Premature ovarian insufficiency - novel hormonal approaches in optimizing fertility.

Premature ovarian insufficiency (POI) is a delicate medical problem in young women. This condition is not unchangeable and permanent but is associated with intermittent and unpredictable ovarian activity, resulting in low conception rate. Over the period of 8 years, the evaluation of secondary amenorrhea was conducted in 90 patients below the age of 40 who wished to restore fertility. Having confirmed the diagnosis and investigated the etiology of POI, hormone replacement therapy was applied (sequential administration of estradiol and norethisterone acetate) in the first 30 patients (group A). Estrogen-progestogen therapy with daily supplementation of 25 mg of micronized oral dehydroepiandrosterone (DHEA) was conducted in 44 patients (group B), whereas a combined regime (estrogen-progestogen therapy, DHEA supplementation in daily dose of 25 mg, and melatonin supplementation in daily dose of 3 mg) was conducted in 16 patients (group C). In the course of our study, 16 pregnancies were realized (18% of all cases: 17% in group A; 18% in group B; 19% in group C) 6 to 20 months after the initiation of hormone therapy, and there have been 13 completed term pregnancies so far with normal fetal growth and development. We concluded that estrogen-progestogen therapy combined with DHEA and melatonin could optimize fertility and lead to successful pregnancy in POI patients.

Endometrium receptivity in premature ovarian insufficiency - how to improve fertility rate and predict diseases?

More empathized approach is required and is obligatory to women with premature ovarian insufficiency (POI) interested for pregnancy. In order to improve fertility rate in POI patients our suggestions would be: (1) To decrease FSH value to 10-15 IU/L by increasing estrogen. Oocyte donation can be suggested after a minimum of six month interval from FSH between 10-15 IU/L and when no dominant follicles are found. (2) To perform oral glucose tolerance test (OGTT). Insulin sensitizing agents has to be included, when indicated, 3-6 month before pregnancy. (3) TSH has to be 1-2.5 mM/L during 3-6 months before pregnancy. (4) Tests for thrombophyllia (Leiden V, FII, MTHFR, PAI) have to be obligatory. They are less expensive than those repeated in vitro fertilizations. Therapy has to be included according to the indications. (5) In order to regulate disturbed immune response in POI patients with endometriosis oral contraceptive therapy is needed for atleast six months prior to the pregnancy. (5) Encourage the patients and advice them about healthy life style and eating habits. (6) Add other drugs, when they are indicated. Complex interplay between endocrine, immunological, haematological, and psychological factors are very often underdetected in POI patients. It is very important to find out the real time for oocyte donation after correcting all the disturbances, improving endometrium receptivity and reaching women's acceptable psychological status. Untreated disturbances induce cardiovascular diseases, diabetes mellitus, thyroid diseases, coagulopathioes etc.

Melatonin: a "Higgs boson" in human reproduction.

As the Higgs boson could be a key to unlocking mysteries regarding our Universe, melatonin, a somewhat mysterious substance secreted by the pineal gland primarily at night, might be a crucial factor in regulating numerous processes in human reproduction. Melatonin is a powerful antioxidant which has an essential role in controlling several physiological reactions, as well as biological rhythms throughout human reproductive life. Melatonin, which is referred to as a hormone, but also as an autocoid, a chronobiotic, a hypnotic, an immunomodulator and a biological modifier, plays a crucial part in establishing homeostatic, neurohumoral balance and circadian rhythm in the body through synergic actions with other hormones and neuropeptides. This paper aims to analyze the effects of melatonin on the reproductive function, as well as to shed light on immunological and oncostatic properties of one of the most powerful hormones.

Hormone replacement therapy and successful pregnancy in a patient with premature ovarian failure.

Premature ovarian failure (POF), premature ovarian insufficiency, premature menopause or hypergonadotropic hypogonadism, a serious life-changing condition that affects young women, remains an enigma and the researcher's challenge. In the present article we described a case of singleton pregnancy in a 33-year-old patient, presenting with POF and treated with hormone replacement therapy. Twenty months later this therapy led to maturation of one follicle, recruitment and fertilisation of the residual oocyte and spontaneous pregnancy ensued. A normal infant was delivered by cesarean section.

Invasive mole--case report of massive uterine destruction.

Patient with malignant Gestational Trophoblastic Neoplasm (GTN) was treated by mean of MTX-FA, MAC, EMA-CO and EMA-EP. Changes in serum human chorionic gonadotropine (beta hCG) levels and changes in ultrasonographic findings were checked weekly. Finally transabdominal hysterectomy with ovaries conservation was done and polychemotherapy administrated after the operation until three consecutive serum chorionic gonadotropine values were negative. This is a case report of Invasive mole in 32 years old patient without possibility to preserve reproductive health. GTN developed two months after spontaneous abortion in 13th week gestation. No changes in uterine structure were found during the first ultrasonographic examination. Three months after abortion and one month after GTN confirmed, massive destruction of lateral uterine wall was detected during transvaginal Doppler ultrasound examination. Resistance index of 0,366 was significantly lower than normal, with hypervascularisation in affected tissue. Serum beta hCG confirmed poor effect of polychemotherapy treatment and decision for operative treatment was made. Hystological findings after the operation confirmed malignant GTN- invasive mole. Specific changes in ultrasonographic picture could have an impact in therapy making decision and could not be refereed without the most relevant parameter such is serum human chorionic gonadotropine.

Fetus sound stimulation: cilia memristor effect of signal transduction.

BACKGROUND: This experimental study evaluates fetal middle cerebral artery (MCA) circulation after the defined prenatal acoustical stimulation (PAS) and the role of cilia in hearing and memory and could explain signal transduction and memory according to cilia optical-acoustical properties. METHODS: PAS was performed twice on 119 no-risk term pregnancies. We analyzed fetal MCA circulation before, after first and second PAS. RESULTS: Analysis of the Pulsatility index basic (PIB) and before PAS and Pulsatility index reactive after the first PAS (PIR 1) shows high statistical difference, representing high influence on the brain circulation. Analysis of PIB and Pulsatility index reactive after the second PAS (PIR 2) shows no statistical difference. Cilia as nanoscale structure possess magnetic flux linkage that depends on the amount of charge that has passed between two-terminal variable resistors of cilia. Microtubule resistance, as a function of the current through and voltage across the structure, leads to appearance of cilia memory with the "memristor" property. CONCLUSION: Acoustical and optical cilia properties play crucial role in hearing and memory processes. We suggest that fetuses are getting used to sound, developing a kind of memory patterns, considering acoustical and electromagnetically waves and involving cilia and microtubules and try to explain signal transduction.

Group A streptococcal cellulitis in the early puerperium.

INTRODUCTION: Infectious diseases caused by Streptococcus pyogenes, a member of the group A Streptococci (GAS) are among the most common life threatening ones. Patients with GAS infections have a poor survival rate. Cellulitis is a severe invasive GAS infection and the most common clinical presentation of the disease associated with more deaths than it can be seen in other GAS infections. According to the literature data, most cases of GAS toxic shock syndrome are developed in the puerperium. However, there are two main problems with GAS infection in early puerperium and this case report is aimed at reminding on them. The first problem is an absence of awareness that it can be postpartal invasive GAS infection before the microbiology laboratory confirms it, and the second one is that we have little knowledge about GAS infection, in general. CASE REPORT: A 32-year-old healthy woman, gravida 1, para 1, was hospitalized three days after vaginal delivery with a 38-hour history of fever, pain in the left leg (under the knee), and head injury after short period of conscious lost. Clinical picture of GAS infection was cellulites. Group A Streptoccocus pyogenes was isolated in vaginal culture. Rapid antibiotic and supportive treatment stopped development of streptococcal toxic shock syndrome (STSS) and potential multiorganic failure. Signs and symptoms of the infection lasted 25 days, and complete recovery of the patient almost 50 days. CONCLUSION: In all women in childbed with a history of fever early after delivery, vaginal and cervical culture specimens should be taken as soon as possible. Early recognition of GAS infection in early puerperium and prompt initiation of antimicrobial drug and supportive therapy can prevent development of STSS and lethal outcome.

An immunological insight into premature ovarian failure (POF).

Premature ovarian failure (POF), a serious life-changing condition that affects young women, remains an enigma and the researchers' challenge. The term POF generally describes a syndrome of gonadal failure before the age of 40, characterized by amenorrhea, sex steroid deficiency and elevated levels of gonadotropins. Infertility and psychological stress are common consequences of this entity the prevalence of which is 0.9-3%. The known cause of this condition includes: genetic aberrations, autoimmune ovarian damage, iatrogenic and environmental factors, although in majority of cases the underlying cause is not identified. For many women in whom the cause of ovarian failure is unknown, autoimmunity may be the pathogenic mechanism. There is currently evidence that some cases of POF are due to faulty recognition of self in the ovary by the immune system, possibly provoked by genetic or environmental factors initiating such immune response. Numerous evidence, including association with multiple autoimmune endocrine disorders, clinical reversibility, transitory estrogen deficiency, histological and immunological features and the demonstration of circulating ovarian antibodies in serum samples from women with POF, have suggested its immunological origin. We discuss the possible role of such an autoimmune process as a cause or consequence of POF including treatment strategies in POF patients.

[Fetal cerebral-umbilical Doppler ratio in prediction of fetal distress in patients with preeclampsia].

BACKGROUND/AIM: The use of color Doppler ultrasonography provides noninvasive observation, confirmation and quantification of pathophysiological processes in fetoplacental circulation in pregnant patients. By blood vessel mapping and the obtained waves spectral analysis it is posible to evaluate vascular resistency of the fetus blood vessels. The aim of the study was to evaluate cerebral-umbilical pulsatility index ratio in fetal circulation in prediction of fetal distress in patients with preeclampsia. METHODS: By measurement of pulsatility indices in medial cerebral and umbilical arteries in 400 patients with uncomplicated pregnancy, normal values were calculated for fetuses from 15-40 weeks. In our study group 70 patients with preeclampsia were included. Cerebral-umbilical (C/U) ratio was calculated after pulsatility indices in medial cerebral artery and umbilical artery determining by the spectral Doppler analysis of flow velocity waveforms in these vessels. Fetal outcome was analyzed by measurement of the Apgar score at the 5th minute and fetal pH at birth. RESULTS: The mean C/U ratio values in the third trimester of normal pregnancy were between 1.8 and 1.9. The mean C/U ratio values in the patients complicated with preeclampsia were significantly lower comparing to normal pregnancies (ANOVA, p < 0.05). The mean 5th minute Apgar score in the study group was 6.35 +/- 1.58, and the mean fetal pH at birth was 7.16 +/- 0.15. Linear regression test showed a highly significant correlation between low C/U ratio and fetal pH at birth in patients with preeclampsia (r = 0.49, p < 0.01). CONCLUSION: The C/U ratio values obtained from spectral Doppler analysis in fetal vessels showed a highly significant correlation with fetal pH at birth in the patients with preeclampsia. The results of our study confirmed the reliability of C/U ratio in estimation of fetal condition in preeclamptic patients. Very low C/U ratio values in patients with preeclampsia indicate that in these fetuses fetal acidosis and fetal distress may be expected.

[Correlation analysis of predictive factors of successful implantation in fertilization in vitro]. / Korelativna analiza predikcionih faktora za uspesnost implantacije u programu vantelesne oplodnje.

INTRODUCTION: Endometrial receptivity as isolated predictive factor of successful implantation, with its specifity is determined with numbered factors. PURPOSE: Purpose of this study was to evaluate significance and correlation between relevant factors using appropriate statistical analyses on term of embryo implantation. MATERIAL AND METHODS: Evaluated group contained 85 women whom according different causes of infertility have been determined for assisted reproduction program. Analysed measurements were: endometrial thickness, assessed hyperechogenity in relation with absolute endometrial thickness (HEA relation) and uterine blood flow (pulsatile index-Pi). Simultaneously were analyzed serum estradiol (E2; pg/ml) and progesterone (P; nmol/l) levels. After these evaluations achieved results were processed with standard statistical pack. Beside that were applied parameter and nonparameter tests with aim to test significancy of difference and multiple regressive analyse (Stepwise). RESULTS: Resulted measured parameters have been presented in basic analyse as middle value (Xrs) from all measurements + SD (standard deviation) and significance of difference is tested by mentioned statistical tests (Table 1). Application of Stepwise analyse, "step by step", has used parameter by parameter based on value which has decreased variability and based on achieved correlative coefficient between dependent uneven and complex of independent uneven values. This procedure confirms best correlation between HEA relation and serum progesterone levels and HEA relation in correlation with associated values: P, E2 and endometrial thickness (Table 1). DISCUSSION: Investigation provided till now shows that embryo quality and endometrial receptivity with highest probability determine success of applied assisted reproduction, successful embryonal implantation There is assessed influence of endometrial receptivity represented trough HEA relation using many folded regressive analyse where qualitative endometrial value has been looked with dependency with other parameters gives picture for high determinancy with hormonal activity and with stimulative ovarian activity. This determinancy could be viewed mostly through serum progesterone levels on day of HCG administration. Correlative relation between qualitative endometrial characteristics on day of HCG administration has high value related to progesterone levels. CONCLUSION: Results presented with this research confirm once again complexity characteristic for factors that play final role in embryo implantation in IVF program. There is presented only one aspect related with this problem with aim to contribute quantification importance and assessment rate of mutual influence these factors known till now as relevant.