The relationship between SPAs and pregnancy has not been sufficiently investigated. Our study of 30 patients with silent pituitary adenoma revealed 92 pregnancies overall. There were 66 live births (71.7%), 12 elective abortions (13%), seven missed abortions (7.5%), and four stillbirths (4.3%). To assess the potential complications and mortality rates associated with childbirth, it is essential to consider the national data specific to the country, and we analyzed our data in this manner. According to the Turkey Demographic and Health Survey 2018 (TNSA-2018), from 2013 to 2018, 6% of pregnancies resulted in elective abortion, 13% in a missed abortion, 1% in a stillbirth, and 80% in a live birth 9. Our findings suggest that silent pituitary adenomas do not significantly affect the rates of elective and missed abortions, as they were similar to the national averages. The incidence of stillbirths in the study population (4.3%) was higher than the national average (1%); the pathophysiology behind this is unknown. Confirmation of these data is needed, and if verified, additional research is required to investigate the underlying mechanisms. Twelve percent of all live births were of low birth weight in our study, which was the same as the national rate. Additionally, the average lactation duration was 16 months, which is similar to the median duration of breastfeeding of 16.7 months reported in the national data. However, the small sample size and lack of sociodemographic data suggest caution in interpreting these relationships. Nonetheless, the results of the study are presumed to be comparable to those in the country. This study highlights the importance of further investigating the potential impact of pituitary adenomas on pregnancy outcomes.
The literature suggests that an NFPA can impact fertility and result in rare pregnancies due to the effects of gonadotropin production and hyperprolactinemia 10. However, only two of our 30 patients had a history of in vitro fertilization, and one had a history of insemination. Patients with hypogonadotropic or hypergonadotropic hypogonadism were excluded, and those with a normal hormone panel were included. Our findings suggest that fertility was not affected in this population.
An increase in the size of NFPAs has been reported on rare occasions due to tumor growth, infarction, or hemorrhage during pregnancy 11. Karaca et al. performed MRI of the pituitary in one patient, and the adenoma did not enlarge. No compression symptoms were observed during pregnancy 7. Similarly, MRI scans confirmed that there was no adenoma growth in our study.
We evaluated pregnancy-related complications and found that the incidence of gestational diabetes mellitus (GDM) was 6.1% of all live births, pregnancy-related hypertension was 6.1%, and preeclampsia was 1.5%. According to the literature, GDM occurs at a rate of 0.06–15% 12, pregnancy-related hypertension occurs at a rate of 6–10% 13, and preeclampsia occurs at a rate of 3–5% 14. In a United Kingdom study of 16 pregnant patients with nonfunctional pituitary adenoma, one patient (6.25%) had pregnancy-related hypertension without preeclampsia 6. However, our findings suggest that a silent pituitary adenoma is not associated with an increased risk of GDM, pregnancy-related hypertension, or preeclampsia.
Regarding the chosen delivery method, 26 (39.4%) patients were delivered via cesarean section. Our national rate of elective cesarean sections is 47.5% 15. UK researchers found that 50% of individuals with NFPAs underwent cesarean delivery, compared to 24% of the general population 6. However, our study did not find any evidence of an increased risk of cesarean section in these patients, despite high rates nationally.
Comparing pregnancy characteristics between patients with macroadenoma and microadenoma, our data show no statistically significant differences between the two groups regarding the frequency of missed abortions, ectopic pregnancies, and stillbirths. Regarding symptoms, there was no statistically significant difference between groups in polyuria, polydipsia, and headache. However, headaches were seen in 17.3% of the microadenoma group and 28.6% of the macroadenoma group. Although this difference is not statistically significant, the higher incidence in the macroadenoma group may be associated with adenoma enlargement caused by lactotroph cell hyperplasia during pregnancy and an increase in dural pressure caused by the macroadenoma, as reported in the literature 16. The significantly higher incidence of visual disturbances in the macroadenoma group may be due to optic chiasm compression. However, we did not observe apoplexy, altered consciousness, or ophthalmoplegia, which are rare complications reported in the literature. There were no statistically significant differences among live births in gestational age, birth weight, and duration of lactation between the groups. Our findings showed no correlation between the size of a pituitary adenoma and unfavorable pregnancy outcomes.
Our study found that 13 of 92 pregnancies occurred in patients who had silent pituitary adenoma before pregnancy. One of the pregnancies resulted in a missed abortion in the 6th week. No ectopic pregnancy or stillbirth was observed, and the remaining 12 pregnancies resulted in live births. The patient with the missed abortion had a microadenoma. Of the pregnancies that resulted in live births, three had macroadenomas, and nine had microadenomas. No symptomatic growth or mass effect was observed in any patients during pregnancy in our study. Although a size increase in SPAs is rare during pregnancy, visual loss and apoplexy have been reported in the literature 17,18. However, according to the literature and our study, the risk of symptomatic growth appears to be very low, especially in microadenomas.
The average time to conceive after contraception was 3.5 months (median 2.5 months) (1–12). No patients used assisted reproductive techniques. In a study by Karaca et al., spontaneous pregnancy occurred in seven patients (87.5%) (1 patient using cabergoline and six patients receiving no treatment). In contrast, one secondary hypogonadism patient became pregnant with ovulation induction. Our study’s high spontaneous pregnancy rates may be related to the absence of hypogonadism and medical treatment history in our patients. The average birth weight in our study was 3154 grams (median 3225 grams, 2300–3840); it was 2500 g or less in two cases (16.6%). There were no cases of macrosomia. In Karaca et al., one of six live births (16.6%) was macrosomic, but no additional problems were detected 7. No adverse effects of silent pituitary adenoma on fetal development have been demonstrated.
A recently published case series includes three additional examples of NFPA associated with pregnancy. Two were histologically verified as gonadotrophic adenomas, and one patient experienced complications during pregnancy. In the first case, a 38-year-old woman was referred during the 32nd week of spontaneous pregnancy after a pituitary macroadenoma was diagnosed based on gradual sight loss. Her prolactin levels were elevated. She experienced diplopia and headaches despite taking dopamine agonists and corticosteroids. She was induced in the 34th week and gave birth to a healthy infant. Transsphenoidal surgery was performed, and pathology indicated a gonadotrophic adenoma. She regained her vision and maintained normal pituitary function. In the second case. Transsphenoidal surgery confirmed a gonadotrophic adenoma (macroadenoma). Two years after surgery, she gave birth to a healthy infant. In the last case, two years after the incidental diagnosis of a pituitary microadenoma, the patient became pregnant without any difficulties 8.
The limitations of our study include the small sample size and difficulty in accessing all the data due to the retrospective design. Furthermore, we excluded patients with hormonal abnormalities and a history of medical treatment to minimize confounding factors. This resulted in a selected population for evaluating the effects of SPAs on pregnancy. Of the 66 pregnancies resulting in live births in our study, 13 were diagnosed before pregnancy, while the remaining 53 pregnancies occurred before diagnosis. However, since all of these patients were asymptomatic, there may have been a delay in the diagnosis, and adenomas may have been present during the pregnancies.
In conclusion, although there may be more symptoms during pregnancy suggesting adenoma growth in patients with macroadenomas, compared to those with microadenomas, these symptoms do not directly reflect tumor size increase. According to our findings, SPAs did not have any adverse effects on pregnancy outcomes, fetal development, or lactation.