Successful Treatment of Infertility in a Patient with Probable 17 Hydroxylase Deficiency and Particularities of Association with Adrenal Autoimmunity-A Case Report and Review of the Literature.

Congenital adrenal hyperplasia (CAH) due to 17-hydroxylase deficiency (17OHD) is a rare disease accounting for less than 1% of cases of CAH. In female patients, fertility is severely affected mainly due to constantly increased progesterone affecting endometrium receptivity and implantation. The optimal treatment for infertility in these patients is not clearly established, with only a few recent case reports of successful pregnancies available in the literature. Hereby, we present the case of an infertile female patient with 17OHD who obtained pregnancy through an in vitro fertilization (IVF) freeze-all strategy and particularities of association with adrenal autoimmunity. A 32-year-old infertile female patient was referred for infertility evaluation and treatment. She had normal sex development and menstrual history with oligomenorrhea alternating with normal menstrual cycles. During the evaluation, a reduced ovarian reserve and obstruction of the left fallopian tube were identified, and IVF treatment was recommended. During a controlled ovarian stimulation for IVF, increased values of serum progesterone were observed; thus, all the embryos were frozen and additional tests were performed. Increased values of 17-hydroxyprogesteron, 11-deoxycorticosteron, and adrenocorticotropic hormones in association with low basal and stimulated serum cortisol, testosterone, androstenedione, and dehydroepiandrosterone sulfate were found, supporting the presence of 17OHD. She started treatment with oral hydrocortisone given at 20 mg/day but, because follicular phase serum progesterone remained high, hydrocortisone was replaced by an oral dexamethasone treatment of 0.5 mg/day, followed by the normalization of serum progesterone. A thawed blastocyst was transferred after preparation with oral estradiol at 6 mg/day and intravaginal progesterone at 600 mg/day under continuous suppression of endogenous progesterone production with a gonadotropin-releasing hormone agonist and oral dexamethasone. The patient became pregnant and delivered two healthy girls at term. One year after delivery, the presence of 21-hydroxylase antibodies was detected, which might explain the particularities of adrenal steroids in our patient. Our case report demonstrates that a patient with 17OHD can become pregnant through IVF and the transfer of thawed embryos in a subsequent cycle under continuous suppression of adrenal and ovarian progesterone production.

An Approach to Traumatic Brain Injury-Related Hypopituitarism: Overcoming the Pediatric Challenges.

Traumatic brain injury (TBI)-related hypopituitarism is a rare polymorphic complication of brain injury, with very little data, particularly concerning children and teenagers. This is a comprehensive review of the literature regarding this pathology, starting from a new pediatric case. The research was conducted on PubMed and included publications from the last 22 years. We identified nine original studies on the pediatric population (two case reports and seven studies; only four of these seven were prospective studies). TBI-related hypopituitarism is associated with isolated hormonal deficits ranging from 22.5% to 86% and multiple hormonal deficiencies from 5.9% to 50% in the studied pediatric population. Growth hormone (GH) deficiency is most often found, including the form with late occurrence after TBI; it was described as persistent in half of the studies. Thyroid-stimulating hormone (TSH) deficiency is identified as a distant complication following TBI; in all three studies, we identified this complication was found to be permanent. Adrenocorticotropic hormone (ACTH) deficiency did not relate to a certain type of brain trauma, and it was transient in reported cases. Hyperprolactinemia was the most frequent hormonal finding, also occurring late after injury. Central diabetes insipidus was encountered early post-TBI, typically with a transient pattern and did not relate to a particular type of injury. TBI-related hypopituitarism, although rare in children, should be taken into consideration even after a long time since the trauma. A multidisciplinary approach is needed if the patient is to safely overcome any acute condition.

Psycho-Emotional Impact of Anomaly Ultrasound Scan in Romanian Pregnant Women.

OBJECTIVE: Second-trimester anomaly scan was introduced as a regulated practice in Romania in 2019, causing misperceptions and unrealistic expectations about this examination among pregnant women. This study aimed to assess whether second trimester anomaly scan is a reason "per se" for maternal anxiety. DESIGN: A prospective type 1 cohort study was conducted in a tertiary prenatal diagnosis center with three locations in Bucharest, Romania, among pregnant women who underwent a second trimester anomaly scan between 1 December 2019 and 29 February 2020. MAIN OUTCOME MEASURE: Anxiety at the time of prenatal anomaly scan. RESULTS: Out of the 138 participants, 32.6% believed that the anomaly scan could detect all fetus defects, 13.8% considered that the baby is bothered by the probe "light", 8.7% believed that the scan could harm the fetus, 96.4% reported that it was a pleasant experience, and 95% felt that it strengthened their bond with the fetus. The State-Trait Anxiety Inventory (STAI) score revealed that women with high state anxiety were more anxious at pre-scan (p = 0.001). CONCLUSION: Ultrasound scan in the second trimester is correlated with a significant anxiety for women who are prone to this psychological trait. It is also a good opportunity to screen for highly anxious women who could benefit from prenatal psychological counseling to facilitate timely recognition and prevention of postpartum psychiatric disorders such as depression.

Social Freezing: Pressing Pause on Fertility.

Increasing numbers of women are undergoing oocyte or tissue cryopreservation for medical or social reasons to increase their chances of having genetic children. Social egg freezing (SEF) allows women to preserve their fertility in anticipation of age-related fertility decline and ineffective fertility treatments at older ages. The purpose of this study was to summarize recent findings focusing on the challenges of elective egg freezing. We performed a systematic literature review on social egg freezing published during the last ten years. From the systematically screened literature, we identified and analyzed five main topics of interest during the last decade: (a) different fertility preservation techniques, (b) safety of freezing, (c) usage rate of frozen oocytes, (d) ethical considerations, and (e) cost-effectiveness of SEF. Fertility can be preserved for non-medical reasons through oocyte, embryos, or ovarian tissue cryopreservation, with oocyte vitrification being a new and optimal approach. Elective oocyte cryopreservation is better accepted, supports social gender equality, and enhances women's reproductive autonomy. Despite controversies, planned oocyte cryopreservation appears as a chosen strategy against age-related infertility and may allow women to feel that they are more socially, psychologically, and financially stable before motherhood.

The ratio of exogenous Luteinizing hormone to Follicle stimulating hormone administered for controlled ovarian stimulation is associated with oocytes' number and competence.

We performed a retrospective study aiming to study the relationship between the ratio of the exogenous luteinizing hormone to follicle stimulating hormone (LH/FSH) administrated for controlled ovarian stimulation (COS) and the number and competence of the oocytes retrieved for in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Eight hundred sixty-eight consecutive infertile patients (mean age 34.54 ± 4.01 years, mean anti-Müllerian hormone (AMH) 2.94 ± 2.07 ng/ml) treated with long agonist protocol and a mixed gonadotropin protocol (human menopausal gonadotropin in association with recombinant FSH (recFSH)) who performed IVF/ICSI between January 2013 and February 2016, were included. Patients with severe male factor were excluded. LH/FSH was calculated based on total doses of the two gonadotropins. We found, after adjustment for confounders, a positive relationship between LH/FSH and the retrieved oocytes' (ß = 0.229, P<0.0001) and zygotes' number (ß = 0.144, P<0.0001) in the entire study group and in subgroups according to age (<35 and ≥35 years) and ovarian reserve (AMH < 1.1 and ≥ 1.1 ng/ml). The fertilization rate was positively associated with LH/FSH in patients with LH/FSH in the lowest three quartiles (below 0.77) (ß = 0.096, P=0.034). However, patients in the fourth quartile of LH/FSH had a lower fertilization rate as compared with patients in quartiles 1-3 which, after adjustment for covariates, was only marginally negatively related with LH/FSH (ß = -0.108, P=0.05). In conclusion, our results suggest that the adequate LH/FSH administrated during COS can improve the oocytes' and zygotes' number in IVF/ICSI cycles, but also the fertilization rate when a certain proportion of LH/FSH is not exceeded.

The relationship between anti-Müllerian hormone serum level and body mass index in a large cohort of infertile patients.

PURPOSE: To evaluate the relationship between serum Anti-Müllerian hormone (AMH) level and body mass index (BMI) in infertile patients. METHODS: Medical records of patients with infertility evaluated between January 2013 and February 2018 in the Reproductive Medicine Department of a private hospital were reviewed. Patients with the following criteria were excluded from the study: polycystic ovary syndrome, primary ovarian insufficiency, AMH values > 10 ng/mL, current oral contraceptive users and previous ovarian surgery or endometriosis, and anovulation of other causes, except decreased ovarian reserve. RESULTS: A total of 2204 infertile patients were included (mean age 34.58 ± 4.3 years, mean BMI 22.35 ± 3.6 kg/m2, and mean serum AMH 2.44 ± 2.17 ng/ml). In the entire group of patients, serum AMH level was positively correlated with BMI after adjustment for age (beta = 0.059, p < 0.005). When the association between serum AMH level and BMI was analysed in subgroups of patients, after adjustment for age, we found a positive correlation between the two parameters in patients ≤ 35 years old (< 0.05), of normal weight (p < 0.05) and with normal ovarian reserve (p < 0.05). After adjustment for age, BMI ≥ 25 kg/m2 was significantly associated with higher AMH values in comparison to normal weight patients. CONCLUSIONS: In infertile patients, AMH is positively correlated with BMI, especially in patients younger than 35 years, of normal weight and with normal ovarian reserve. Moreover, the presence of mild excess adiposity seems to be associated with higher AMH values. Our data contradict the previous studies showing a negative impact of excess adiposity on AMH serum levels.

Is growth hormone administration essential for in vitro fertilization treatment of female patients with growth hormone deficiency?

Available evidence suggests that the fertility of growth hormone deficient female patients could be decreased, although the responsible mechanisms are unknown. Taking into account the multiple effects of growth hormone on reproduction suggested by experimental and clinical studies in women without growth hormone deficiency, the growth hormone deficit by itself could contribute to infertility in these patients. However, the necessity of growth hormone administration and the profile of the infertile patients with growth hormone deficiency who would benefit from treatment are largely unknown. Growth hormone effects on oocyte quality is one of the possible mechanisms through which growth hormone could be involved in fertility of these patients. However, this hypothesis was not tested in patients with adequately diagnosed growth hormone deficiency. We present the case of a 29-year-old female patient with growth hormone deficiency and tubal infertility who was referred for in vitro fertilization treatment. The couple underwent two conventional in vitro fertilization procedures: the first one, without growth hormone treatment and, because no pregnancy was achieved, the second one after growth hormone (somatropinum) administration for 3 months. Although the number of the retrieved oocytes was the same, the quality of the oocytes was improved and their ability to evolve into good quality embryos after fertilization was increased after growth hormone administration. Consequently, the pregnancy was obtained after the second in vitro fertilization treatment and patient gave birth to a healthy boy. In conclusion, our case report suggests that adequate levels of growth hormone are essential for an adequate competence of the oocytes in infertile patients with growth hormone deficiency. Therefore, growth hormone administration should be taken into consideration for patients with this deficiency in order to optimize the results of infertility treatment. Abbreviations: GH: growth hormone; GHD: growth hormone deficiency; HCG: human chorionic gonadotropin; IVF: in vitro fertilization; IGF: insulin like growth factor.

Cell free fetal DNA testing in maternal blood of Romanian pregnant women.

BACKGROUND: The discovery of circulating fetal DNA in maternal blood led to the discovery of new strategies to perform noninvasive testing for prenatal diagnosis. OBJECTIVE: The purpose of the study was to detect fetal aneuploidy at chromosomes 13, 18, 21, X, and Y by analysis of fetal cell-free DNA from maternal blood, without endangering pregnancy. MATERIALS AND METHODS: This retrospective study has been performed in Bucharest at Medlife Maternal and Fetal Medicine Department between 2013-2014. In total 201 women were offered noninvasive prenatal test. Maternal plasma samples were collected from women at greater than 9 weeks of gestation after informed consent and genetics counseling. RESULTS: From 201 patients; 28 (13.93%) had screening test with high risk for trisomy 21, 116 (57.71%) had advanced maternal age, 1 (0.49%) had second trimester ultrasound markers and the remaining 56 patients (27.86%) performed the test on request. Of those patients, 189 (94.02%) had a "low risk" result (<1/10,000). Of those who had a low risk result, 2 continued on to have amniocentesis with normal results.Five patients (2.48%) received "high risk" results (>99% risk) all for trisomy 21 (T21). T21 was confirmed by amniocentesis in 1 patient and the other 4 patients declined confirmation. The 7 remaining patients (3.48%) had a low fetal fraction of DNA. CONCLUSION: It is probably that prenatal diagnosis using fetal DNA in maternal blood would play an increasingly role in the future practice of prenatal testing because of high accuracy.