ninety-four published reports were retrieved; 17 of them fulfilled the inclusion criteria set. RESULTS: Presence of either any type of anti-phospholipid or anticardiolipin antibodies or lupus-anticoagulant in women experiencing at least two implantation failures in IVF-ET was associated with increased implantation failure compared to women who had a successful implantation after IVF-ET (relative risk, RR: 3.06, 5.06 and 5.81, respectively). Presence of either anticardiolipin or lupus-anticoagulant or anti-beta2 glycoprotein-I or anti-phosphatidylserine antibodies in women experiencing at least two implantation failures in IVF-EΤ was associated with increased implantation failure compared to unselected healthy fertile women with no history of IVF-ET (RR:13.92, 6.37, 15.04 and 164.58, respectively). CONCLUSION: The prevalence of antiphospholipid antibodies, particularly that of anti-beta2 glycoprotein-I and anti-phosphatidylserine antibodies, in women experiencing at least two implantation failures in IVF-ET without diagnosis of antiphospholipid syndrome is significantly greater than either in women who had a successful implantation after IVF-ET or women with at least one successful spontaneous pregnancy or unselected healthy fertile women with no history of IVF-ET. TRIAL REGISTRATION NUMBER: PROSPERO ID: CRD42018081458.

Time to full effect, following treatment with combined oral contraceptives (cyclic versus continuous administration) in patients with endometriosis after laparoscopic surgery: a prospective cohort study.

The risk of recurrence after surgery is a major problem in women who are suffering from endometriosis. The prescription oral contraceptives (OCs) in the treatment of endometriosis-related pain, in women who do not desire fertility, is still controversial. The aim of this prospective cohort study is to evaluate the time until the reduction in the mean intensity of dysmenorrhoea and deep dyspareunia takes effect, for patients who use combined OCs in the accepted cyclic manner, versus in the continuous fashion as after the laparoscopic excision of endometriosis. A total of 28 patients diagnosed with endometriosis who underwent surgical treatment were offered at least a 12 months course of oral contraceptives. The intensity of both symptoms was reduced at the end of observational period in both groups. The use of continuous OCs (11 patients) was associated with a more pronounced reduction in the mean intensity of dyspareunia and dysmenorrhoea at 9 (p = 0.004) and 6 (p = 0.003) months respectively as compared to the cyclic group (17 patients).

Maternal spindle transfer for mitochondrial disease: lessons to be learnt before extending the method to other conditions?

Mitochondrial diseases are a group of conditions attributed to mutations of specific genes that regulate mitochondrial function. Maternal spindle transfer (MST) has been proposed as a method to prevent the transmission of these diseases and utilisation of the technique resulted in the birth of a baby free of disease in 2017 in Mexico. Potential flaws in research governance and the associated criticism emerged from the expansion of MST to provide a potentially new assisted reproductive technique to overcome infertility problems characterised by repeated in vitro embryo development arrest caused by mitochondrial dysfunction and cytoplasmic deficiencies of the oocyte. This applied technique represents a good example of the need to strike "a balance between taking appropriate precautions and hampering innovation". The purpose of this article is to explore, through a comprehensive literature search, whether and how this process can evolve from an experimental method to treat a medical condition to a standard of care solution for certain types of infertility. We argue that a number of key issues should be considered before applying the technique more broadly. These include regulatory oversight, safety and efficacy, cost, implications for research, essential laboratory skills and oversight, as well as the care needs of patients and egg donors.

New Incretin Combination Treatments under Investigation in Obesity and Metabolism: A Systematic Review.

The worldwide upward trend in obesity in adults and the increased incidence of overweight children suggests that the future risk of obesity-related illnesses will be increased. The existing anti-obesity drugs act either in the central nervous system (CNS) or in the peripheral tissues, controlling the appetite and metabolism. However, weight regain is a common homeostatic response; current anti-obesity medications show limited effectiveness in achieving long-term weight loss maintenance; in addition to being linked to various side effects. Combined anti-obesity medications (per os or injectable) target more than one of the molecular pathways involved in weight regulation, as well as structures in the CNS. In this systematic review, we conducted a search of PubMed and The ClinicalTrials.gov up to February 2021. We summarized the Food and Drug Administration (FDA)-approved medications, and we focused on the combined pharmacological treatments, related to the incretin hormones, currently in a clinical trial phase. We also assessed the mechanism of action and therapeutic utility of these novel hybrid peptides and potential interactions with other regulatory hormones that may have beneficial effects on obesity. As we improve our understanding of the pathophysiology of obesity, we hope to identify more novel treatment strategies.

Maternal Prenatal Stress, Thyroid Function and Neurodevelopment of the Offspring: A Mini Review of the Literature.

Fetal brain is extremely plastic and vulnerable to environmental influences that may have long-term impact on health and development of the offspring. Both the Hypothalamic-Pituitary-Adrenal (HPA) and the Hypothalamic-Pituitary-Thyroid (HPT) axes are involved in stress responses, whereas, their final effectors, the Glucocorticoids (GCs) and the Thyroid Hormones (TH s), mediate several fundamental processes involved in neurodevelopment. The effects of these hormones on brain development are found to be time and dose-dependent. Regarding THs, the developing fetus depends on maternal supply of hormones, especially in the first half of pregnancy. It is acknowledged that inadequate or excess concentrations of both GCs and THs can separately cause abnormalities in the neuronal and glial structures and functions, with subsequent detrimental effects on postnatal neurocognitive function. Studies are focused on the direct impact of maternal stress and GC excess on growth and neurodevelopment of the offspring. Of particular interest, as results from recent literature data, is building understanding on how chronic stress and alterations of the HPA axis interacts and influences HPT axis and TH production. Animal studies have shown that increased GC concentrations related to maternal stress, most likely reduce maternal and thus fetal circulating THs, either directly or through modifications in the expression of placental enzymes responsible for regulating hormone levels in fetal microenvironment. The purpose of this review is to provide an update on data regarding maternal stress and its impact on fetal neurodevelopment, giving particular emphasis in the interaction of two axes and the subsequent thyroid dysfunction resulting from such circumstances.

Poor Adherence to the Screening-Based Strategy of Group B Streptococcus Despite Colonization of Pregnant Women in Greece.

Group B streptococcus (GBS) is a leading cause of serious neonatal infections. Maternal GBS colonization is associated with early- and late-onset neonatal disease (EOD/LOD). In Greece, a screening-based strategy is recommended, in which concurrent vaginal-rectal cultures should be obtained between 36 0/7 and 37 6/7 weeks' gestation. We sought to examine the level of adherence to the GBS screening guidelines and estimate the prevalence of GBS colonization among pregnant women. Although in Greece the screening-based strategy is followed, we also examined known EOD risk factors and linked them to GBS colonization. A cross-sectional study of 604 women postpartum in three hospitals and maternity clinics was conducted. Following written informed consent, data were collected via a short self-completed questionnaire and review of patients' records. In 34.6% of the enrolled pregnant women, no culture had been taken. Of the remaining, 12.8% had proper vaginal-rectal sample collections. The overall maternal colonization rate was 9.6%. At least one risk factor for EOD was identified in 12.6% of participants. The presence of risk factors was associated with positive cultures (p = 0.014). The rate of culture collection did not differ between women with or without an EOD risk factor. Adherence to a universal screening of pregnant women with vaginal-rectal cultures was poor. Despite probable underestimation of GBS carrier status, almost 1 in 10 participants were GBS positive during pregnancy. Screening of women with risk factors for EOD should, at least, be prioritized to achieve prevention and prompt intervention of EOD.

Relationship Between Maternal Bone Biomarkers and Fetal Adiposity Through Normal Pregnancy.

PURPOSE: To examine the association of maternal bone markers [sclerostin, soluble receptor activator of nuclear factor-κB ligand (sRANKL), osteocalcin, 25-hydroxyvitamin D3] with fetal intra-abdominal and subcutaneous adipose tissue deposition and birthweight during normal pregnancy. METHODS: One hundred pregnant women (aged 30.4 ±â€…5.6 years, mean ±â€…SD) with prepregnancy body mass index = 24.1 ±â€…4.6 kg/m2 were seen prospectively during each trimester. At each visit they were submitted to anthropometric measurements, a fasting blood sampling, a 75-g oral glucose tolerance test, and a fetal ultrasonogram. At birth, neonates had birth weight measurement. RESULTS: In the second trimester, maternal sclerostin concentrations correlated positively with fetal abdominal circumference and birth weight; maternal sRANKL concentrations correlated positively with fetal abdominal subcutaneous fat thickness, sagittal abdominal diameter, and abdominal circumference. Fetuses born to mothers with greater (>254 ng/mL), compared to fetuses born to mothers with lower (≤254ng/mL), sRANKL concentrations had greater abdominal circumference, sagittal diameter, and abdominal subcutaneous fat thickness. Maternal serum sclerostin concentrations were the best positive predictors of birth weight. In the third trimester maternal sclerostin concentrations correlated positively with fetal sagittal abdominal diameter; maternal sRANKL concentrations positively correlated with fetal abdominal circumference and fetal abdominal sagittal diameter. CONCLUSIONS: Maternal bone markers sclerostin and sRANKL may relate to fetal intra-abdominal adipose tissue deposition through as yet unknown direct or indirect mechanisms, thus contributing to birthweight.

The addition of clomiphene citrate to ovarian stimulation protocols for poor responders.

Poor ovarian response (POR) is one of the most challenging problems in assisted reproduction. Several strategies have been used to improve pregnancy rates. The use of Clomiphene Citrate (CC) has been shown to improve ovarian stimulation outcomes and decrease gonadotropin requirements in women of advanced reproductive age. However, the combination of CC and gonadotropins to improve pregnancy rates after in IVF in poor responders is still unexplored due to the small number of trials with few participants. This is a prospective cohort trial involving 12 patients diagnosed with poor ovarian response who underwent ovarian stimulation during the period between June 2015 and September of 2017. All patients were treated with the maximum dose of gonadotropins (hMG, 300 IU/day, hMG group) according to a short gonadotropin/GnRH antagonist protocol. In a subsequent cycle those patients underwent the same stimulation protocol with the addition of 100 mg of CC from day 3 to day 7 (CC-hMG group). Supplementation with 100 mg of CC resulted in a statistically significant increase in estradiol levels, number of follicles and number of oocytes retrieved, as well as an increase in the number of total embryos available for transfer. Furthermore, a significant reduction was observed in cancellation rates in the CC-hMG group. Two clinical pregnancies, which resulted in two live births and 3 biochemical pregnancies were achieved in the CC/hMG group. Furthermore, by employing open-source, biological data we identified a common gene (Estrogen Receptor 1, ESR1) between genetic targets of clomiphene treatment and POR which could explain the benefits of clomiphene in this group of patients. In conclusion, the addition of CC 100 mg to the stimulation regimen in women diagnosed with POR and previous failed IVF cycles could improve stimulation results, but this study could not demonstrate any benefit in terms of clinical pregnancies and live births. The effectiveness of this treatment requires further investigation.

Combinational approach of retrospective clinical evidence and transcriptomics highlight AMH superiority to FSH, as successful ICSI outcome predictor.

OBJECTIVE: Combination of transcriptomic and retrospective clinical data, to assess anti-Mullerian hormone (AMH) functionality at a cumulus cell level and evaluate AMH potential as a suitable marker for IVF outcomes (oocytes retrieved, number of day 3 embryos, gestation outcomes). DESIGN: Raw RNA-sequencing data of cumulus cells sourced from younger (n = 10) patient group (group A) (age 29 (1 year of age), baseline FSH 7.4 (0.5 mIU/ml), AMH 4.67 (1.56 ng/ml)) and older (n = 10) patient group (group B) (age 43 (± 0.55 years of age), baseline FSH 8 (0.8 mIU/ml), AMH 1.07 (0.44 ng/ml)) were employed to derive transcriptomic differences among high vs. low AMH groups. We collected retrospectively patient data from 80 infertile patients selected according to pre-specified inclusion criteria. SETTING: Publicly available raw RNA-sequencing data were retrieved from the SRA database of NCBI resource GEO Accession (GSM21575/35-44; GEO Accession: GSM21575/45-55). Retrospective data were collected from referrals to the Institute of Reproductive Medicine, Lito Hospital of Athens and the Institute of Life, Iaso Hospital of Athens, between the periods of March 2015 and April 2018. INTERVENTION(S): A fixed human menopausal gonadotropin (hMG) antagonist protocol was used for all patients. All patients had serum AMH levels measured within a 3-month period prior to stimulation and serum levels of FSH and estradiol (day 2 of menstrual cycle; E2) (Clinical Trial code NV24042014). MAIN OUTCOME MEASURE(S): The primary outcomes were identification of transcriptomic variations among high (group A) vs. low (group B) AMH patients. Retrospective data primary outcomes were number of oocytes retrieved, fertilized successfully (grades A and B, day 2 embryos), and total number of day 3 embryos. Secondary outcome was live birth rate. Finally, we compared primary outcomes with AMH and FSH level as well as their genetic pathways (interacting genes) to demonstrate the predictive accuracy. RESULTS: Essential players of the AMH signaling cascade, namely, SMAD1, SMAD4, SMAD5, ALK1, and LEF1, were significantly upregulated in group A (n 10) transcriptome. This biological clue was further supported by retrospective clinical data (n 80 participants), where AMH was positively correlated with both oocytes retrieved and fertilized as well as number of day 3 (grades A and B) embryos from patients undergoing IVF, in a statistically significant manner. AMH was further positive trend of association with successful pregnancy outcomes. CONCLUSION: Overall, this study offers new insight on AMH effects upon cumulus cells and new aspects on how AMH might promote oocyte integrity and embryo viability at a biochemical level as well as add to the current body of evidence supporting AMH clinical potential as a more sensitive marker of IVF outcomes in comparison with FSH, regarding numbers of oocytes received and high-quality day 2 and day 3 embryos.

Cleavage Stage versus Blastocyst Stage Embryo Transfer in Oocyte Donation Cycles.

BACKGROUND AND OBJECTIVE: During the last few years, a trend has been noted towards embryos being transferred at the blastocyst stage, which has been associated with improved rates regarding implantation and clinical pregnancy in comparison to cleavage stage embryo transfers. There is a limited number of studies investigating this notion in oocyte donation cycles employing cryopreserved embryos. The aim of this study is to evaluate the implantation potential and clinical pregnancy rates between the day 3 cleavage stage and blastocyst stage embryo transfers in oocyte donation cycles employing vitrified embryos. METHODS: This is a retrospective evaluation of oocyte donation frozen-thawed transfers completed in our clinic from January 2017 to December 2017. Intracytoplasmic sperm injection was conducted for all oocytes. Following fertilization, all embryos were cryopreserved either at the cleavage or blastocyst stage. Embryo transfer of two embryos was performed under direct sonographic guidance in all cases. Results: Our results confirmed a 55.6% clinical pregnancy (CP) resulting from day 3 embryo transfers, a 68.8% CP from day 5, and 71.4% CP from day 6. Significantly improved pregnancy rates were related to embryo transfers at the blastocyst stage when compared to cleavage stage transfers (68.9% and 55.6% respectively, p = 0.016). The risk with regards to multiple pregnancies was similar. CONCLUSION: Our findings indicate that in oocyte donation cycles employing vitrified embryos, embryo transfer at the blastocyst stage is accompanied with a significant improvement in pregnancy rates and merits further investigation.

Ovarian granulosa cell tumor and clomiphene citrate resistance. A case report and review of the literature.

Granulosa cell tumors (GCTs) account for less than 5% of all ovarian malignancies, occur in younger ages, are usually diagnosed in their early stages, and have a good prognosis. GCTs usually present with features of hyperestrogenism. This paper reports the unusual case of an adult with a GCT with manifestations including amenorrhea, mild hirsutism, infertility, clomiphene citrate (CC) resistance (CC), mildly elevated testosterone, high anti-Müllerian hormone (AMH) and normal estrogen levels. The patient was initially diagnosed with polycystic ovarian syndrome (PCOS), and after four attempts at ovarian stimulation she was diagnosed with CC resistance. The patient later underwent laparoscopic evaluation on account of a solid mass on her left ovary. The pathology report described it as a borderline adult type GCT and four weeks after surgery she had a positive pregnancy test. Twelve months after delivery, the patient had no obvious symptoms of disease and her menstrual cycle was normal. Serial measurements of serum inhibin B, AMH, estrogen, and testosterone levels were within normal range. In conclusion, the resistance to clomiphene manifested by the patient might be explained by a potential mechanism implicating inhibin B and AMH due to the presence of a GCT. Further studies are required to evaluate the role of AMH and Inhibin B in the mechanism of CC resistance in women with PCOS.

Pregnancy Complications in a-Thalassemia (Hemoglobinopathy H): A Case Study.

Thalassemia intermedia (TI) is a clinical definition which represents a wide spectrum of thalassemia genotypes but mainly includes patients who do not require or only occasionally require transfusion. An uncommon case of a 32-year-old Greek woman, para 1, at the 22nd week + day 3 of gestation with thalassemia intermedia (she was splenectomized), where her pregnancy was complicated with portal vein thrombosis, splenic thrombosis, and partial HELLP, is described. This is a generally uncommon event in thalassemia intermedia. She had no transfusion as her hematologist consulted and she took anticoagulation therapy. Thus, we present for the first time in the literature a case of HbH a-thalassemia pregnant woman whose pregnancy was complicated with portal vein thrombosis, splenic vein thrombosis, and partial HELLP; she was treated with anticoagulation therapy and she had a successful outcome.

Low versus high volume of culture medium during embryo transfer: a randomized clinical trial.

PURPOSE: The aim of this prospective randomized control trial was to evaluate if the use of two different volumes (20-25 vs 40-45 µl) of media used for embryo transfer affects the clinical outcomes in fresh in vitro fertilization (IVF) cycles. METHODS: In total, 236 patients were randomized in two groups, i.e., "low volume" group (n = 118) transferring the embryos with 20-25 µl of medium and "high volume" group (n = 118) transferring the embryos with 40-45 µl of medium. The clinical pregnancy, implantation, and ongoing pregnancy rates were compared between the two groups. RESULTS: No statistically significant differences were observed in clinical pregnancy (46.8 vs 54.3%, p = 0.27), implantation (23.7 vs 27.8%, p = 0.30), and ongoing pregnancy (33.3 vs 40.0%, p = 0.31) rates between low and high volume group, respectively. CONCLUSION: Higher volume of culture medium to load the embryo into the catheter during embryo transfer does not influence the clinical outcome in fresh IVF cycles. TRIAL REGISTRATION NUMBER: NCT03350646.

Placenta and Umbilical Cord Cause in Antepartum Deaths.

Stillbirth is a sudden and painful event for parents and obstetrical specialists as well. It is, therefore, of greatest importance to be able to give answers for the cause in order to plan a subsequent pregnancy. The aim of this retrospective study is to estimate the placental and umbilical cord cause of intrauterine death in relation to different gestational ages. The study took place on the Medical Birth Registry of Aretaieio Hospital, National and Kapodistrian University, Athens, Greece. We include a total of 19,283 pregnancies from 1998 to 2012. In this study period, 431 embryonic deaths occurred. The clinical history was documented on admission at delivery. Conditions thought to be associated with the intrauterine fetal death were recorded. Gestational age was calculated from the last menstrual period as well as with the three-trimester system. The autopsy, placenta and umbilical cord examination were performed by the same laboratory of pathology in Aretaieio University Hospital. We found that the majority of stillbirths occurred in the second trimester. We examined placenta and umbilical cord in all cases. The most frequent histologic abnormalities were those indicated placental vascular insufficiency. As far as the umbilical cord is concerned we found that the inflammatory disorder was the most common in antepartum deaths. A single umbilical artery was significantly related to gestational diabetes and congenital embryonic anomalies. Finally, our results showed steady declines in antepartum deaths during 1998-2012. As a result, we reached the conclusion that in order to reduce the fetal death rate, we have to insist on the autopsy of the placenta and umbilical cord in order to gain the appropriate information in counseling the parents.