• Clinical and Experimental Reproductive Medicine
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• v.43 no.1
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• pp.54-57
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• 2016

Controlled ovarian hyperstimulation is one of the major steps of in vitro fertilization. The inaccessibility or non-visualization of developing follicles on transvaginal sonography (the preferred imaging method) may be misjudged as a poor response, resulting in cycle cancellation. It is necessary to scrupulously appraise proxy indicators for ovarian response, such as estradiol levels, endometrial thickness, and other individual clinical characteristics. This can prompt meticulous transabdominal ultrasound follicular monitoring and oocyte retrieval with the goal of averting cycle cancellation and improving treatment outcomes.

• 대한생식의학회:학술대회논문집
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• 2006.11a
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• pp.155-156
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• 2006

• 대한생식의학회:학술대회논문집
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• 2003.12a
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• pp.93.2-94
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• 2003

• Clinical and Experimental Reproductive Medicine
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• v.21 no.3
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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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• v.31 no.4
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• pp.225-234
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• 2004

Objectives: To evaluate the efficacy of GnRH antagonist cetrorelix in women undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) and to determine changes in serum hormone concentrations during cetrorelix administration. Methods: We performed a clinical trial on 30 patients undergoing COH with highly purified follicular stimulating hormone (HP-FSH) and gonadotropin releasing hormone antagonist (GnRHant), cetrorelix. FSH was administrated from day 2 or 3 of cycle with fixed dose and adjusted according to individual response. 0.25 mg of cetrorelix was injected daily subcutaneously from stimulation day 5 until the day of hCG administration. Daily ultrasound monitoring was performed for growing follicles and serum levels of luteinizing hormone (LH), estradiol ($E_2$) and progesterone were measured daily during cetrorelix administration. Up to 4 embryos were transferred. Results: Mean age of enrolled patients was $32.0{\pm}3.4$ years (mean $\pm$ S.D.). All of 30 patients underwent oocyte pick-up, and embryo transfer was done in 28 patients. The total and mean numbers of received oocytes were 196 and $6.5{\pm}4.7$, the number of fertilized eggs was 111, and the fertilization rate was 56.6%. Total duration of FSH administration was $9.2{\pm}2.2$ days and mean of $24.3{\pm}7.7$ ampules of HP-FSH was administered. Total duration of cetrorelix administration was $5.7{\pm}1.9$ days. Serum LH and progesterone levels were maintained in the range of $1.4{\sim}2.9\;mIU/mL$ and $0.3{\sim}0.6\;ng/mL$, which respectively reflected effective prevention of premature LH surge. Clinical pregnancies were achieved in 9 patients, and overall clinical pregnancy rate was 30.0% per oocyte retrieval, and 32.1% per embryo transfer. Conclusion: GnRH antagonist is safe and convenient for COH for IVF-ET and effective with optimal pregnancy rate.

• Clinical and Experimental Reproductive Medicine
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• v.41 no.2
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• pp.41-46
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• 2014

IVM refers to the maturation of immature oocytes in culture after their recovery from small antral follicles at the stage prior to selection and dominance. IVM requires little or no FSH in vivo and has been proposed as an alternative to conventional IVF, since it reduces the primary adverse effects caused by controlled ovarian stimulation, including the ovarian hyperstimulation syndrome. Moreover, IVM is a promising option for cases for which no standard protocol is suitable, such as FSH resistance, contraindications for ovarian stimulatory drugs, and the need for urgent fertility preservation. Recently, IVM has been used in women with regular cycles and normal ovaries. However, the pregnancy rate following IVM is suboptimal compared with that of conventional IVF, indicating that further studies to optimize the protocol and the culture conditions are warranted.

• Clinical and Experimental Reproductive Medicine
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• v.17 no.1
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• pp.29-44
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• 1990

In 105 patients with the past history of poor response to the previous controlled ovarian hyperstimulation(COH) due to poor follicular growth or premature LH surge, the effectiveness of pituitary suppression with gonadotropin-releasing hormone agonist(GnRH agonist) in IVF/GIFT program was evaluated in 112 cycles of COH using a combination regimen of Leuprolide acetate (Lupron TAP Pharmaceuticals, USA) and FSH/hMG or pure FSH from May to December, 1989 at SNUH. Starting on day 21 of the menstrual cycle(MCD #21, Day 1), Lupron (1.0mg/day, subcutaneous) was administered once a day till next MCD #3(suppression phase). After the confirmation of pituitary suppression, ovarian follicular growth was stimulated with FSH/hMG or pure FSH from MCD #3(Day + 1), and Lupron was continued with hMG or FSH until hCG administration (D 0) (stimulation phase). After suppression phase, serum E2 level decreased from 183.7${\pm}$95.1(Day 1) to 17.4${\pm}$12.3pg/ml (Day +1), and serum progesterone level from 19.17${\pm}$8.67 to 0.12${\pm}$0.05ng/ml. But there was no decresas in serum LH and FSH levels; LH from 12.74${\pm}$6.21 to 15.49${\pm}$4.93mIU/ml,FSH from 7.60${\pm}$3.84 to 8.58${\pm}$3.15 rnlU/ml. There was no occurrence of premature LH surge during COH. Eleven cycles(9.8%) were cancelled due to poor follicular growth during stimulation phase, and 3 cycles (3.0%) failed in the transvaginal oocytes fretrieval. Serum E2 level was 1366.8${\pm}$642.4 on D 0 and 1492.3${\pm}$906.9pg/ml on D+1. 7.00${\pm}$3.32 follicles(FD${\geq}$12mm) were observed on D 0, and 6.11${\pm}$4.15 oocytes were retrieved, with the oocyte retrieval rate per follicle of 95.0%. 3.59${\pm}$2.57 oocytes were fertilized and cleaved with the oocyte cleavage rate of 55.7%. In 83 IVF patients, 4.08${\pm}$2.39 embryos were transferred, and 16 pregnancies were obtained with the pregnancy rate per ET 2.39 mebryos were transferred, and 16 pregnancies were obtained with the pregnancy rate per ET of 19.3%. In 6 GIFT patients, 7.83${\pm}$3.31 oocytes were retrieved and transferred with maximum number of 6, but no pregnancy was obtained. When compared with the previous 108 cycles of COH using FSH/hMG or pure FSH regimen, the cancellation rate during COH was significantly decreased, and all the parameters of the outcome of COH including the pregnancy rate were increased. These data suggest that GnRH agonist therapy for pituitary suppression is an effective adjunct to the current gonadotropin regimens for COH in IVF/GIFT and can increase the probability of oocytes retrieval and pregnancy, especially in the previous poor responders.

• Clinical and Experimental Reproductive Medicine
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• v.40 no.2
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• pp.83-89
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• 2013

Objective: To investigate outcomes of stimulated IVF cycles in which GnRH antagonist was omitted on the ovulation triggering day. Methods: A total of 86 women who underwent controlled ovarian hyperstimulation with recombinant FSH and GnRH antagonist flexible multiple-dose protocols were recruited and prospectively randomized into the conventional group (group A) or cessation group (group B). The GnRH antagonist, 0.25 mg/day of cetrorelix, was started when the leading follicle reached 14 mm in diameter and was continuously administered until the hCG triggering day (group A, 43 cycles) or until the day before hCG administration (group B, 43 cycles). The maturity of oocytes, fertilization rate, embryo quality, and implantation and clinical pregnancy rates were evaluated. Results: The duration of ovarian stimulation, total dose of gonadotropins, serum estradiol levels on hCG administration day, and number of oocytes retrieved were not significantly different between the two groups. The total dose of GnRH antagonist was significantly lower in group B than group A ($2.5{\pm}0.9$ vs. $3.2{\pm}0.8$ ampoules, p<0.05). There was no premature luteinization in any of the subjects. The proportion of mature oocytes and fertilization rate were not significantly different in group B than group A (70.7% vs. 66.7%; 71.1% vs. 66.4%, respectively). There were no significant differences in the implantation or clinical pregnancy rates. Conclusion: Our prospective randomized study suggested that cessation of GnRH antagonist on the hCG administration day during a flexible multiple-dose protocol could reduce the total dose of GnRH antagonist without compromising its effects on pregnancy rates.

• Clinical and Experimental Reproductive Medicine
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• v.32 no.4
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• pp.315-324
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• 2005

Objectives: To compare the efficacy of GnRH antagonist multiple dose protocol (MDP) with that of GnRH agonist long protocol (LP) in controlled ovarian hyperstimulation for in vitro fertilization in patients with high basal FSH (follicle stimulating hormone) level or old age, a retrospective analysis was done. Methods: Two hundred ninety four infertile women (328 cycles) who were older than 41 years of age or had elevated basal FSH level (> 8.5 mIU/mL) were enrolled in this study. The patients had undergone IVF-ET after controlled ovarian hyperstimulation using GnRH antagonist multiple dose protocol (n=108, 118 cycles) or GnRH agonist long protocol (n=186, 210 cycles). The main outcome measurements were cycle cancellation rate, consumption of gonadotropins, the number of follicles recruited and total oocytes retrieved. The number of fertilized oocytes and transferred embryos, the clinical pregnancy rates, and the implantation rates were also reviewed. And enrolled patients were divided into three groups according to their age and basal FSH levels; Group A - those who were older than 41 years of age, Group B - those with elevated basal FSH level (> 8.5 mIU/mL) and Group C - those who were older than 41 years of age and with elevated basal FSH level (> 8.5 mIU/mL). Poor responders were classified as patients who had less than 4 retrieved oocytes, or those with $E_2$ level <500 pg/mL on the day of hCG injection or those who required more than 45 ampules of exogenous gonadotropin for stimulation. Results: The cancellation rate was lower in the GnRH antagonist group than in GnRH agonist group, but not statistically significant (6.8% vs. 9.5%, p=NS). The amount of used gonadotropins was significantly lower in GnRH antagonist group than in agonist group ($34.8{\pm}11.3$ ampules vs. $44.1{\pm}13.4$ ampules, p<0.001). The number of follicles > 14 mm in diameter was significantly higher in agonist group than in antagonist group ($6.7{\pm}4.6$ vs. $5.0{\pm}3.4$, p<0.01). But, there were no significant differences in clinical pregnancy rate (24.5% in antagonist group vs. 27.4% in agonist group, p=NS) and implantation rate (11.4% in antagonist group vs. 12.0% in agonist group, p=NS) between two groups. Mean number of retrieved oocytes was significantly higher in GnRH agonist LP group than in GnRH antagonist MDP group ($5.4{\pm}3.5$ vs. $6.6{\pm}5.0$, p<0.0001). But, the number of mature and fertilized oocytes, and the number of good quality (grade I and II) and transferred embryos were not different between two groups. In each group A, B, and C, the rate of poor response did not differ according to stimulation protocols. Conclusions: In conclusion, for infertile women expected poor ovarian response such as who are old age or has elevated basal FSH level, a protocol including a controlled ovarian hyperstimulation using GnRH antagonist appears at least as effective as that using a GnRH agonist, and may offer the advantage of reducing gonadotropin consumption and treatment period. However, much work remains to be done in optimizing the GnRH antagonist protocols and individualizing these to different cycle characteristics.

• Clinical and Experimental Reproductive Medicine
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• v.42 no.4
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• pp.131-135
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• 2015

The thyroid hormones act on nearly every cell in the body. Moreover, the thyroid gland continuously interacts with the ovaries, and the thyroid hormones are involved in almost all phases of reproduction. Thyroid dysfunctions are relatively common among women of reproductive age, and can affect fertility in various ways, resulting in anovulatory cycles, high prolactin levels, and sex hormone imbalances. Undiagnosed and untreated thyroid disease can be a cause of subfertility. Subclinical hypothyroidism (SCH), also known as mild thyroid failure, is diagnosed when peripheral thyroid hormone levels are within the normal reference laboratory range, but serum thyroid-stimulating hormone levels are mildly elevated. Thyroid autoimmunity (TAI) is characterized by the presence of anti-thyroid antibodies, which include anti-thyroperoxidase and anti-thyroglobulin antibodies. SCH and TAI may remain latent, asymptomatic, or even undiagnosed for an extended period. It has also been demonstrated that controlled ovarian hyperstimulation has a significant impact on thyroid function, particularly in women with TAI. In the current review, we describe the interactions between thyroid dysfunctions and subfertility, as well as the proper work-up and management of thyroid dysfunctions in subfertile women.