Importance of macroprolactinemia in hyperprolactinemia.

Macroprolactin is an antigen-antibody complex of higher molecular mass than prolactin (>150kDa), consisting of monomeric prolactin and immunoglobulin G. The term 'macroprolactinemia' is used when the concentration of macroprolactin exceeds 60% of the total serum prolactin concentration determined by polyethylene glycol precipitation. The gold standard technique for the diagnosis of macroprolactinemia is gel filtration chromatography. The prevalence of macroprolactinemia in hyperprolactinemic populations varies between 15% and 35%. Although the pathogenesis of these antibodies is not clear, it is possible that changes in the pituitary prolactin molecule represent increased antigenicity to the immune system, leading to the production of anti-prolactin antibodies. Mild hyperprolactinemia usually occurs because macroprolactin is not cleared readily from the circulation due to its higher molecular weight. Moreover, the hypothalamic negative feedback mechanism for autoantibody-bound prolactin is inactive because macroprolactin cannot access the hypothalamus, resulting in hyperprolactinemia. Reduced in-vivo bioactivity of macroprolactin may be the reason for the lack of hyperprolactinemic symptoms. It also seems that anti-prolactin autoantibodies may compete with prolactin molecules for receptor binding, resulting in low bioactivity. Additionally, the large molecular size of macroprolactin confined in the intravascular compartment prevents its passage through the capillary endothelium to the target cells, which may be the reason for the lack of symptoms. Macroprolactinemia is considered to be a benign clinical condition in patients with normal concentrations of bioactive monomeric prolactin, with a lack, or low incidence, of hyperprolactinemic symptoms and negative pituitary imaging. In such cases with resistance to anti-prolactinaemic drugs, no pharmacological treatment, diagnostic investigations or prolonged follow-up are required. However, macroprolactinemia may also occur in patients with conventional symptoms of hyperprolactinemia who cannot be differentiated from patients with true hyperprolactinemia. These symptoms are mainly attributed to excess levels of monomeric prolactin, and this is of concern. The diagnosis of macroprolactinemia is misleading and inappropriate. A multitude of physiological, pharmacological and pathological causes, including stress, prolactinomas, hypothyroidism, renal and hepatic failure, intercostal nerve stimulation and polycystic ovary disease, can contribute to increased levels of monomeric prolactin. It is important for patients with elevated monomeric prolactin levels to undergo routine evaluation to identify the exact pathological state and introduce adequate treatment, regardless of the presence of macroprolactin. In addition, macroprolactinemia occasionally occurs due to macroprolactin associated with pituitary adenomas, with biological activity of macroprolactin comparable with that of monomeric prolactin. In cases when excess macroprolactin occurs with clinical manifestations of hyperprolactinemia, macroprolactinemia should be regarded as a pathological biochemical variant of hyperprolactinemia. An individualized approach to the management of such patients with macroprolactinemia may be necessary, and pituitary imaging, dopamine treatment and prolonged follow-up should be applied.

Breast cancer treatment--later pregnancy and survival.

Although breast cancer (BC) affects patients at older age, it occurs more frequently in premenopausal women due to better diagnostic methods and an increasing trend towards delay in childbearing. The increasing population of women with BC delaying childbearing may be of concern regarding the effect of treatment on later pregnancy, as well as the influence of pregnancy on the prognosis of disease and survival. Radiotherapy has shown no adverse effects on the clinical outcome in the offspring except diminished lactation. The offspring of patients who became pregnant after chemotherapy have shown no congenital anomalies, although sometimes a high abortion rate (10-29%) has been demonstrated. Currently, several fertility-sparing options, including the use of endocrine therapy and assisted reproductive technologies, cryopreservation and ovarian tissue transplantation, are very promising. The survival of BC patients is not decreased by a subsequent pregnancy; compared with the non-pregnant group their survival rates are often the same or better, with favourable relative risks and lower recurrence of metastases.

Combined interstitial and intrauterine pregnancies after in-vitro fertilization and embryo transfer.

A case of combined interstitial and intrauterine pregnancies after bilateral salpingectomy and in-vitro fertilization with embryo transfer is reported. The case was incorrectly diagnosed ultrasonographically as intrauterine triplets at 7 weeks gestation. The patient suffered from intra-abdominal bleeding at 14 weeks gestation. At laparotomy, a ruptured left interstitial pregnancy with a non-viable fetus was found in the left abdominal quadrant. The uterine defect was successfully repaired and gestational contents and blood were evacuated from the abdominal cavity. The intrauterine twin pregnancy progressed without incident, and a Caesarean section was performed at 36 weeks gestation, resulting in healthy male and female infants.

Simultaneous bilateral tubal pregnancy following in-vitro fertilization and embryo transfer.

A case of simultaneous bilateral tubal pregnancy resulting from in-vitro fertilization and embryo transfer is presented. Repeated transvaginal ultrasound examinations confirmed an intrauterine sac but no fetus. A diagnosis of early missed abortion was incorrectly made and a curettage was performed. The pathological examination showed the presence of decidua and Arias-Stella phenomenon but no chorionic villi. Diagnostic laparoscopy and laparotomy performed 40 days after embryo transfer (eighth week of gestation), revealed bilateral tubal pregnancy. Bilateral salpingectomy was performed.

[Pregnancy outcome after conization]. / Ishod trudnoce nakon konizacije.

The outcome of pregnancy in 68 women with previously made conisation of the uterine cervix is presented. As a control group were 68 pregnancies which were the first in the protocol following the examined ones. Of 68 women of observed group there were 45 (66.2%) term deliveries, 10 (14.7%) preterm deliveries, and 13 (19.1%) spontaneous abortions, while in women of control group the results were 52 (76.5%), 6 (8.8%) and 10 (14.7%) respectively. This did not represent a statistical significance (chi 2 = 1.89; p less than 0.05). In the first desired pregnancy after conisation 43 (63.2%) women were resting in bed and taking medicaments, 20 (29.4%) had cervical cerclage, while in women of the control group there were 14 (20.6%) and 5 (7.4%), respective what represents statistically significant difference (chi 2 = 25.4; p less than 0.01; chi 2 = 11.3; df = 1, p less than 0.01). Of 43 women of observed group with resting and medicaments in pregnancy 33 (76.7%) had term deliveries, 8 (18.6%) preterm deliveries and 2 (4.7%) spontaneous abortions, while in 25 women without resting and no medicaments, the results were 13 (52%), 11 (44%), 1 (4%) respectively. This represents statistical significant difference (chi 2 = 4.42; p less than 0.05). In the control group of 54 women without resting and no medicaments, there were 45 (83.3%) term deliveries, 3 (5.6%) preterm deliveries and 6 (11.1%) spontaneous abortions, while in 25 women after conisation and no resting there were 13 (52%), 11 (44%), 1 (4%) respectively. This represents a statistical significance (chi 2 = 8.59; p less than 0.01). (ABSTRACT TRUNCATED AT 250 WORDS)