Hyperthyroidism secondary to a hydatidiform mole.

The case presented in the article is that of a 47-year-old female patient with hyperthyroidism induced by a hydatidiform mole. Attention was drawn to the necessity of preparing the patient for a procedure with drugs that stabilize the hormonal activity of the thyroid. The removal of the hydatidiform mole resulted in gradual normalization of thyroid hormone levels. The trophoblast has a hormonal activity, secrete hCG (human chorionic gonadotropin).The hCG partial structural homology causes affinity to the TSH (thyroid stimulating hormone) receptor. The higher the weight of the trophoblast, the higher the production and concentration of hCG in the blood. Therefore, gestational trophoblastic disease may be accompanied by hyperthyroidism. The problem is frequently described, however, due to the risk of developing thyroid storm, it cannot be overlooked [1].

TMD in Females with Menstrual Disorders.

BACKGROUND: Temporomandibular disorders (TMD) are a common reason for patients to present at dental offices. The majority of people with TMD are women between the age of 20 and 40 years. The purpose of this study was to assess the types and prevalence of temporomandibular disorders in female patients of reproductive age with menstrual disorders. MATERIALS AND METHODS: The study involved 65 females of reproductive age (18-40 years, an average of 28.00 ± 6.27 years). The women who qualified for the study were patients of the University Center for Maternal and Newborn's Health hospitalized because of infertility or menstrual cycle disorders. Women with confirmed estrogen metabolism disorders participated in a clinical study with the use of Diagnostic Criteria for Temporomandibular Disorders (DC/TMD). RESULTS: In the studied female patients with menstrual disorders, temporomandibular disorders (92.3%) were frequent occurrences. The most common type was intra-articular joint disorders (68%). Other reported complaints included masticatory muscle pain (44.62%), and degenerative joint diseases (12.3%). CONCLUSIONS: 1. In women with menstrual disorders, TMD may exist. 2. In women with TMD symptoms, their medical history should be extended to include the diagnosis of female hormone disorders.

Premature ovarian insufficiency as a variable feature of blepharophimosis, ptosis, and epicanthus inversus syndrome associated with c.223C > T p.(Leu75Phe) FOXL2 mutation: a case report.

BACKGROUND: FOXL2 gene mutations cause blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) and may be associated with premature ovarian insufficiency (POI). Two types of BPES were described in the literature. BPES type 2 is a simple association of inherited developmental defects of the eyelid area, while in type 1 female patients additionally suffer from POI. The following case study is the first report of endocrine impairments typical for menopausal transition in young female with NG_012454.1:g.138665342G > A, c.223C > T p.(Leu75Phe), mutation in FOXL2 gene. This mutation has been reported in the literature before, however until now, it was never linked to BPES type 1. CASE PRESENTATION: An 18-year-old nulliparous woman suspected of secondary amenorrhea was referred to our Endocrinology Outpatient Clinic. Blood tests revealed decreased levels of AMH (anti-Mullerian hormone) and increased levels of gonadotropins, suggesting menopausal transition. Her past medical history was remarkable for several ophthalmic defects that has required surgical interventions. BPES syndrome had not been suspected before, although the patient had reported a similar phenotype occurring in her father, sister and half-sister. Venous blood samples were collected from the female proband and from her three family members. Whole-exome sequencing and deep amplicon sequencing were performed. A potential pathogenic variant in the FOXL2 gene was revealed. Namely, the c.223C > T p.(Leu75Phe) missense variant was detected. CONCLUSIONS: The authors found mutations, c.223C > T p.(Leu75Phe) in the FOXL2 gene in a young woman with hormonal disorders suggesting menopausal transition. These results indicate that the possibility of different phenotypes should be considered in patients with a similar genetic mutation.

The association between serum metalloproteinase concentration, obesity, and hormone levels in reproductive-aged women.

INTRODUCTION: Increased levels and activity of some matrix metalloproteinases (MMPs) are described in obesity-related vascular diseases. Factors that influence MMP blood concentration are still being investigated. This research aims to evaluate the concentration of most types of MMPs: collagenases (MMP-1, -3, -8, -13), matrilysin (MMP-7), gelatinase (MMP-9), and metalloelastase (MMP-12) in serum of women in reproductive age in relation with their body mass index (BMI), age, oestradiol, and progesterone concentrations. MATERIAL AND METHODS: Blood samples were taken from 54 healthy reproductive-aged women with normal menstrual cycles. The weight and height of all women were measured, and body mass index (BMI) was calculated. Concentration of MMP-1, -3, -7, -8, -9, -12, and MMP-13 was evaluated using a Procarta Immunoassay Kit. Serum concentrations of oestradiol and progesterone were evaluated by immunochemiluminescence (32 in the proliferative and 20 in the secretory phase of menstrual cycle). The results of the study were statistically calculated using Pearson, Spearman, and Kruskal-Wallis tests. RESULTS: Positive correlation between MMP-7, -8, -9, -12, and -13 levels and BMI was demonstrated. Significantly higher concentrations of MMPs were found especially in obese women compared to women with normal BMI. In healthy, regularly menstruating premenopausal women, MMP levels did not correlate with oestradiol and progesterone concentrations. CONCLUSIONS: The results suggest that body mass can influence MMP serum concentration in women with regular menstrual cycles.

25(OH)D serum concentration in women with menstrual disorders -risk factors for Vitamin D deficiency.

INTRODUCTION: Vitamin D (VD) plays a crucial role in calcium metabolism as well as immunological and endocrine homeostasis. Previous studies revealed strong inverse correlation between VD levels and insulin resistance, parathyroid dysfunctions and autoimmune thyroid disease. Insufficient evidence concerns its dependency of ovarian hormones. Malfunctioning of the ovaries results in menstrual disorders that are one of the most common endocrine impairments in young women of reproductive age. MATERIAL AND METHODS: The study was aimed to evaluate the correlation between 25(OH)D serum concentration and estradiol, testosterone as well as body mass index (BMI) in women with oligomenorrhea. 134 women of reproductive age with oligomenorrhea were eligible for the study. 25-hydroxyvitamin D [25(OH)D], estradiol, testosterone and sex hormone-binding globulin (SHBG) were measured using chemiluminescence immunoassay. Free androgen index (FAI) and body mass index (BMI) were calculated. RESULTS: Critical 25(OH)D deficiency (<10 ng/ml) was found in 13.4% of women, the risk of deficiency (<30 mg/dl) was diagnosed in 69.4%, while sufficient level of VD (>30 mg/ml) in 17.2% of them. Significant negative correlation was detected between 25(OH)D and estradiol serum concentrations (r=-0.2; p=0.049), as well as BMI levels (r=-0.22; p=0.01). However, no significant correlation was found between 25(OH)D and testosterone (r=-017; p=0.055), SHBG (r=0.08; p=0.4) and FAI (r=-0.1; p=0.24). CONCLUSIONS: Thorough assessment of vitamin D deficiency/insufficiency is required among patients with menstrual disorders, especially those overweighed and obese. Early screening and VD supplementation in women with estrogen-dependent disorders may become a part of routine management in order to optimize endocrine health.

Matrix metalloproteinases-2, -7 and tissue metalloproteinase inhibitor-1 expression in human endometrium.

INTRODUCTION: Endometrium undergoes regular, cyclic tissue remodeling mostly associated to the endocrine system status. It is well-known fact that steroid hormones are strongly responsible for changes in endometrium. The precise mechanism of their action is still under investigation. The aim of the study was to evaluate the expression of metalloproteinases 2 and 7 (MMP-2, -7) and tissue inhibitor of metalloproteinase 1 (TIMP-1) in human endometrium in relation to serum concentrations of estradiol and progesterone during different phases of menstrual cycle. MATERIAL AND METHODS: The study material consisted of 52 biopsy samples; 12 obtained in the proliferative phase, 11 in the secretory phase and 29 during menstruation. Expression of MMP-2, MMP-7 and TIMP-1 was assessed by immunohistochemistry. Serum concentrations of estradiol and progesterone at time of biopsy were evaluated by immunochemistry assay. Results of the study were statistically assessed by linear regression model. RESULTS: Increased serum concentration of estradiol was associated with increased MMP-2 expression in proliferative phase but decreased in secretory phase and during menstruation. No significant relationship was found between progesterone concentration and MMP-2 expression. Moreover, no difference in the expression of MMP-7 and TIMP-1 in the endometrium in relation to hormone levels and menstrual cycle phases were observed. CONCLUSIONS: The results of the study indicate that estradiol influence MMP-2 expression in the endometrium depends on the phase of menstrual cycle. Such relationships were not found for MMP-7 and TIMP-1 and further tests clarifying association between estradiol and MMPs are needed.

The role of lifestyle changes in the treatment of polycystic ovary syndrome.

Polycystic ovary syndrome is one of the most common endocrinopathy of the reproductive age. Heterogenity of its clinical symptoms is related to the presence of a number of phenotypes of this disfunction, hence the necessity for individualized treatment is needed. A change of a lifestyle, well-balanced diet and physical activity are the most effective medical way contributing to the improvement of carbohydrate metabolism parameters and weight reduction which reactivates regular ovulation and facilitates getting pregnant. A change of diet should encompass determination for appropriate calorie requirements, content of particular macroelements as well as selection of the products with low glycemic index. Vitamin D supplemantation as well as inosital is of great importance as well. Both these ingredients are extremely effective in treating the disorders resulting from polycystic ovary syndrome. Adding them to a daily diet contributes to improving carbohydrate metabolism and reducing insulin resistance. Additionally, they accelerate weight loss, regulate menstrual cycles and enhance reinstating regular ovulation, hence facilitate to get pregnant. Together with introducing dietary changes, patients should be reminded about the crucial role of physical activity. A kind of exercises should be chosen according to a patient's preferences and be adjusted to her actual health condition. Only physical activity done with pleasure may become a healthy custom improving the effects of a proper diet.

Expression of matrix metalloproteinase enzymes in endometrium of women with abnormal uterine bleeding.

OBJECTIVES: Abnormal uterine bleeding (AUB) is caused by derangement of physiological processes of tissue growth, shedding and regeneration. It is known that interplay between metalloproteinases (MMP's) and tissue inhibitors of metalloproteinases (TIMP's) may play a crucial role in its occurrence. AIM: To define if expression of proMMP-2, MMP-2 and TIMP-1 in endometrium of women with AUB is dependent on steroid sex hormone concentration and histopathological picture. MATERIALS AND METHODS: Endometrial scraps were taken from 21 women with AUB and 19 controls. Samples were evaluated in light microscopy by a certified pathologist. Activity of proMMP-2 and MMP-2 proteins levels were evaluated by gelatin zymography and TIMP-1 by reversed zymography. The results has been correlated with serum estradiol and progesterone concentrations in linear regression model. RESULTS: Expression: of proMMP-2 in endometrium of women with AUB is correlated with estradiol concentration and inversely correlated with progesterone levels. It was significantly higher in women with dysfunctional endometrium (p<0.001). Expression of MMP-2 was highest in women with endometrial polyps and longer bleeding (p<0.01), while expression of TIMP-1 was independent from hormone concentration. CONCLUSION: Lack of correlation between proMMP-2 and MMP-2 levels suggest different pathway of their activation in AUB. ProMMP-2 is up regulated by estradiol and down regulated by progesterone while MMP-2 levels increase with the length of bleeding.

The role of metalloproteinases in endometrial remodelling during menstrual cycle.

Endometrium is the only tissue in the human body subject to cyclic transformations under the influence of ovarian steroid hormones. As estradiol and progesterone balance throughout the physiological menstrual cycle changes, so does the expression of metalloproteinases (MMPs). These endopeptides are responsible for keeping the balance between the process of synthesis and degradation of extracellular matrix proteins. Thus, MMP's take part in sustaining physiological stability of the endometrium. A number of MMPs found in the endometrial tissue and their activity is related to menstrual cycle phase. This paper is an up-to-date review of literature of Medline database. The search was conducted for key words including "matrix metalloproteinases", "MMPs", "TIMPs" and "tissue inhibitors of metalloproteinases". Over 1092 publications regarding interdependence and interplay between ovarian hormones and the role of various MMPs and their inhibitors in normal endometrial remodelling and in pathological conditions were analysed and critically reviewed.

Fetal Hypotrophy Is an Important Marker in Diagnosis of Preeclampsia in Pregnant Patients After Solid Organ Transplantation.

BACKGROUND The purpose of this study was to use a multidisciplinary approach to define the importance of fetal growth disturbances in pregnant patients after renal or liver transplantation in diagnosis and treatment of preeclampsia. MATERIAL AND METHODS We assessed 108 pregnancies in patients with renal or liver transplants. Statistical analysis included Pearson's chi-square test and Fisher's exact test. RESULTS In the renal transplant (RTR) group, preeclampsia was diagnosed in 40% according to ISSHP. In the liver transplant (LTR) group, ISSHP guidelines allow this diagnose in 14.6% of patients. Intrauterine fetal hypotrophy occurred in 53.3% of RTR patients with clinical symptoms of preeclampsia and in none of stabile patients. Premature delivery rate was 40% in patients with hypotrophy and only in 15.5% without. For LTR patients, hypotrophy was diagnosed in 16.4% patients with clinical symptoms of preeclampsia and in 12.7% of stabile patients. Premature delivery rate was 14.5% in patients with hypotrophy and in 14.5% without. CONCLUSIONS Fetal hypotrophy is strongly associated with premature delivery and risk of preeclampsia in pregnancies after renal transplantation. There is a need for including ultrasound findings in diagnostic criteria of preeclampsia. Fetal growth monitoring may help in prediction of premature delivery in these group.

Anxiety and depression in women undergoing infertility treatment.

Infertility is a significant problem for millions of couples. Recently more attention is being paid to the relationship between infertility treatment with the use of Assisted Reproductive Techniques and the presence of mental disturbances, of which anxiety and depression are the most common. We present a review of recent studies evaluating the influence of anxiety and depression on fertility treatment outcomes and the effect of Assisted Reproductive Techniques treatment on the presence of anxiety and depression among women. The studies show conflicting results concerning the effect of anxiety on Assisted Reproductive Techniques treatment outcomes, but most reveal that Assisted Reproductive Techniques treatment leads to an increased level of anxiety, especially in cases of treatment failure and longer durations of treatment. Most studies do not show a relationship between depression and Assisted Reproductive Techniques treatment outcomes, but it seems that severe depression can lead to lower rates of pregnancy during infertility treatment with Assisted Reproductive Techniques. Moreover, women who become pregnant after Assisted Reproductive Techniques treatment seem to have an increased risk of depression in later life.

Intrauterine growth restriction in pregnant women after kidney transplantation as a marker of preeclampsia.

OBJECTIVES: Delayed motherhood is associated with an increasing number of comorbidities such as glomerulonephritis, systemic lupus erythematosus, and diabetic nephropathy. Women after renal transplant belong to the group of patients who require a highly individualized approach to treatment and diagnosis. The aim of the study was to validate the commonly used diagnostic criteria for preeclampsia which seem to be irrelevant in patients with chronic renal insufficiency. MATERIAL AND METHODS: The course of pregnancy and delivery were retrospectively analyzed in 48 renal transplant patients. Two patients were excluded. Group I included 23 patients with eutrophic neonates, while Group II consisted of 23 patients with fetal hypotrophy (birth weight of < 10th percentile). RESULTS: The duration of pregnancy was 34.5 and 35 weeks in Groups I and II, respectively. Mean birth weight in Groups I and II was 2608.64 g and 2046.30 g, respectively (p = 0.002). Mean weight percentile in Groups I and II was 36.57 and 2.91, respectively (p < 0.000). Proteinuria in the first half of pregnancy occurred in 16 and 14 patients from Groups I and II, respectively, and increased in the second half of pregnancy in 6 and 6 patients from Groups I and II, respectively. Patients from Group II were more prone to urinary tract infections (0.43 vs. 0.79; p = 0.02). CONCLUSIONS: Current diagnostic criteria for preeclampsia are insufficient in case of pregnant women after kidney transplant. General criteria should be applied with special care in women with chronic kidney disease or in patients with systemic lupus erythematosus. As a predictive factor of neonatal morbidity, intrauterine growth restriction seems to be more valuable than typical markers of kidney function.

Menopause in women with chronic immunosuppressive treatment - how to help those patients.

Women after organ transplantation with chronic immunosuppressive therapy or after bone marrow transplantation without such therapy are a growing group of patients. Although their problems in the peri- and postmenopausal period are the same as in healthy women, due to the primary disease and treatment applied they represent a huge challenge from the point of view of their hormonal treatment of menopause. Transplanted women have no particular contraindications for hormonal therapy use. General contraindications, however, such as arterial hypertension, thrombosis in medical history, diabetes, endometriosis, myomas, or active neoplastic disease, have a higher incidence in this group of patients than in healthy women, which significantly influences the possibility of using hormonal therapy. On the other hand, taking into consideration the predisposition for premature menopause in this group, in combination with chronic immunosuppression, it predisposes these patients for higher cardiovascular disease incidence and bone density loss, so hormonal therapy would be highly advisable. Therapy management in transplanted patients requires special care and close monitoring of the transplanted organ. Saving lives with organ transplantation is one of the greatest achievements of contemporary medicine. For long-term improvement of their quality of life, emphasis should be put on regular diagnostic examinations, early detection of abnormalities, and introduction of effective treatment.

Activity of Proteolytic Enzymes and Level of Cystatin C in the Peripartum Period.

Objectives. The aim of the study was to evaluate the activity of cathepsin B, collagenases, trypsin, and plasmin and concentration of cystatin C in serum of healthy pregnant women in peripartum period. Study Design. The study group included 45 women in uncomplicated pregnancies. Blood samples were collected in four time points. Enzyme activity was measured by spectrofluorometric method. The level of cystatin C was measured using immunonephelometric method. Results. Mean activity of cathepsin B and the level of serum cystatin C were significantly higher in the study group. Collagenase activity was significantly lower in the study group than the control group. No differences in collagenase, plasmin, and trypsin activity on each day of the peripartum period were found. Conclusion. High activity of cathepsin B and increased level of cystatin C are typical for women in late pregnancy. Those levels significantly decrease after delivery which can be associated with potential role of those markers in placental separation. The insignificant changes of cystatin C level in the peripartum period seem to exclude the possibility of using cystatin C as a marker for renal insufficiency in the peripartum period but additional research is necessary to investigate the matter further.

Endometrial injury for women with previous in vitro fertilization failure - does it improve pregnancy rate?

Implantation failure is one of the major factors limiting success of in vitro fertilization (IVF) treatment. According to ESHRE 2009 data only 32% of fresh embryo transfers resulted in clinical pregnancies. There are many ideas to improve the treatment outcomes, endometrial injury being one of them. It has been suggested that local endometrial injury, performed either by pipelle biopsy or hysteroscopy, may increase clinical pregnancy rate. However, up to date literature is widely disparate on that subject. There is no conclusion with regard to optimal timing, the number and technique of the procedure. The following paper is the review of the evidence from clinical studies dealing with the effect of endometrial injury on the IVF outcome to guide clinical practice for this challenging problem. PubMed, Embase, the Cochrane Library using Medical Subject Headings and free text terms were searched up to June 2016 without year restriction. Though the majority of trials showed positive impact of endometrial injury on IVF outcome, there is still a lack of strong evidence to support routine local endometrial injury in women prior to IVF treatment.

Gestational diabetes insipidus. Case Report.

Gestational diabetes insipidus is a very rare complication. However, undiagnosed and untreated may lead to serious complications in both mother and fetus. In this study, a case of 34-year-old female patient with diabetes insipidus associated with pregnancy was reported. We discussed process of diagnosis and treatment with particular emphasis on the monitoring of water-electrolyte imbalance during labor.

Non trophoblastic source of human chorionic gonadotropin - problem in diagnostic accuracy.

Human chorionic gonadotropin (hCG) is a polypeptide hormone studied as far as 1912, but researchers has no complete knowledge concerning its biological function. Since 1970' it is known that hCG can be found not only in the urine and serum of pregnant, but in choriocarcinoma and testicular cancer patients. Up-to-date one can distinguish four subtypes of hCG differing in secondary carbohydrate chains configuration as well as it regular and glycosylated forms, but non trophoblastic sources of this hormone, such as pituitary are still not widely known. The article gives an overlook on hCG studies in order to help clinicians in taking wise, evidence based decisions in asymptomatic patients with elevated hCG.

Successful Pregnancy Outcome after In Vitro Fertilization in a Kidney Graft Recipient: A Case Report and Literature Review.

BACKGROUND: Successful spontaneous pregnancy in a kidney graft recipient is regarded as a sign of full recovery. The crucial factors determining positive outcome are optimizing time of conception and multidisciplinary team care. However, there are only a few reports dealing with in vitro fertilization (IVF) outcomes in organ recipients. CASE REPORT: A 34-year-old living donor kidney recipient with primary infertility due to bilateral tubal obstruction was referred to our clinic. Transfer of 2 embryos was conducted after a long stimulation protocol with GnRH and rFSH, and a viable singleton pregnancy was confirmed by subsequent ultrasound examination. Pregnancy complications were: chronic hypertension, fetal intrauterine growth restriction, and severe anemia requiring blood transfusions and erythropoietin treatment. In the 34th week of gestation the patient presented with worsening of blood pressure control. A male newborn, 1810 grams weight and 10 points Apgar score was delivered by cesarean section. Although our patient was qualified for the IVF program with signs of suboptimal graft function, it was stable during the ovarian stimulation protocol. Fortunately, in the second half of the pregnancy only mild creatinine rise and proteinuria <1 g/day were observed. CONCLUSIONS: IVF may be a good treatment option in female kidney graft recipients. It does not necessarily lead to graft function deterioration and it provides multidisciplinary specialized care, allowing for delivery of a healthy newborn.

The role of vitamin D in reproductive health--a Trojan Horse or the Golden Fleece?

In the last decade, vitamin D was in the spotlight in many fields of research. Despite numerous publications, its influence on reproductive health remains ambiguous. This paper presents an up-to-date review of current knowledge concerning the role of cholecalciferol in human reproduction. It covers various infertility issues, such as polycystic ovary syndrome, endometriosis, myoma-induced infertility, male infertility, premature ovary failure and in vitro fertilization techniques. Vitamin D deficiency, defined as serum concentration of 25-hydroxycalciferol of less than 50 nmol/L, is commonly noted more frequently than only in fertility clinic patients. It is a global trend that is observed in all age groups. The results of original publications dated up to 2015 have been summarized and discussed in a critical manner. Most experts agree that vitamin D supplementation is a necessity, particularly in women suffering from obesity, insulin resistance or small ovarian reserve, as well as in men with oligo- and asthenozoospermia if serum concentration should fall below 50 nmol/L (normal range up to 125 nmol/L). High concentration of vitamin D and its metabolites in decidua during the 1st trimester suggests its important role in the implantation process and a local immunological embryo-protection. On the other hand, evidence-based research did not prove a significant difference so far in ovulation stimulation or embryo development depending on vitamin D level. In one of the publications, it was also found that vitamin D binding protein (VDBP) has a molecular similarity to anti-sperm antibodies, and another one concluded that both low (<50 nmol/L) and high (>125 nmol/L) concentration of vitamin D are associated with decreased number and quality of spermatozoa in semen. Vitamin D is definitely not a Trojan Horse in reproductive health, since there were no adverse effects reported for vitamin D intake of up to 10,000 IU/day, but to proclaim it the Golden Fleece, more evidence is needed.

Factors influencing the severity of pain during hysterosalpingography.

OBJECTIVE: To analyze factors influencing the severity of pain during hysterosalpingography (HSG). METHODS: A prospective randomized study was performed among women with ongoing infertility undergoing HSG at a center in Poland between March and September 2013. The patients were assigned by random draw to receive 0.1g ketoprofen or 2.5g metamizole intravenously. Patients and physicians performing HSG were masked to assignment, but the healthcare workers who administered analgesics were not. Pain was assessed by a visual analogue scale (VAS) during and after the HSG procedure. RESULTS: A total of 80 women were assigned to ketoprofen and 89 were assigned to metamizole. There were no significant differences in VAS scores with regard to the administered analgesic, patient age, duration of infertility, medical history (previous delivery, abdominal surgery), or type of infertility. However, women who went on to have abnormal HSG results had higher VAS scores at time of contrast instillation and 30minutes after the procedure than did those who had confirmed bilateral patency of the tubes (P≤0.03 for both). CONCLUSION: An abnormal HSG result seems to be the main factor influencing the sensation of pain perceived by patients during the procedure.