Gonadotroph Pituitary Adenoma Causing Treatable Infertility and Ovarian Hyperstimulation Syndrome in Female Patients: Neurosurgical, Endocrinologic, Gynecologic, and Reproductive Outcomes.

BACKGROUND: Gonadotroph pituitary adenoma (Gn-PA) may rarely cause ovarian hyperstimulation syndrome, leading to infertility in women, although this remains poorly described. METHODS: We present a quantitative systematic review including 2 patients from our institutional and 48 from the literature with Gn-PA causing ovarian hyperstimulation syndrome to thoroughly describe the clinical features and therapeutic outcomes from multidisciplinary aspects. RESULTS: The patients had a mean age of 31.5 years and a mean follicle-stimulating hormone level of 14.4 IU/L. Estradiol level was high in 82% of patients, at >350 pg/mL. The mean maximal adenoma diameter was 22 mm, with a Knosp grade ≥3 in 10 patients. Abdominal surgery preceded adenoma resection in 24 patients (48%). Among 25 patients for whom extent of resection was recorded, total adenoma resection was achieved in 12. Through a mean follow-up of 25 months, adenoma recurrence was observed in 5 patients, who were treated with re-resection (n = 2), radiation (n = 2), and medical therapy followed by bilateral oophorectomy (n = 1). Medical therapies were partially effective or ineffective, and adenoma shrinkage did not follow; gonadotropin-releasing hormone agonists/antagonists were partially effective in 20% of patients (2/10), dopamine agonists in 44% (8/18), and somatostatin analogues in 50% (1/2). Four experienced swelling of tumor/ovaries after gonadotropin-releasing hormone agonists/antagonists administration. Overall, chemical remission was obtained in 26 of 28 patients, normalization of ovaries in 25 of 27, and successful pregnancy in 12 of 14. CONCLUSIONS: Adenoma resection is the main treatment, leading to reduction in ovarian size and biochemical remission, with a high likelihood of subsequent spontaneous pregnancy. Increased awareness of this rare condition may help avoid unnecessary abdominal procedures.

Functioning gonadotroph adenoma with severe ovarian hyperstimulation syndrome: A new emergency in pituitary adenoma surgery? Surgical considerations and literature review.

The authors reported 2 cases of functioning gonadotroph pituitary adenoma (FGPA) revealed by an ovarian hyperstimulation syndrome (OHSS) in young women. In the first case, OHSS was observed after GnRH analog injection. Pelvic echography revealed multiple voluminous ovarian cysts. Dopamine agonist posology failed in estradiol hypersecretion control, which necessitated endoscopic endonasal transsphenoidal surgery. The patient experienced improvement in pelvic pain as estradiol hypersecretion decreased during the first few postoperative days. Outcome was favorable, and her menstrual cycle was normal after two months. The second case was a young girl with spontaneous pelvic pain and elevated plasma FSH and estradiol levels. FGPA was confirmed on cerebral MRI. Dopamine agonists were introduced, and surgical removal of the pituitary tumor was scheduled for 7 days later. In the meantime, the patient was admitted and underwent surgery for bilateral adnexal torsion related to OHSS. The pituitary tumor was removed one week later. Outcome was favorable, and estradiol and FSH plasma levels were normal after 3 months. The ovarian cysts were no longer visible on echography after 3 months. Given the lack of efficacy of the current standard medical therapy, surgical removal of pituitary adenomas is the reference treatment for FGPA. The authors suggest that severe OHSS related to FGPA should be considered as a relative surgical emergency and that surgery should not be unduly delayed, given the unpredictable risk of adnexal torsion, particularly in case of voluminous ovarian cysts. The authors performed a literature review on this topic.

Cesarean Delivery in a Case of Persistent Second Trimester Ovarian Hyperstimulation Syndrome.

Background Ovarian hyperstimulation syndrome develops as an iatrogenic complication related to ovulation induction. It is usually self-limiting with complete resolution expected within 10-14 days. Case The current case is a report of an unusually prolonged course of ovarian hyperstimulation syndrome persisting until 22 weeks of gestation, accidentally discovered and managed by cesarean section due to an obstetric indication. Conclusion Clinicians should be aware of this possibility when managing cases of IVF pregnancy.

Experience with the bonanno catheter in the management of OHSS from IVF-ET Cycles.

OBJECTIVE: To document our experience with the use of the Bonanno catheter as a closed abdominal drain for OHSS Methods: A retrospective study of all IVF embryo transfer (ET) treatment cycles carried out between May 2006 and April 2009 at a dedicated IVF centre. Case notes of patients with OHSS were retrieved and the outcome of the continuous closed abdominal drain with Bonanno catheter documented. RESULT: Within the period under review, 234 patients had controlled ovarian stimulation with ultrasound guided egg retrieval. Two hundred and twenty eight (228) got to the stage of embryo transfer with 72 clinical pregnancies. The clinical pregnancy rate was 31.58%. Fourteen (6%) of those who were stimulated developed OHSS and had a closed abdominal drain of the ascitic fluid using the Bonanno catheter. The average number of days of the abdominal drainage was 7.5days and the average volume of ascitic fluid drained from a patient per day was 2454.9 + 748mls. Eight (8) patients who had OHSS achieved clinical pregnancy (six intrauterine, one ectopic and one heterotopic pregnancies), giving a clinical pregnancy rate of 57.14% in patients with OHSS. Four patients had blocked Bonanno catheters and three of them had the catheter changed while the fourth had the catheter successfully flushed. Four patients had the insertion site dressing changed due to soaking with ascitic fluid. There was no incidence of injury to intra abdominal organs or broken catheter. CONCLUSION: Bonanno Catheter is both effective and safe in draining ascitic fluid following OHSS.

Association between peak estradiol levels and ovarian torsion among symptomatic patients receiving gonadotropin treatment.

PURPOSE: Ovarian torsion is a surgical emergency that can be clinically challenging to diagnose. Patients who have received assisted reproductive technologies (ART) are a subset of women with an increased risk for torsion. As the ART population continues to increase, there is a need to delineate risk factors for the development of ovarian torsion in this unique population. A pilot study was performed to determine the proportion of patients with suspected ovarian torsion who have received ART and to identify possible diagnostic biomarkers for ovarian torsion among these patients. METHODS: A single institution retrospective cohort study of patients taken to surgery for suspected ovarian torsion over a 5-year period. RESULTS: During the study period, 171 patients were taken to surgery for suspected ovarian torsion. Patients receiving ART constituted 19 (11%) of these patients. Among the 19 fertility treatment patients, 16 had received treatment with gonadotropins, 10 of which had surgically confirmed ovarian torsion. These ten patients had higher preoperative peak estradiol levels (3122 versus 1875 pg/mL, p = 0.05) and a larger ovarian diameter (9.7 versus 7.6 cm, p = 0.05) than the six patients receiving gonadotropins found to not have ovarian torsion. CONCLUSIONS: These results suggest infertility treatment using gonadotropins for ovarian hyperstimulation may be an independent risk factor for ovarian torsion as suggested by the disproportionate number of such individuals represented in the study population (9% of all patients, 84% of fertility patients). Additionally, among women taking gonadotropins, an association exists between peak estradiol levels, ovarian diameter, and risk for ovarian torsion.

Predictors of Paracentesis in Women with Severe Ovarian Hyperstimulation Syndrome: A Retrospective Cohort Study.

BACKGROUND: To identify predictors of paracentesis in women with severe ovarian hyperstimulation syndrome (OHSS). METHODS: In a retrospective cohort study, we assessed patient characteristics and outcome measures of women with severe OHSS Golan grade II/III from 1996 to 2010 using univariate and multivariate analyses with the number of paracenteses as the main outcome. RESULTS: Three hundred ninety four women with OHSS Golan grade II (n = 40) and grade III (n = 354) were included in the study. Paracentesis was performed in 108/394 (27%) of these women. One paracentesis was performed in 63 (16%), 2 paracenteses in 26 (6%), and ≥3 paracenteses 19 (5%) women, respectively. No thrombotic or cerebrovascular morbidity occurred. The mortality of the cohort was 0/394 (0%). In a univariate analysis, late onset OHSS (p = 0.02), pregnancy (p < 0.001), human chorionic gonadotropin use (p = 0.02), ovarian diameter (p = 0.006), and elevated serum levels of alanine aminotransferase (p < 0.001), hematocrit (p < 0.001), leucocytes (p < 0.001), thrombocytes (p < 0.001), and uric acid (p < 0.001) were associated with paracentesis. In a multivariate logistic regression analysis, only alanine aminotransferase (OR 1.006; 95% CI 1.001-1.01) and hematocrit (OR 1.16; 95% CI 1.05-1.27) were independently associated with paracentesis. CONCLUSION: Alanine aminotransferase and hematocrit at initial presentation are independent predictors of paracentesis.

Gonadotroph adenoma causing ovarian hyperstimulation syndrome in a premenopausal woman.

INTRODUCTION: Gonadotroph adenomas occur commonly in middle-aged adults without any specific endocrinological symptoms. To date, only 30 cases of gonadotropinoma causing ovarian hyperstimulation syndrome in pre-menopausal women have been reported. CASE REPORT: A 37-year old woman with pituitary macroadenoma and hyperprolactinaemia was admitted to the Department of Endocrinology, Diabetology and Isotope Therapy. She presented with recurrent ovarian cysts, menstrual disturbances, headaches, visual impairment and galactorrhea. Her endocrine profile showed normal values of FSH, elevated concentrations of estradiol and suppressed LH levels. Transsphenoidal resection of the tumor tissue resulted in normalization of the hormone values and improvement in the clinical picture. CONCLUSIONS: Gonadotroph adenomas should be considered in the differential diagnosis in premenopausal women with OHSS.

Assessment of cells in the ascitic fluid of women with ovarian hyperstimulation syndrome: the clinical implications for subsequent ovarian malignancy.

BACKGROUND: Although some studies have reported a potential connection between ovulation induction therapy (OIT) and malignant ovarian diseases, the results have been inconclusive. In the present study, we sought to determine whether women undergoing OIT at our in vitro fertilization (IVF) clinic, especially those with severe ovarian hyperstimulation syndrome (OHSS) and suspicious cytologic findings, were at risk for developing malignant ovarian tumours after treatment. METHODS: Patients who underwent OIT at our IVF clinic were enrolled in this study and assessed for any evidence of malignant ovarian tumours. Patients who developed severe OHSS as a result of OIT were treated with a culdocentesis. Cells from the ascitic fluid were cytologically scored for abnormality and malignancy. Peripheral blood samples were obtained from patients with severe OHSS to determine serum levels of the tumour markers (CA-125 and HE4) that were used to calculate the Risk for Ovarian Malignancy Algorithm (ROMA) index. RESULTS: Follow-up data were available for 1,353 of the 1,587 patients (85%) who underwent OIT at our IVF clinic between January 2006 and December 2012. Twenty-three patients (1.4%) were hospitalized with OHSS. Culdocentesis was performed 16 times in nine patients with severe OHSS (age range, 23-34 years; mean, 27.1 years). Although cytological examination of the ascitic cells of these patients suggested malignant ovarian neoplasia, over the course of the observation period, the ovarian volume gradually decreased and became normal. Subsequent cytological and histological examinations failed to find evidence of any malignant tumours in these nine patients. None of the 1,353 participants who underwent OIT developed any malignant ovarian tumours during the study period. Moreover, none of the 462 patients who were in our ovarian tumour registry were also participants in the IVF program. CONCLUSIONS: The presence of atypical cells in the ascitic fluid of women with severe OHSS does not likely indicate malignancy; therefore, radical surgical intervention is not justified. The risk of malignancy is minimal shortly after OIT. At our centre, OIT has not been associated with any cases of ovarian tumour.

[Ovarian torsion after controlled ovarian hyperstimulation: 5 cases report and clinical analysis].

OBJECTIVE: To evaluate the characteristics and treatment of ovary torsion after controlled ovarian hyperstimulation. METHODS: Between Jan.2008 and Dec.2011, 5 cases with ovary torsion who underwent ovarian hyperstimulation were retrospectively studied. RESULTS: Five cases presented intermittent lower abdominal from 1 to 38 days after oocyte retrieval. Enlargement of ovary and decreased or absent venous and/or arterial flow were demonstrated by Doppler sonography. Two torsions at left side, two torsions at right side, and one on bilateral side were observed. Three cases give up embryo transplantation, 2 cases were pregnant after surgical treatment. One case with partial torsion was successfully treated with simple conservative treatment. Two cases with complete torsion were performed adnexectomy by laparotomy. One case with complete torsion with early pregnancy was managed by laparoscopic adnexectomy. One case with chemical pregnancy was managed by laparoscopic detorsion for left side and excision for right side. Postoperative pathology of ovary tissue all confirmed haemorrhage and necrosis. CONCLUSIONS: Ovary torsion might occur after controlled ovarian hyperstimulation. The early management on ovary torsion will be benefit for preserving ovarian function.

Ovarian salvage in bilaterally complicated severe ovarian hyperstimulation syndrome.

OBJECTIVE: To report the management of 2 cases of severe ovarian hyperstimulation syndrome (OHSS) bilaterally complicated by rupture and late subsequent torsion. DESIGN: Two case reports. SETTING: Obstetrics and Gynecology department of a hospital. PATIENT(S): Case 1: Severe OHSS complicated by massive intraperitoneal hemorrhage and bilateral extensive ovarian rents and rupture at multiple sites. Case 2: Twin IVF pregnancy and late severe OHSS complicated further by subsequent bilateral torsion. INTERVENTION(S): Case 1: Diagnosed by clinical, hematologic, and ultrasound findings. Resuscitation, laparotomy, and meticulous ovarian repair with suture, glue, and hemostat affected bilateral ovarian conservation. Case 2: Diagnosed clinically and confirmed by color Doppler. Left salpingoopherectomy was performed because of a devitalized left ovary; 3 days later laparoscopic right ovarian detorsion and aspiration was possible as early Doppler diagnosis was made. MAIN OUTCOME MEASURE(S): Case 1: ovarian conservation. Case 2: ovarian conservation and continuation of pregnancy. RESULT(S): Case 1: Recovery and normal serum FSH and E(2) 2 months postsurgery. Case 2: Continuation of pregnancy and the remaining ovary was healthy at abdominal delivery. CONCLUSION(S): Two cases of bilaterally complicated severe OHSS in which the patients' safety and bilateral ovarian integrity were at jeopardy. The cases are presented to define the importance of awareness, early diagnosis, and intervention, as well as the use of various methods and techniques to affect preservation of ovarian integrity and reserve.

Ovarian hyperstimulation syndrome in a patient treated with tamoxifen for breast cancer.

OBJECTIVE: To report the management of a rare case of ovarian hyperstimulation syndrome (OHSS) induced by tamoxifen therapy for breast cancer in a 50-year-old woman. DESIGN: Case report. SETTING: Gynecology outpatient department of a university hospital. PATIENT(S): A 50-year-old premenopausal patient with a history of breast cancer was prescribed adjuvant treatment with tamoxifen. INTERVENTION(S): Temporary discontinuation of tamoxifen therapy resolved symptoms, but resumption of tamoxifen caused a recurrence of symptoms. Surgical bilateral salpingo-oophrectomy was therefore performed. MAIN OUTCOME MEASURE(S): Resolution of symptoms of OHSS. RESULT(S): Bilateral salpingo-oophrectomy rendered the patient postmenopausal and enabled the commencement of the aromatase inhibitor anastrozole as an alternative adjuvant therapy for breast cancer. CONCLUSION(S): Tamoxifen-induced OHSS is rare. Furthermore, OHSS is very rare in the older female. OHSS usually resolves with temporary discontinuation of tamoxifen, however, the recurrence of symptoms when resuming tamoxifen is better treated with bilateral salpingo-oophorectomy to enable adjuvant treatment with anastrazole.

Sextuplet heterotopic pregnancy presenting as ovarian hyperstimulation syndrome and hemoperitoneum.

OBJECTIVE: To describe a case of bilateral ruptured heterotopic pregnancies presenting as persistent ovarian hyperstimulation syndrome in a quadruplet pregnancy. DESIGN: Case report. SETTING: University hospital and clinic. PATIENT(S): An infertile patient who conceived using gonadotropin therapy. INTERVENTION(S): Culdocentesis with resultant aspiration of sanguinous fluid prompted laparoscopic exploration and bilateral salpingectomies. MAIN OUTCOME MEASURE(S): Not applicable. RESULT(S): Gross hemoperitoneum and ruptured bilateral heterotopic sextuplet pregnancy. CONCLUSION(S): Patients who conceive after gonadotropin therapy should be closely monitored during treatment and in early pregnancy to recognize and minimize morbidity and complications. After superovulation, the presence of an intrauterine pregnancy, either single or multiple, does not rule out the possibility of ectopic pregnancy, and this should always be considered as a possibility in the setting of acute anemia.

Desarrollo de síndrome de hiperestimulación ovárica grave tras la administración exógena de gonadotropina coriónica humana / Severe ovarian hyperstimulation syndrome after exogenous administration of human chorionic gonadotropin

El síndrome de hiperestimulación ovárica grave esuna entidad clínica que puede ocurrir tras la administraciónde gonadotropina coriónica humana, utilizadapara inducir la ovulación en las pautas de estimulaciónovárica de la fecundación in vitro. Presentamos el casode una mujer de 27 años, que tras recibir tratamientocon gonadotropina y ser sometida a fertilización in vitroconsiguiendo gestación, presentó un cuadro clínico dedolor abdominal, ascitis, edemas en miembros inferiores,disnea, derrame pleural bilateral y síndrome de distrésrespiratorio del adulto. La paciente precisó ingreso en launidad de cuidados intensivos y ventilación mecánica,así como la realización de legrado uterino para frenar laprogresión del cuadro(AU)

Severe ovarian hyperstimulation syndrome can occurafter administration of human chorionic gonadotropinused to induce ovulation in the context of in-vitrofertilization protocols. We report the case of a 27-yearoldwoman who had received gonadotropin treatment.In-vitro fertilization was successful but she developedabdominal pain, ascites, lower limb edema, dyspnea,bilateral pleural effusion, and adult respiratory distresssyndrome. The patient was admitted to the intensive careunit, where mechanical ventilation was started. Uterinedilatation and curettage was required to halt the process(AU)

Ovarian hyperstimulation syndrome in a spontaneous pregnancy with a complete hydatidiform mole.

OBJECTIVE: To present a case of ovarian hyperstimulation syndrome occurring after evacuation of a spontaneously conceived hydatidiform molar pregnancy. DESIGN: Case report. SETTING: University-affiliated teaching hospital. PATIENT(S): A 19-year-old nulliparous woman who underwent vacuum curettage for a complete hydatidiform molar pregnancy was admitted to our hospital with ovarian hyperstimulation syndrome and large bilateral pleural effusions. INTERVENTION(S): Intravenous fluid, deep vein thrombosis prophylaxis, placement of bilateral chest tubes. MAIN OUTCOME MEASURE(S): Management of ovarian hyperstimulation syndrome. RESULT(S): Ultrasonography and computed tomography showed large multicystic ovaries, marked ascites, and large pleural effusions that required placement of bilateral chest tubes. She had recovered by hospital day 14. CONCLUSION(S): Ovarian hyperstimulation syndrome may develop in women who have undergone treatment for a hydatidiform mole, and serious complications may develop rapidly.

[Anesthetic management of a patient with severe ovarian hyperstimulation syndrome].

We report anesthetic management of a patient with severe ovarian hyperstimulation syndrome (OHSS). A 33-year-old woman presented with severe abdominal acites and effusion after ovarian stimulation with HMG followed by ovulation induction with HCG. She was suspected of having intraabdominal hemorrhage because of ectopic pregnancy. Emergency laparotomy was performed under general anesthesia. Massive ascites and intraabdominal hemorrhage were observed and patient was treated by adequate fluid infusion and blood transfusion. Patient was treated with non-invasive positive pressure ventilation (NPPV) after operation and recovered. It is essential to maintain a correct balance of fluids, through appropriate intravenous infusion of crystalloids, albumin, blood transfusion and an adequate urine output. Further it is important to prevent thromboembolic event. Knowledge of the clinical features, complications and acute management of OHSS will permit the anesthesiologist to treat these patients in an optimal fashion.

[Clomiphene, ovarian hyperstimulation syndrome and pregnancy].

In case of an ovarian hyperstimulation syndrome surgical treatment causes the regress of symptoms much faster than pharmacotherapy--during the resection of an ovary the concentration of estrogenes in blood is effectively reduced. Frequent use of ovulation inductors (Clomiphene Gonadotrop(h)in) is accompanied by ovarian hyperstimulation syndrome. It is characterized by the increase of sizes of ovaries; the formation of ascites and hydrothorax, by the thromboemboly of main blood vessels and etc. Clomiphene accelerates the maturation process of follicles, but contributes to the increase of concentration of oncomarker CA-125 in blood. This makes it difficult to verify the diagnosis of ovary cancer, particularly among pregnants. The case report of infertility treatment with Clomiphene is depicted. Woman became pregnant after three courses of infertility treatment, but pregnancy was complicated with cardiac and lung insufficiency; the suspicion of stage III ovarian cancer aroused. Serious threat to health of a woman resulted in prevention of pregnancy. Right side adnexectomy was conducted. Surgical treatment led to improvement and after four years the patient delivered a healthy child.

[Severe ovarian hyperstimulation syndrome after exogenous administration of human chorionic gonadotropin]. / Desarrollo de síndrome de hiperestimulación ovárica grave tras la administración exógena de gonadotropina coriónica humana.

Severe ovarian hyperstimulation syndrome can occur after administration of human chorionic gonadotropin used to induce ovulation in the context of in-vitro fertilization protocols. We report the case of a 27-year-old woman who had received gonadotropin treatment. In-vitro fertilization was successful but she developed abdominal pain, ascites, lower limb edema, dyspnea, bilateral pleural effusion, and adult respiratory distress syndrome. The patient was admitted to the intensive care unit, where mechanical ventilation was started. Uterine dilatation and curettage was required to halt the process.