Dragos Albu

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.

Hyperprolactinemia is a known cause of amenorrhea and infertility. However, there is an increasing body of evidence suggesting that prolactin is involved in multiple physiological aspects of normal reproduction. Thus, the present paper aims to review the current literature regarding the relationship between serum prolactin level and in vitro fertilization (IVF)/intracytoplasmic sperm injection outcome and the role of dopamine agonists treatment in IVF success. Moreover, the mechanisms by which prolactin may exert its role in fertility and infertility were summarized. Although not all studies agree, the available evidence suggests that higher prolactin levels in follicular fluid are associated with increased oocytes competence, but also with positive effects on corpus luteum formation and survival, endometrial receptivity, blastocyst implantation potential and survival of low-motile sperm. Transient hyperprolactinemia found in IVF cycles was reported in most of the studies not to be related to IVF outcome, although a few reports suggested that it may be associated with higher implantation and pregnancy rates, and better-cumulated pregnancy outcomes. Administration of dopamine agonists for hyperprolactinemia preceding IVF treatment does not seem to negatively impact the IVF results, while treatment of transient hyperprolactinemia during IVF might be beneficial in terms of fertilization rates and conception rates. Due to limited available evidence, future studies are necessary to clarify the optimal level of circulating prolactin in patients performing IVF and the role of dopamine agonist treatment.

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.

Cornelia de Lange syndrome is a developmental disorder with a great degree of clinical and genetical variability characterized by typical facial features, growth impairment and multi-organ anomalies. It is caused by mutations in the cohesin complex that is involved in regulation of gene expression. Growth disturbances are a major feature of the syndrome and have various underlying mechanisms. Other associations regarding endocrine function are represented by disturbances in the hypothalamic-pituitary axis, decreased bone density associated with fractures and genital malformations associated with menstrual irregularities and altered fertility.

Endometriosis, a frequent condition in reproductive age women, is also associated with infertility by mechanisms incompletely clarified. The effectiveness of endometriosis treatment for infertility is debated, being possible that in vitro fertilization (IVF) offers a better alternative. The response to controlled ovarian stimulation (COS) is an important predictor of live birth, but it might be affected in endometriosis possibly through a decrease of ovarian reserve. Moreover, the predictive value of anti-mullerian hormone (AMH) for the response to COS could be altered by factors disrupting the AMH production in endometriosis. Therefore, we aim to review the literature regarding the response to COS and the AMH production and their predictive value for COS response in patients with endometriosis.

Polycystic ovary syndrome (PCOS) is a frequent disorder affecting women of reproductive age characterized by infertility. Affected endometrial receptivity seems to contribute to decreased fertility of these patients as suggested by several studies. Understanding the mechanism behind this reduced endometrial receptivity could contribute to discovery of new therapeutic targets for infertility of PCOS. The aim of the paper is to review the current data regarding endometrial receptivity in PCOS patients, the potential mechanisms involved with particular focus on recent findings as the impact of gut microbiota on endometrium, the relationship between vitamin D and endometrial receptivity and the different impact of letrozole and clomiphene citrate on endometrial receptivity in infertile PCOS 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.

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.

Beta thalassemia is the most frequent hemoglobinopathy worldwide. In patients with beta thalassemia major (BTM), the consequence of long-term life-saving transfusions is iron overload in liver, heart and endocrine glands. Hypogonadotropic hypogonadism is the most frequent endocrine complication. Recent progresses in the treatment of BTM dramatically improved life expectancy and quality of life of these patients, making the concern for fertility and pregnancy to gain importance. Therefore, we performed a review of the available data regarding hypogonadism in female patients with BTM. We found that hypogonadotropic hypogonadism is still frequently found in female patients with BTM. Pituitary iron overload seems to be the main factor contributing to hypogonadism occurrence, although iron-related damage of the ovaries and the genital tract cannot be excluded. The increased oxidative stress observed in BTM patients was hypothesized as a contributor to pituitary-gonadal dysfunction. Hypogonadism has significant consequences on quality of life, final height, bone health and fertility of the patients. Estro-progestative administration is essential in order to minimize consequences, although the best treatment regimen should be carefully weighted in each patient. Although spontaneous fertility is reduced by the presence of hypogonadism, it seems that ovulation-induction treatment with gonadotropins is effective in achieving pregnancies in majority of patients.

The increasing age seems to have a negative impact on reproductive functions not only in women but also in men. Therefore, our aim was to review the data available in the literature regarding the impact of advancing age on fertility and the mechanisms underlying this association in both genders. The available data suggest that the effects of age on ovarian function cause a decrease in fertility starting 13 years before menopause. Statistics show that 10% of women will have a decreased fertility starting with the age of 30. The impact of age on ovary is due to both decreased number and quality of the oocytes, resulting in a high rate of chromosomal aneuploidy in the embryo and mitochondria dysfunction. Assisted reproductive technologies aiming to identify competent embryo were created but for the moment the results are unsatisfactory. On the other hand, in men, the semen quality and testicular function were found to gradually decrease with age and most of the studies also describe a negative impact on fertility. The mechanisms underlying decreased fertility are mainly genetic and epigenetics changes. However, if the effects of age on male fertility in men can be overcome by assisted reproductive technologies is not clear yet as the results of the studies are inconsistent.