Sellar collision tumor involving pituitary gonadotroph adenoma and chondroma: a potential clinical diagnosis

We report on a 74-year-old male patient who presented with progressive neuroophthalmologic symptoms soon after the administration of a long-acting gonadotropin-releasing hormone agonist for treatment of a prostate cancer. Imaging revealed a destructively growing and extensively calcified sellar mass inconsistent with a pituitary adenoma. A transseptal transsphenoidal tumor mass reduction yielded a histological diagnosis of a collision tumor comprised of a gonadotroph adenoma intermingled with osteochondroma. We discuss a potential causal relationship between the administration of the long-acting gonadotropin-releasing hormone agonist and the sudden appearance of the previously unsuspected sellar lesion. Although the association of these two tumors is very likely coincidental, the possibility of causal relationship is addresse

Luteal-phase support in assisted reproductive technology: An ongoing challenge

It has been shown that in controlled ovarian hyper stimulation cycles, defective luteal phase is common. There are many protocols for improving pregnancy outcomes in women undergoing fresh and frozen in vitro fertilization cycles. These approaches include progesterone supplements, human chorionic gonadotropin, estradiol, gonadotropin-releasing hormone agonist, and recombinant luteinizing hormone. The main challenge is luteal-phase support (LPS) in cycles with gonadotropin-releasing hormone agonist triggering. There is still controversy about the optimal component and time for starting LPS in assisted reproductive technology cycles. This review aims to summarize the various protocols suggested for LPS in in vitro fertilization cycles. Key words: Luteal-phase support, IVF, HCG, Progesterone, GnRH agonist, Recombinant LH

Aвтоимун тироидит по долга употреба на агонист на гонадотропин- ослободувачки хормон како третман за предвремен централен пубертет – приказ на случај

There is a small number of studies that have reported abnormalities in endocrine function after a long-term gonadotropin-releasing hormone agonist (GnRHa) treatment in girls. This treatment is considered as safe and effective by most authors. We report our second case of unusual outcome of long-term GnRHa therapy in a girl with central precocious puberty (CPP) of idiopathic or familial etiology. She has received monthly depot of injections of triptorelin for a time period of 4 years. We have examined thyroid function by measuring serum levels of thyrotropin (TSH), thyroxine (T4), thyroid antibodies and ultrasound of thyroid gland. At the age of 11 years she developed a mild goiter and presented with autoimmune thyroiditis, having elevated thyroid antibodies and ultrasound of thyroid gland typical for Hashimoto thyroiditis. Having in mind these two cases, we suggest a closer monitoring of thyroid function in girls with CPP, before and during therapy with GnRH agonist.Постојат мал број студии кои пријавиле нарушувања на ендокрината функција по долга употреба на агонист на гонадотропин – ослободувачки хормон (ГнРХа) кај девојчиња. Овој третман е опишан како безбеден и ефикасен од повеќе автори. Прикажуваме случај на невообичаен исход по долготрајна терапија со ГнРХа кај девојче со централен предвремен пубертет (ЦПП) од идиопатска или фамилијарна етиологија. Во период од 4 години, девојчето примало еднаш месечно трипторелин депо. Ние ја испитавме функцијата на тироидната жлезда со мерење на серумските нивоа на тиротропин (ТСХ), тироксин (Т4), тироидни антитела и ултразвук на тироидната жлезда. На 11 години таа развила блага гушавост презентирана како автоимун тироидит, со покачени тироидни антитела и тироидна жлезда типична за Хашимото тироидит. Затоа, предлагаме редовно следење на функцијата на тироидната жлезда кај девојчиња со ЦПП пред и за време на терапија со агонист на ГнРХ

Correction to “Does the repeat dose of gonadotropin-releasing hormone agonist trigger in polycystic ovarian syndrome improve in vitro fertilization cycles outcome? A clinical trial study” [Int J Reprod BioMed 2020; 18: 485-490]

This is a corrigendum to “Does the repeat dose of gonadotropin-releasing hormone agonist trigger in polycystic ovarian syndrome improve in vitro fertilization cycles outcome? A clinical trial study” [Int J Reprod BioMed 2020; 18: 485-490] and does not have an abstract. Please download the PDF or view the article HTML

Prediction of efficacy of gonadotropin releasing hormone agonist trigger for final oocyte maturation through post-trigger 12-hour luteinizing hormone, follicle stimulating hormone and progesterone levels in COS: a prospective study

Background: Circulating levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and progesterone (P4) in serum after administration of gonadotropin releasing hormone agonist (GnRHa) trigger for final oocyte maturation are found to be predictive of oocyte maturity. This prospective study was conducted at a tertiary care centre to evaluate relationship between serum LH, FSH and P4 levels at 12-h post-trigger and oocyte maturity rate and to predict which hormone has maximum sensitivity and specificity for appropriate oocyte maturation.Methods: Women at risk of ovarian hyper-stimulation syndrome who underwent either autologous or donor IVF cycle treated with flexible GnRH antagonist protocol were taken as participants of the study. GnRHa as trigger for final oocyte maturation was given. After 12 hours of agonist trigger, blood sample was drawn to assess LH, FSH and P4 levels in serum. Continuous variables were expressed as mean±SD. Independent sample t test was used for continuous variables which were normally distributed and Mann-Whitney U test for data not normally distributed. Main outcome measures were number of oocytes retrieved, oocyte maturity rate, fertilization rate, cleavage rate and grade of embryos.Results: There was a statistically significant reduction in number of retrieved oocytes, maturity rate, fertilization rate and grade 1 embryos with a concentration of serum LH and P4 less than the cut off value (p < 0.05).Conclusions: Serum LH and P4 level less than the cut off value at 12-hour post-trigger with GnRHa is associated with a dramatically less oocyte maturity rate and fertilization rate

The Effects of Puberty Blocking Treatment (Gonadotropin Releasing Hormone Agonist) On Physical Activity and Reproductive Health in Young Female Rats

The number of adolescents identifying as transgender has been increasing with many transgender youth receiving treatment with a gonadotropin releasing hormone agonist (GnRHa) that suppresses sex hormone production (i.e., puberty blocker). Transgender individuals taking a GnRHa to block puberty have reported improved mental wellbeing, but the physiological impacts need to be examined. Purpose: To investigate the effects of puberty blocking treatment using GnRHa on physical activity, reproductive morphology, and reproductive function in young female rats. Methods: Four-week old female Sprague Dawley rats were given daily subcutaneous injections of the GnRHa triptorelin or saline as control. One group of rats was housed in cages outfitted with a voluntary running wheel to monitor physical activity while treatment continued for 4-weeks. At eight weeks old, non-wheel running rats were euthanized and the uterus and ovaries were removed for H&E staining or flash frozen to assess morphology and DNA methylation. An additional group was taken off GnRHa treatment for 4-weeks to examine recovery of reproductive organ morphology and DNA methylation. The final group was taken off GnRHa treatment and housed with fertile males to determine reproductive performance. Results: Animals treated with the GnRHa had a significant reduction in total wheel running distance. Daily wheel running analysis showed a significant main drug effect, main time effect, and time x drug interaction. The reduction of wheel running activity began on day-5 and continued until the final day-28. The puberty blocked rats also had a significantly greater body mass than controls. GnRHa treatment led to a reduction in the mass of uteri and ovaries which recovered after 4-weeks of drug withdrawal. The myometrial and endometrial thickness of the uterus was reduced in GnRHa treated animals. The ovaries of puberty blocked animals exhibited a disruption in follicle development and corpora lutea health. The morphology of the uterus and ovaries recuperated after 4-weeks of drug withdrawal. With respect to reproductive performance, no significant difference in pregnancy rate was detected; however, both the number of days until pregnancy detection and number of days until giving birth were considerably longer in GnRHa rats following withdrawal. The number of pups per litter was also significantly reduced by puberty blocking treatment but no abnormalities were observed in the pups. Conclusion: Young female rats treated with a GnRHa had significantly reduced voluntary wheel running, increased body mass, and developmental delay of the reproductive organs. After 4 weeks of GnRHa withdrawal reproductive organ mass and morphology recovered. A minor disruption in reproductive function was detected immediately following GnRHa withdrawal. These physiological effects on physical activity and reproductive health should be considered when administering a GnRHa to block puberty

Combined ovulation triggering with GnRH agonist and hCG in IVF patients

The aim of the review is to analyse the combination of a gonadotrophin releasing hormone (GnRH) agonist with a human chorionic gonadotrophin (hCG) trigger, for final oocyte maturation in in vitro fertilisation (IVF) cycles. The concept being a ''dual trigger'' combines a single dose of the GnRH agonist with a reduced or standard dosage of hCG at the time of triggering. The use of a GnRH agonist with a reduced dose of hCG in high responders demonstrated luteal phase support with improved pregnancy rates, similar to those after conventional hCG and a low risk of ovarian hyperstimulation syndrome (OHSS). The administration of a GnRH agonist and a standard hCG in normal responders, demonstrated significantly improved live-birth rates and a higher number of embryos of excellent quality, or cryopreserved embryos. The concept of the ''double trigger" represents a combination of a GnRH agonist and a standard hCG, when used 40 and 34 h prior to ovum pick-up, respectively. The use of the ''double trigger" has been successfully offered in the treatment of empty follicle syndrome and in patients with a history of immature oocytes retrieved or with low/poor oocytes yield. Further prospective studies are required to confirm the aforementioned observations prior to clinical implementation

폐경 전 유방암 환자에서 항암 치료 중 생식샘자극호르몬분비호르몬작용제의 투여 시점에 따른 난소 보호 효과

학위논문 (박사) -- 서울대학교 대학원 : 의과대학 의학과, 2020. 8. 전종관.Introduction: Gonadotropin-releasing hormone agonist (GnRHa) is used to suppress the ovaries for fertility preservation during cancer chemotherapy. However, there is an initial paradoxical flare-up phase that increases the release of gonadotropins and increase the ovarian activity. It is unknown whether or not GnRHa have ovarian protective effect if administered during this period. The aim of this study was to investigate the effect of the interval between the start of GnRHa and the start of chemotherapy on ovarian protection in patients with breast cancer. Methods: This study used the data from a prospective observational cohort study that included 136 patients with breast cancer below 40 years who received GnRHa during chemotherapy for fertility preservation. Plasma anti-Müllerian hormone (AMH) levels were measured before chemotherapy (baseline) and after chemotherapy. Subjects were divided into three groups according to the interval between the start of GnRHa and the start of chemotherapy for analysis: 1–6 days, 7–13 days, and ≥14 days. The percentage change of the post-chemotherapy AMH value to the baseline AMH (pcAMH) at each time point were compared among the three groups. Ranked analysis of covariance was used for statistical analysis, adjusted for age, body mass index (BMI), and the existence of polycystic ovaries (PCO). In addition, live birth after chemotherapy was also assessed among the three groups. Factors associated with recovery of ovarian function (AMH ≥ 1 ng/mL) at 12 months was also evaluated. Results: The median age of the patients was 32 years. There was no difference in the baseline AMH levels among the three groups (mean ± standard error, 5.0 ± 0.4 ng/ml [1–6 days], 5.3 ± 0.7 ng/ml [7–13 days], and 8.1 ± 1.3 ng/ml [≥14 days], p = 0.250). The pcAMH at 3, 6, 12, 24, and 36 months were not significantly different among the three groups (p values were 0.332, 0.732, 0.830, 0.148, and 0.393, respectively). Among 69 married women, 21 delivered (30.4%). There was no difference in the proportion of delivered women among the three groups (p = 0.680), and there was also no significant difference in the live birth among the three groups using Kaplan-Meier plot and the log rank test (p = 0.999). In multivariate analysis, young age (p = 0.024), low BMI (p = 0.013), and the existence of PCO (p = 0.015) were predictors for AMH ≥ 1 ng/mL at 12 months. Conclusion: There was no difference in the ovarian protective effect according to the difference in the timing of administration of GnRHa.배경: 보조항암화학요법은 난소의 예비능을 감소시켜 향후 임신의 가능성을 낮추고, 폐경을 앞당기는 부작용이 발생할 위험이 높다. 이에 대한 대비책으로 난소의 기능을 억제하는 약물을 투약하여 보조항암화학요법으로 기인하는 난소기능 저하를 방지하고자 하는 전략이 점차 널리 이용되고 있다. 이러한 전략에 사용되는 약제가 생식샘자극호르몬분비호르몬작용제이며, 이 약제는 투약 초기 수 일간 생식샘자극호르몬의 분비를 오히려 증가시키는 flare-up 현상을 특징으로 한다. 난소의 기능이 억제되지 않고 오히려 항진된 이 시기에 보조항암화학요법을 시작한 경우 난소의 보호 효과에 대해서는 현재까지 알려진 바가 없다. 본 연구의 목적은 유방암 환자에서 보조항암화학요법과 병용 투여한 생식샘자극호르몬분비호르몬작용제의 투여 시작 시점에 따른 난소 보호 효과의 차이를 파악하는 데에 있다. 방법: 서울대학교병원에서 2009년 10월부터 2016년 2월까지 유방암으로 진단받고 보조항암화학요법을 시행 받았으며, 가임력 보존을 위해 생식샘자극호르몬분비호르몬작용제를 항암제와 병용 투여한 40세 이하의 환자를 대상으로 하는 전향적 관찰적 코호트 연구이다. 난소 기능 평가를 위해 보조항암화학요법 전(기저치) 및 보조항암화학요법 종료 후에 정기적으로 검사한 항뮬러관호르몬의 혈중농도를 난소 기능의 지표로 이용하였다. 생식샘자극호르몬분비호르몬작용제의 투여 후 몇 일 후에 보조항암화학요법을 시작하였는지에 따라 대상 환자들을 1-6일, 7-13일, 14일 이상의 세 군으로 나누어 분석하였다. 항뮬러관호르몬 혈중농도 기저치 대비 항암화학요법 종료 후 항뮬러관호르몬 혈중농도 변화를 백분율로 환산하여 pcAMH라는 지표를 정의하여 세 군간의 비교를 시행하였다. 순위기반 공분산분석을 이용하여 나이, 비만도, 초음파상 다낭성난소의 유무를 보정하여 통계학적 분석을 시행하였다. 이에 더하여, 보조항암화학요법 종료 후 분만한 여성의 수를 세 군간 비교하였으며, 항암치료 종료 후 12개월에 항뮬러관호르몬의 혈중농도가 1 ng/mL 이상인 것과 관련된 인자들을 파악하기 위하여 다변수분석을 시행하였다. 결과: 대상 환자들의 나이의 중위값은 32세였다. 항뮬러관호르몬의 기저치는 세 군 간에 유의한 차이를 보이지 않았다 (평균 ± 표준오차, 5.0 ± 0.4 ng/ml [1–6일], 5.3 ± 0.7 ng/ml [7–13일], and 8.1 ± 1.3 ng/ml [≥14일 이상], p = 0.25). 항암화학요법 종료 후 pcAMH의 세 군 간 비교에서 각 평가 시점 별 p 값은 3개월 0.33, 6개월 0.73, 12개월 0.83, 24개월 0.15, 36개월 0.39로 나타났으며, 통계적으로 유의한 차이를 보이지 않았다. 혼인관계가 확인된 69명의 환자 중 총 21명의 여자가 보조항암화학요법 종료 후 생아를 출산하였다 (30.4%). 생아 출산한 여성의 비율의 비교에서 세 군 간에 유의한 차이를 보이지 않았으며(p = 0.680), 카플란-마이어 곡선 및 로그-랭크 테스트를 이용한 세 군간의 비교에서도 유의한 차이를 보이지 않았다(p = 0.999). 한편 다변수분석에서 항암화학요법 종료 후 12개월 시점에 항뮬러관호르몬 혈중농도 1 ng/mL이상의 예측인자는 젊은 나이 (p = 0.024), 낮은 비만도 (p = 0.013), 초음파상 다낭성난소가 존재하는 경우 (p = 0.015)로 확인되었다. 결론: 가임력보존 목적으로 생식샘자극호르몬분비호르몬작용제를 유방암 환자에게 보조항함화학요법과 병용투여한 경우, 생식샘자극호르몬분비호르몬작용제의 투여 시점에 따른 난소의 보호 효과의 유의한 차이가 관찰되지 않았다. 본 연구의 결과에 따르면 생식샘자극호르몬분비호르몬작용제의 투약 초기 flare-up시기에 투약한 경우에도 난소의 보호효과에는 차이가 없었다.I. Introduction 1 II. Materials and Methods 5 II-1. Study population and participants 5 II-2. Statistical analysis 8 II-3. Ethics statement 9 III. Results 10 IV. Discussion 39 V. Conclusion 47 VI. Bibliography 48 국문 초록 57Docto

Uterine Arteriovenous Malformation As A Rare Cause Of Menorrhagia

Uterine arterio venous malformation is uncommon cause of menorrhagia. We report a rare case of arteriovenous malformation diagnosed after 18 years of suffering from menorrhagi