Ин витро в Истанбул- тема 19

BRC and CAB have been extensively compared in clinical trials and studies with respect to their side-effect profiles and the relative ease of achieving pregnancy in hyperprolactinemic women [4, 7]. One such study compared BRC and CAB in two groups of patients with hyperprolactinemia and reported that the frequency of galactorrhea and irregular menstruation were found to be lower in women receiving CAB and pregnancy was more frequently achieved among these patients [7].

Once ovulation and fertility is reinstated in women with hyperprolactinemia, there are two main issues during the course of the pregnancy; firstly, the effects of dopamine agonists on early fetal development and the outcome of pregnancy, and secondly, the effect of hormonal milieu on the size of prolactinoma. Of the data available for BRC from 6000 pregnancies studied, it was found that there was no significant difference in the incidence of spontaneous abortions, ectopic pregnancies, trophoblastic diseases or multiple pregnancies and only 1.8% had congenital malformations [4, 8, 9]. CAB studies demonstrated similar results with a frequency of 2.2% congenital malformations [10] which is still lower than the incidence (3.0%) found in the general population [11].

Tumor growth during pregnancy is another concern in this population. Since a rise in estrogen levels induces prolactin synthesis and secretion, it subsequently leads on to lactotroph cell hyperplasia and an increase in tumor size. Moreover, stopping dopamine agonistic therapy during this time period in order to protect the fetus from adverse effects associated with its continuation, causes further growth in the size of prolactinoma. Keeping this in mind, we ordered a repeat MRI for our patient during the second trimester in order to decide whether to withhold CAB therapy during pregnancy. By continuing therapy, we could diminish the size of tumor further such that once she delivered the child, we could hold CAB while she breastfed.

In their study [10], Lebbe et al. evaluated 100 pregnancies for the risk of adverse outcomes in females previously diagnosed with hyperprolactinemia who were being treated with CAB for a month or more before conceiving. Even though all patients had been advised to discontinue CAB as soon as their pregnancies were confirmed, 13 continued with therapy for variable time period. Cumulative fetal dose was calculated as the product of dose of CAB at discontinuation and the length of gestation during which CAB was given. Spontaneous miscarriages occurred in 10% and three medical terminations of pregnancy were performed for fetal malformations (3%). The remaining 84 deliveries resulted in 88 infants, three of whom presenting with a malformation (3.4%). On comparison, a malformation rate of 6.3% was found in the control group. Postnatal development of the children was normal.

A study showed that 78% of the women who received CAB therapy before and/or during early pregnancy delivered, among which 97% were live infants and neonatal abnormalities were recorded in 9% of the cases [12]. The rates of spontaneous abortions, miscarriages, preterm deliveries, embryo-fetal anomalies and postnatal neurological deterioration in children born to hyperprolactinemic mothers receiving CAB have been found as not being significantly different from those in normal pregnancies [12, 13].

M. Laloi-michelin et al. reported four cases of pregnant women who successfully received CAB therapy [6]. Two of these women had gastric intolerance with BRC and tolerated CAB well. A third patient was under treatment with Quinagolide and was switched to CAB due to development of abnormal visual fields. The last case was of a woman who developed persistent headache with BRC treatment and her MRI showed an increase in tumor size. She was switched to CAB in the eighth month of pregnancy following which her tumor regressed. It was suggested that CAB could be used as an alternative treatment only when BRC failed. Similarly, cases have been reported previously where CAB has been employed for treatment of prolactinomas in situations where BRC therapy has failed [14, 15, 16]. It has been deemed to be more effective and better tolerated than BRC and has been associated with the birth of normal full term infants.

We had initially switched our patient from BRC to CAB because of intolerance to the former, following which her Prolactin levels returned to normal limits and she conceived. Weighing the benefits of continuation of therapy during pregnancy against the risk of adverse fetal outcomes, it was decided to prolong CAB treatment throughout gestation at a lower dose. Literature review had shown that the evidence of fetal abnormalities and adverse pregnancy outcomes in such patients was similar to that in the normal population. Moreover, persistent therapy throughout pregnancy meant that the size of the tumor could be condensed to an extent which would later on enable us to withhold therapy after delivery to allow an innocuous period of six months for lactation. In addition, after delivery the effect of pregnancy on growth of macroprolactinoma was no longer a threat, the decision to stop CAB for lactation with a much reduced tumor size was taken. With the exception of cholestatic jaundice which occurred during the 28th week of gestation, the pregnancy was uneventful. Our patient delivered a healthy baby at term.

Conclusion

To conclude, CAB was used safely and effectively to treat macroprolactinoma during pregnancy in our case. However, it is important to discuss with patients about the limited data available on the use of CAB during pregnancy and associated potential adverse effects on the fetus.