multicenter trial that included more than 1500 patients concluded that women with PCOS who were at risk of OHSS and underwent a frozen embryo transfer in a subsequent cycle had a higher live birth rate and lower miscarriage rate than their counterparts who underwent a fresh embryo transfer during the stimulated cycle. Therefore patients should be aware that freezing the embryos up front will not impact negatively on their success rates.

Laparoscopic ovarian drilling, though not commonly practiced anymore, aims at decreasing the mass of androgen-producing thecal cells in the ovary. It can be performed with monopolar cautery or with laser cauterization. Reported ovulation rates range from 50% to 90% with conception rates of 70% cumulatively in young patients. However, studies available to date fail to show a bene t of ovarian drilling over conventional ovarian stimulation or IVF. Although patients are encouraged to conceive on their own after drilling, thus avoiding the risk of OHSS or multiple pregnancy, the risks of having a procedure under general anesthesia, adhesion formation around the ovaries and fallopian tubes, and potentially decreasing ovarian reserve are major drawbacks of this approach.

In conclusion, PCOS is a common endocrinopathy that has the potential to cause substantial metabolic and gynecologic sequelae. Anovulation is the main component of the syndrome responsible for many of its presentations including infertility. Addressing obesity and insulin resistance are extremely important in the management of these patients, and the treatment cascade should always start with diet and weight loss. Clomiphene citrate and letrozole, both oral agents remain as the rst step in treating fertility-associated anovulation. If this fails, a very careful, low-dose gonadotropin stimulation with or without IUI should be next step. IVF will be the last resort for reasons illustrated above. There is insuf-cient data to recommend laparoscopic ovarian drilling over other conventional therapies. Considering that PCOS is a life-long syndrome, a multidisciplinary approach is necessary to take care of these patients at different stages of their lives.

References

1.\ Azziz R. Polycystic ovary syndrome. Obstet Gynecol. 2018;132:321–36.

2.\ American College of Obstetrics & Gynecology. Polycystic ovary syndrome. Practice Bulletin No. 194. Obstet Gynecol. 2018;131:e157–71.

3.\ Zimmerman LD, Setton R, Pereira N, Rosenwaks Z. Contemporary management of polycystic ovarian syndrome. Clin Obstet Gynecol. 2019;62(2):271–81.

4.\ Baskind NE, Balen AH. Hypothalamic-pituitary, ovarian and adrenal contributions to polycystic ovary syndrome. Best Pract Res Clin Obstet Gynecol. 2016;37:80–97.

5.\ Fauser BCJM, Tarlatzis BC, Rebar RW, Legro RS, Balen AH, Lobo R, et al. Consensus on women’s health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Fertil Steril. 2012;97(1):28–38.

6.\ Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al. Harmonizing the metabolic syndrome. A Joint Interim Statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute;

Chapter 11

Hyperprolactinemia

Allison Petrini and Pak H. Chung

Case

A 27-year-old nulligravida with a 1-year history of primary infertility presented with 7 weeks of secondary amenorrhea. She reported menarche at age 12 and previously regular menses with 30-day cycles. Urine pregnancy tests at home were repeatedly negative. Upon questioning, she also revealed that for the past month, she has noticed cloudy white discharge from her breasts bilaterally. The discharge was not bothersome to her; however, in the setting of her amenorrhea, she has become increasingly concerned. She denied any visual disturbance, headaches, heat or cold intolerance, weight change, fatigue, constipation, or diarrhea.

She has been married for 2 years and attempting to conceive for the past year. She was up to date on her annual pap smears and breast examination which have been within normal limits. Her past medical history was signi cant for anxiety and depression. She was just initiated on escitalopram 3 weeks ago but did not take any other medications. She had a surgical history signi cant for a ruptured appendix at age 13 for which she had a laparoscopic appendectomy. Her family history was signi cant for type II NIDDM in her mother and coronary artery disease in her father. She did not have any family history of cancer. She was a nonsmoker, denied illicit drug use, and consumed alcohol minimally. Three months ago, when seen by her gynecologist, she was referred for a work-up of infertility but in the interim developed these symptoms of amenorrhea and galactorrhea.

A. Petrini

Reproductive Medicine and Ob/Gyn, Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Medical College of Cornell University, New York, NY, USA

P. H. Chung (*)

Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Medical College of Cornell University, New York, NY, USA

e-mail: pakchu@med.cornell.edu

P. H. Chung, Z. Rosenwaks (eds.), Problem-Focused Reproductive Endocrinology and Infertility, Contemporary Endocrinology, https://doi.org/10.1007/978-3-031-19443-6_11

(craniopharyngioma, empty sella, Rathke’s cyst, etc.), and systemic diseases (hypothyroidism, chronic renal failure, ectopic production, cirrhosis, seizure disorders, herpes zoster, tuberculosis, etc.). Hypothyroidism can cause hyperprolactinemia, as low free T4 feedback signals the hypothalamus to increase TRH. In addition to enhancing production of TSH, TRH stimulates prolactin release. About 3–10% of women with PCOS have coexistent hyperprolactinemia [4]. Drug-induced hyperprolactinemia involves those that act as dopamine antagonists such as methyldopa, clonidine, metoclopramide, tricyclic antidepressants, and antipsychotics such as risperidone. Lastly, up to 40% of cases are idiopathic.

Prolactinomas account for 30% of functioning pituitary tumors and are one of the most frequent causes of chronic hyperprolactinemia (50%). They are described as either microadenomas (less than 10 mm in size) or macroadenomas (10 mm or larger). About 40% of individuals with hypothyroidism and 30% with renal failure have mild hyperprolactinemia. Acromegaly can be manifested by co-secretion of prolactin with growth hormone.

Diagnostic considerations should rst rule out secondary causes of hyperprolactinemia as listed above. The patient history must initially be assessed. This patient lacked external or historical factors that might cause hyperprolactinemia. Serum prolactin levels vary between 5 and 25 ng/mL in females, although physiological and diurnal variations occur [5]. Initial nonfasting serum prolactin on this patient was elevated, thus a repeat with fasting in the morning was performed and remained high. Her medical history was overall uncomplicated, and while she was started on a selective serotonin reuptake inhibitor, escitalopram was not expected to cause increased prolactin levels. As galactorrhea can be normal in pregnancy, a urine or serum pregnancy test ruled out this cause for her secondary amenorrhea. A normal serum TSH and free T4 excluded hypothyroidism. A normal creatinine level within the basic metabolic panel assures normal renal function. If these tests do not reveal an obvious etiology, regardless of the degree of hyperprolactinemia, imaging of the hypothalamic–pituitary area is indicated. An MRI of the brain with gadolinium enhancement is the appropriate next step. An MRI may be normal but usually reveals a microor macroadenoma of the pituitary. Both forms of pituitary adenomas commonly arise from the lateral wings of the anterior pituitary where lactotrophs are located. However, other possible MRI ndings include empty sella syndrome, other forms of hypothalamic/pituitary tumor, or any pathology that compresses onto the pituitary stalk. In our Center, craniopharyngiomas have been diagnosed in patients with similar presentation as in this patient. Since renal adenomas associated with Cushing’s disease can secrete prolactin, an additional work-up for Cushing’s disease must be considered in those with clinical features compatible with the disease. Compression from a prolactinoma may also diminish the secretion of other anterior pituitary hormones. Therefore, measuring serum gonadotropins, ACTH, growth hormone, or antidiuretic hormone is clinically relevant. In patients with a longer duration of amenorrhea due to hyperprolactinemia, it is prudent to consider DEXA screening for possible decrease in bone mineral density secondary to diminished estrogen.