• Clinical and Experimental Reproductive Medicine
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• 제40권1호
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• pp.38-41
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• 2013

Liver damage induced by ovarian stimulation has been demonstrated in some cases reported in the literature. However, there has never been a fruitful debate on this topic. The present manuscript tried to fill this gap. We reported a case of a 35-year-old nulliparous woman admitted to our obstetric emergency room for severe pre-eclampsia. She had been subjected to four cycles of controlled ovarian stimulation for intrauterine insemination. At 32 weeks of gestation, she developed severe pre-eclampsia, which led to HELLP syndrome complicated by fatal liver failure. The etiological link between ovarian stimulation and HELLP syndrome is intriguing. Further investigations are needed to understand whether repeated ovarian stimulation may represent a risk factor in pre-eclamptic patients.

• 한국발생생물학회지:발생과생식
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• 제25권4호
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• pp.213-223
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• 2021

Controlled ovarian hyperstimulation (COH) is routinely used in the in vitro fertilization and embryo transfer (IVF-ET) cycles to increase the number of retrieved mature oocytes. However, the relationship between repeated COH and ovarian function is still controversial. Therefore, we investigated whether repeated ovarian stimulation affects ovarian aging and function, including follicular development, autophagy, and apoptosis in follicles. Ovarian hyperstimulation in mice was induced by intraperitoneal injection with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG). Mice subjected to ovarian stimulation once were used as a control group and 10 times as an experimental group. Repeated injections with PMSG and hCG significantly reduced the number of primary follicles compared to a single injection. The number of secondary and antral follicles increased slightly, while the number of corpus luteum increased significantly with repeated injections. On the other hand, repeated injections did not affect apoptosis in follicles associated with follicular atresia. The expression of autophagy-related genes Atg5, Atg12, LC3B, and Beclin1, cell proliferation-related genes mTOR, apoptosis-related genes Fas, and FasL was not significantly different between the two groups. In addition, the expression of the aging-related genes Dnmt1, Dnmt3a, and AMH were also not significantly different. In this study, we demonstrated that repeated ovarian stimulation in mice affects follicular development, but not autophagy, apoptosis, aging in ovary. These results suggest that repetition of COH in the IVF-ET cycle may not result in ovarian aging, such as a decrease in ovarian reserve in adult women.

• Clinical and Experimental Reproductive Medicine
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• 제40권2호
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• pp.95-99
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• 2013

Objective: To evaluate the correlation between serum levels of anti-M$\ddot{u}$llerian hormone (AMH) and ovarian response to mild stimulation in normoovulatory women and anovulatory women with polycystic ovary syndrome (PCOS). Methods: Seventy-four cycles of mild stimulation (clomiphene citrate+gonadotropin followed by timed intercourse or intrauterine insemination) performed in normoovulatory women (57 cycles) and anovulatory women with PCOS (17 cycles). Ovarian sensitivity was defined by the number of mature follicles (${\geq}14mm$) on triggering day per 100 IU of gonadotropin. A correlation between ovarian sensitivity and the baseline serum AMH level (absolute or multiples of the median [MoM] value for each corresponding age) was calculated. Correlation between ovarian response and serum AMH level was evaluated. Results: Ovarian sensitivity to mild stimulation was positively correlated with absolute serum AMH (r=0.535, p<0.001) or AMH-MoM value (r=0.390, p=0.003) in normoovulatory women, but this correlation was not observed in anovulatory women with PCOS (r=0.105, p>0.05, r=-0.265, p>0.05, respectively). Conclusion: Ovarian response to mild stimulation is possibly predicted by the serum AMH level in normoovulatory women, but not in anovulatory women with PCOS.

• Clinical and Experimental Reproductive Medicine
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• 제38권3호
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• pp.159-163
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• 2011

Objective: To compare the IVF outcomes of mild ovarian stimulation with conventional ovarian stimulation in poor responders. Methods: From 2004 to 2009, 389 IVF cycles in 285 women showed poor responses (defined as either a basal FSH level ${\geq}$12 mIU/mL, or the number of retrieved oocytes ${\leq}$3, or serum $E_2$ level on hCG day <500 pg/mL) were analyzed, retrospectively. In total, 119 cycles with mild ovarian stimulation (m-IVF) and 270 cycles with conventional ovarian stimulation (c-IVF) were included. Both groups were divided based on their age, into groups over and under 37 years old. Results: The m-IVF group was lower than the c-IVF group in the duration of stimulation, total doses of gonadotropins used, serum $E_2$ level on hCG day, the number of retrieved oocytes, and the number of mature oocytes. However, there was no significant difference in the number of good embryos, the number of transferred embryos, the cancellation rate, or the clinical pregnancy rate. In the m-IVF group over 37 years old, the clinical pregnancy rate and live birth rate were higher when compared with the c-IVF group, but this result was not statistically significant. Conclusion: In poor responder groups, mild ovarian stimulation is more cost effective and patient friendly than conventional IVF. Therefore, we suggest that mild ovarian stimulation could be considered for poor responders over 37 years old.

• Clinical and Experimental Reproductive Medicine
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• 제29권4호
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• pp.251-258
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• 2002

Objective : The aim of this study was to evaluate the outcomes of the GnRH antagonist (Cetrotide) minimal stimulation protocol comparing with GnRH agonist combined long step down stimulation protocol in PCOS patients. Materials and Method: From Apr 2001 to May 2002, 22 patients (22 cycles) were performed in controlled ovarian hyperstimulation using by GnRH antagonist and GnRH agonist for PCOS patients. GnRH antagonist (Cetrotide) combined minimal stimulation protocol was administered in 10 patients (10 cycles, Study Group) and GnRH agonist long step down stimulation protocol was administered in 12 patients (12 cycles, Control Group). We compared the pregnancy rate/cycle, total FSH (A)/cycle, Retrieved oocyte/cycle, the incidence of ovarian hyperstimulation syndrome, multiple pregnancy rate between the two groups. Student-t test were used to determine statistical significance. Statistical significance was defined as p<0.05. Results: Group of GnRH antagonist (Cetrorelix) minimal stimulation protocol produced fewer oocytes (6.4 versus 16.3 oocytes/cycle) using a lower dose of FSH (22.2 versus 36.1 Ample/cycle) and none developed OHSS and multiple pregnancy. Although the trends were in favour of the GnRH antagonist (Cetrorelix) protocol, the differences did not reach statistical significance. This was probably due to small sample size. Conclusion: The use of GnRH antagonist reduce the risk of ovarian hyperstimulation and multiple pregnancy. We suggest that GnRH antagonist might be alternative controlled ovarian hyperstimulation method, especially in PCOS patients who will be ovarian high response.

• Clinical and Experimental Reproductive Medicine
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• 제21권3호
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• pp.241-245
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• 1994

Despite increasing success rate of IVF, poor response to ovarian stimulation remains a problem. So, attempts to improve ovarian responses, for example, by using combined gonadotropin-releasing hormone analogue(GnRH-a) and human menopausal gonadotropin(hMG) have shown limited success. It is reported that response of granulosa cells in vitro to FSH is stimulated by co-incubation with IGF-l, and IGF-l production can be increased by growth hormone. This suggest that combination regimen of G.H. and hMG may augment follicle recruitment. In fifteen patients who had previous history of poor ovarian response to gonadotropin stimulation after pituitary suppression with mid -luteal GnRH-a, the effectiveness of cotreatment with G.H. in IVF program was evaluated using a combination regimen of G.R. and hMG at Korea University Hospital IVF Clinic. Ovarian responses to gonadotropin stimulation in control and GH-treated cycles assessed by total dose and duration of hMG treatment, follicular development and peak $E_2$ level, number of eggs retrieved, and fertilization rates were also assessed. In each group, serum and follicular fluid IGF-1 concentrations on day of egg collection were measured by RIA after acidification and extraction by reveresed phase chromatography. Patients receiving G.H. required fewer days and ampules of gonadotropins, developed more oocytes, and more embryos transferred. But, the differences were not statistically significant, except the duration of hMG treatment. Our data showed a significantly higher concentration of IGF-l in the serum, not in the follicular fluid, of patients treated with G.H. compared with control group. These data suggest that growth hormone treatment does not improve the ovarian response in women with limited ovarian reserve to gonadotropin stimulation for IVF.

• Clinical and Experimental Reproductive Medicine
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• 제38권4호
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• pp.234-237
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• 2011

Objective: During stimulated IVF cycles, up to 15% of oocytes are recovered as immature. The purpose of this study was to investigate the trend of oocyte maturity in repeated ovarian stimulation for IVF. Methods: One hundred forty-eight patients were selected who underwent two consecutive IVF cycles using same stimulation protocol during 2008 to 2010. Ovarian stimulation was performed with FSH and human menopausal gonadotropin and flexible GnRH antagonist protocol in both cycles. Oocyte maturity was assessed according to presence of germinal vesicle (GV) and the first polar body. Immature oocyte was defined as GV stage or metaphase I oocyte (GV breakdown with no visible polar body) and cultured up to 48 hours. If matured, they were fertilized with ICSI. Results: Percentages of immature oocytes were 30.8% and 32.9% ($p$=0.466) and IVM rates of immature oocytes were 36.2% and 25.7% ($p$=0.077), respectively. A significant correlation was noted between percentage of immature oocytes in the two cycles (R=0.178, $p$=0.03). Women with >40% immaturity in both cycles (n=21) showed lower fertilization rate of $in$ $vivo$ matured oocytes (56.4% vs. 72.0%, $p$=0.005) and lower pregnancy rate (19.0% vs. 27.1%, $p$=0.454) after the second cycle when compared with women with <40% immaturity (n=70). In both groups, female age, number of total retrieved oocyte and embryos transferred were similar. Conclusion: In repeated ovarian stimulation cycles for IVF, the immature oocyte tended to be retrieved repetitively in consecutive IVF cycles.

• Clinical and Experimental Reproductive Medicine
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• 제37권4호
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• pp.293-305
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• 2010

난소과자극증후군은 발생 시 생명을 위협하는 심각한 의인성 합병증으로, 불임 치료를 목적으로 성선자극호르몬을 사용하여 과배란을 유도할 때 발생한다. 따라서, 과배란 유도를 하기에 앞서 위험요인을 가진 환자를 파악하여 저용량의 성선자극호르몬을 사용하거나, GnRH antagonist protocol을 이용함으로써 발생을 예방하는 것이 중요하고, 과배란 유도 중 ovarian hyperstimulation syndrome (OHSS)의 발생이 예측될 때는 성선자극호르몬 투여 시 coasting을 하고 난포 성숙을 유도할 때 저용량의 hCG 혹은 GnRH agonist를 이용하고, 중증의 OHSS가 예측될 때에는 주기취소로 OHSS의 유병기간을 줄이거나 배아동결 등을 통해 후발성 난소과자극증후군을 예방할 수 있다. 그리고, metformin과 dopamine agonist를 난소과자극증후군을 예방을 위해 고려해 볼 수 있겠다.

• 대한생식의학회:학술대회논문집
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• 대한불임학회 2001년도 제2차 연수강좌
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• pp.49-54
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• 2001

• Clinical and Experimental Reproductive Medicine
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• 제39권4호
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• pp.132-137
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• 2012

Empty follicle syndrome (EFS) is a condition in which no oocytes are retrieved after an apparently adequate ovarian response to stimulation and meticulous follicular aspiration. EFS can be classified into 'genuine' and 'false' types according to hCG levels. It is a rare condition of obscure etiology. The existence of genuine EFS has been questioned and is still controversial. The limitation around EFS is that the definition of EFS is obscure. Management of patients with EFS is a challenge to physicians. No single treatment is known to be universally effective. However, patients should be adequately informed regarding the importance of correct hCG administration because improper hCG administration is a common and preventable cause of EFS. EFS is a syndrome that deserves additional study because such investigation could lead to a further understanding of ovarian biology and infertility.