• Clinical and Experimental Reproductive Medicine
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• v.48 no.1
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• pp.1-10
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• 2021

In Korean women, a westernized lifestyle is associated with an increased risk of breast cancer. Fertility preservation has become an increasingly important issue for women with breast cancer, in accordance with substantial improvements in survival rate after cancer treatment. The methods of controlled ovarian hyperstimulation (COH) for fertility preservation in breast cancer patients have been modified to include aromatase inhibitors to reduce the potential harm associated with increased estradiol levels. Random-start COH and dual ovarian stimulation are feasible options to reduce the total duration of fertility preservation treatment and to efficiently collect oocytes or embryos. Using a gonadotropin-releasing hormone agonist as a trigger may improve cycle outcomes in breast cancer patients undergoing COH for fertility preservation. In young breast cancer patients with BRCA mutations, especially BRCA1 mutations, the possibility of diminished ovarian reserve may be considered, although further studies are necessary. Herein, we review the current literature on the practical issues surrounding COH for fertility preservation in women with breast cancer.

• Clinical and Experimental Reproductive Medicine
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• v.43 no.2
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• pp.112-118
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• 2016

Objective: Ovarian reserve tests are commonly used to predict ovarian response in infertile patients undergoing ovarian stimulation. Although serum markers such as basal follicle-stimulating hormone (FSH) or random $anti-M{\ddot{u}}llerian$ hormone (AMH) level and ultrasonographic markers (antral follicle count, AFC) are good predictors, no single test has proven to be the best predictor. In this study, we developed appropriate equations and novel nomograms to predict the number of oocytes that will be retrieved using patients' age, serum levels of basal FSH and AMH, and AFC. Methods: We analyzed a database containing clinical and laboratory information of 141 stimulated in vitro fertilization (IVF) cycles performed at a university-based hospital between September 2009 and December 2013. We used generalized linear models for prediction of the number of oocytes. Results: Age, basal serum FSH level, serum AMH level, and AFC were significantly related to the number of oocytes retrieved according to the univariate and multivariate analyses. The equations that predicted the number of oocytes retrieved (log scale) were as follows: model (1) $3.21-0.036{\times}(age)+0.089{\times}(AMH)$, model (2) $3.422-0.03{\times}(age)-0.049{\times}(FSH)+0.08{\times}(AMH)$, model (3) $2.32-0.017{\times}(age)+0.039{\times}(AMH)+0.03{\times}(AFC)$, model (4) $2.584-0.015{\times}(age)-0.035{\times}(FSH)+0.038{\times}(AMH)+0.026{\times}(AFC)$. model 4 showed the best performance. On the basis of these variables, we developed nomograms to predict the number of oocytes that can be retrieved. Conclusion: Our nomograms helped predict the number of oocytes retrieved in stimulated IVF cycles.

• Clinical and Experimental Reproductive Medicine
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• v.45 no.1
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• pp.31-37
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• 2018

Objective: To evaluate the pregnancy rate and time to pregnancy after timed coitus with or without superovulation in infertile young women younger than 35 years old with low serum $anti-M{\ddot{u}}llerian$ hormone (AMH) levels ( < 25th percentile). Methods: A total of 202 patients younger than 35 years old were recruited retrospectively between 2010 and 2012. Ninety-eight women had normal serum AMH levels (25-75th percentile), 75 women had low serum AMH levels (5th ${\leq}$ & < 25th percentile) and 29 women had very low serum AMH levels ( < 5th percentile), according to reference values for their age group. Results: The clinical pregnancy rate was positively associated with AMH levels, but this trend did not reach statistical significance (43.9% vs. 41.3% vs. 27.6% in the normal, low, and very low AMH groups, respectively). The time to pregnancy was longer in the very low AMH group than in the normal AMH group ($13.1{\pm}10.9months$ vs. $6.9{\pm}6.1months$, p= 0.030). The cumulative live birth rate over 18 months was lower in the very low AMH group than in the normal AMH group, with marginal significance (20.0% vs. 55.9%, p= 0.051). The duration of infertility was negatively correlated with achieving pregnancy (odds ratio, 0.953; 95% confidence interval, 0.914-0.994; p= 0.026). Conclusion: Conservative management, such as timed coitus with or without superovulation, should be considered in young patients who have low ovarian reserve without any infertility factors. However, for women with a long duration of infertility or very low serum AMH levels, active infertility treatment should be considered.

• The Journal of Korean Medicine
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• v.43 no.1
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• pp.136-153
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• 2022

Objectives: The aim of this study was to find out whether east asian herbal medicine (EAHM) treatment alone is effective in improving pregnancy-related indicators compared to conventional medicine in women with Diminished Ovarian Reserve (DOR). Methods: We searched eligible studies from PubMed, Cochrane Library, EMBASE, Chinese National Knowledge Infrastructure Database, CiNii, Korean Medical Database, Korean Studies Information Service System, Oriental Medicine Advanced Searching Integrated System, ScienceOn. GRADE pro was used to evaluate the current evidence of the study. Result: A total of 5 studies, 325 women with DOR were included. EAHM showed a significant effect on improvement of pregnancy rate (n=270, RR 2.13 [95% CI 1.44 to 3.15], Z=3.78, p=0.0002, I2=0%) and Anti-Mullerian Hormone (AMH) level (n=211, SMD 0.82 [95% CI 0.40 to 1.25], Z=3.80, p=0.0001) compared to conventional medicine. In ovulation rate (n=156, RR 0.86 [95% CI 0.70 to 1.06], Z=1.43, p=0.15, I2=0%), Antral Follicle Count (n=245, SMD 0.27 [95% CI -0.25 to 0.79], Z=1.01, p=0.31), and follicle stimulating hormone (n=245, SMD 0.29 [95% CI -0.13 to 0.70], Z=1.36, p=0.17) level, EAHM showed similar effects to conventional medicine. In this study, the most frequently used herbal medicines were Cuscutae Semen, Dipsaci Radix, and Angelicae Gigantis Radix. Conclusion: This meta-analysis showed that EAHM could improve pregnancy rates and AMH levels in women with DOR. However, more well-designed RCTs will have to be performed further in the future.

• Clinical and Experimental Reproductive Medicine
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• v.50 no.1
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• pp.1-11
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• 2023

In reproduction, mitochondria produce bioenergy, help to synthesize biomolecules, and support the ovaries, oogenesis, and preimplantation embryos, thereby facilitating healthy live births. However, the regulatory mechanism of mitochondria in oocytes and embryos during oogenesis and embryo development has not been clearly elucidated. The functional activity of mitochondria is crucial for determining the quality of oocytes and embryos; therefore, the underlying mechanism must be better understood. In this review, we summarize the specific role of mitochondria in reproduction in oocytes and embryos. We also briefly discuss the recovery of mitochondrial function in gametes and zygotes. First, we introduce the general characteristics of mitochondria in cells, including their roles in adenosine triphosphate and reactive oxygen species production, calcium homeostasis, and programmed cell death. Second, we present the unique characteristics of mitochondria in female reproduction, covering the bottleneck theory, mitochondrial shape, and mitochondrial metabolic pathways during oogenesis and preimplantation embryo development. Mitochondrial dysfunction is associated with ovarian aging, a diminished ovarian reserve, a poor ovarian response, and several reproduction problems in gametes and zygotes, such as aneuploidy and genetic disorders. Finally, we briefly describe which factors are involved in mitochondrial dysfunction and how mitochondrial function can be recovered in reproduction. We hope to provide a new viewpoint regarding factors that can overcome mitochondrial dysfunction in the field of reproductive medicine.

• Clinical and Experimental Reproductive Medicine
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• v.50 no.4
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• pp.285-291
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• 2023

Objective: Infertility can result from a diminished ovarian reserve, but a potential remedy exists in the form of platelet-rich plasma (PRP) administration. This treatment involves both biological factors and tissue trauma mechanisms, which stimulate folliculogenesis, making it a promising and effective strategy. We assessed the impact of direct PRP injections into the ovaries on the fertility outcomes of women classified as poor responders. Methods: A quasi-experimental study was conducted from April 2021 to December 2022, focusing on patients classified as POSEIDON grade 3 or 4. PRP injections were administered into both ovaries. After 3 months, data were collected on anti-Mullerian hormone (AMH) level, follicle-stimulating hormone (FSH) level, and the numbers of oocytes, mature oocytes, and good-quality embryos following ovarian stimulation. We then compared the data from before and after PRP injection. Results: This study included 50 women, with a mean of 39 years (interquartile range [IQR], 35 to 43) and 4 years (IQR, 2 to 6) for age and infertility duration, respectively. FSH levels decreased after treatment, while AMH levels and the numbers of oocytes, metaphase II oocytes, and high-quality embryos increased. However, only the increase in high-quality embryos was significant. The pregnancy and spontaneous pregnancy rates were 20% and 14%, respectively. Notably, women with secondary infertility exhibited a significantly higher pregnancy rate than those with primary infertility. Conclusion: Ample evidence suggests that PRP can enhance ovarian function. However, further studies are needed to identify the appropriate candidates for this procedure, establish the optimal PRP preparation method, and standardize the procedure for its adjuvant use in assisted reproductive technology cycles.

• Clinical and Experimental Reproductive Medicine
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• v.51 no.2
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• pp.158-162
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• 2024

Objective: The aim of this study was to compare the outcomes of in vitro fertilization (IVF) in patients with a poor ovarian response who used methyltestosterone, versus those using a placebo, in an infertility clinic setting. Methods: This clinical trial included 120 women who had undergone IVF with intracytoplasmic sperm injection due to poor ovarian reserve and infertility. The study took place at the Yas Infertility Center in Tehran, Iran, between January 1, 2018 and January 1, 2019. In the intervention group, 25 mg of methyltestosterone was administered daily for 2 months prior to the initiation of assisted reproductive treatment. The control group was given placebo tablets for the same duration before starting their cycle. Each group was randomly assigned 60 patients. All analyses were performed using SPSS ver. 23 (IBM Corp.). Results: The endometrial thickness in the intervention group was 7.57±1.22 mm, whereas in the control group, it was 7.11±1.02 (p=0.028). The gonadotropin number was significantly higher in the control group (64.7±13.48 vs. 57.9±9.25, p=0.001). However, there was no significant difference between the two groups in the antral follicular count. The chemical and clinical pregnancy rates in the intervention group were 18.33% and 15% respectively, compared to 8.33% and 6.67% in the control group. The rate of definitive pregnancy was marginally higher in the intervention group (13.3% vs. 3.3%, p=0.05). Conclusion: The findings of this study suggest that pretreatment with methyltestosterone significantly increases endometrium thickness and is associated with an increase in the definitive pregnancy rate.

• Clinical and Experimental Reproductive Medicine
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• v.23 no.3
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• pp.283-292
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• 1996

Objective: To determine the cutoff value of clomiphene citrate challenge test(CCCT) that can predict the normal and abnormal(diminished) ovarian response group and to assess the usefulness of CCCT as a predictor of ovarian reserve. Materials and Methods: From March 1994 to Februry 1996, CCCT was performed to 129 infertile patients and among them, 20 patients whose basal FSH on the third day of menstrual cycle was more than 20 mIU/ml were excluded. At the same time, the same CCCT was performed to the fifteen healthy volunteers with proven fertility to determine the cutoff value of CCCT. Results; 1) A FSH value higher than 23.4 mIU/ml, measured on the 10th day of menstrual cycle, was defined as a abnormal ovarian response. The cutoff value of 23.4 mIU/ml is more than 2 standard deviations(SD) above the mean value of 15 healthy women after CCCT. 2) The abnormal CCCT group, the subpopulation with a FSH value of 23.4 mIU/ml or more, was 7.3%(8/109) and their mean age was higher than the normal CCCT group($36.5{\pm}4.5$ vs. $32.9{\pm}4.8$, P = 0.059). And the percentage of the patients older than 35 years of the abnormal CCCT group was significantly higher than that of the normal CCCT group(62.5% vs. 38.6%, p <0.05). 3) There was no correlation between the hormone values of the third day and the 10th day of menstrual cycle before and after CCCT except between FSH of the third day and the 10th day. Conclusion: The CCCT is a good method to predict the individual ovarian response to COH for ART, especially in the patients who has no other abnormal findings that predict poor prognosis. And it is neccessary to determine the cutoff value of CCCT by the large numbers of randomized study, and combining the previously proven prognostic factors, it can be applicated in many individual centers for evaluate the ovarian response before ART program.

• Clinical and Experimental Reproductive Medicine
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• v.26 no.2
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• pp.163-170
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• 1999

Objectives: The aims of this study are 1) to determine if GAST is a better indicator in predicting ovarian response to COH compared with patient's age or basal FSH level and 2) to evaluate its role in detecting abnormal ovarian response. Design: Prospective study in 118 patients undergoing IVF-ET using GnRH-a short protocol during May-September 1995. Materials and Methods: After blood sampling for basal FSH and estradiol $(E_2)$ on cycle day two, 0.5ml (0.525mg) GnRH agonist ($Suprefact^{(r)}$, Hoechst) was injected subcutaneously. Serum $E_2$ was measured 24 hours later. Initial $E_2$ difference $({\Delta}E_2)$ was defined as the change in $E_2$ on day 3 over the baseline day 2 value. Sixteen patients with ovarian cyst or single ovary or incorrect blood collection time were excluded from the analysis. The patients were divided into three groups by ${\Delta}E_2$; group A (n=30):${\Delta}E_2$<40 pg/ml, group B (n=52): 40 pg/ml${\leq}{\Delta}E_2$<100 pg/ml, group C (n=20): ${\Delta}E_2{\leq}100$ pg/ml. COH was done by GnRH agonist/HMG/hCG and IVF-ET was followed. Ratio of $E_2$ on day of hCG injection over the number of ampules of gonadotropins used ($E_2hCGday$/Amp) was regarded as ovarian responsiveness. Poor ovarian response and overstimulation were defined as $E_2$ hCGday less than 600 pg/ml and greater than 5000 pg/ml, respectively. Results: Mean age $({\pm}SEM)$ in group A, B and C were $33.7{\pm}0.8^*,\;31.5{\pm}0.6\;and\;30.6{\pm}0.5^*$, respectively ($^*$: p<0.05). Mean basal FSH level of group $A(11.1{\pm}1.1mlU/ml)$ was significantly higher than those of $B(7.4{\pm}0.2mIU/ml)$ and C $(6.8{\pm}0.4mIU/ml)$ (p<0.001). Mean $E_2hCGday$ of group A was significantly lower than those of group B or C, i.e., $1402.1{\pm}187.7pg/ml,\;3153.2{\pm}240.0pg/ml,\;4078.8{\pm}306.4pg/ml$ respectively (p<0.0001). The number of ampules of gonadotropins used in group A was significantly greater than those in group B or C: $38.6{\pm}2.3,\;24.2{\pm}1.1\;and\;18.5{\pm}1.0$ (p<0.0001). The number of oocytes retrieved in group A was significantly smaller than those in group B or C: $6.4{\pm}1.1,\;15.5{\pm}1.1\;and\;18.6{\pm}1.6$, respectively (p<0.0001). By stepwise multiple regression, only ${\Delta}E_2$ showed a significant correlation (r=0.68, p<0.0001) with $E_2HCGday$/Amp, while age or basal FSH level were not significant. Likewise, only ${\Delta}E_2$ correlated significantly with the number of oocytes retrieved (r=0.57, p<0.001). All four patients whose COH was canceled due to poor ovarian response belonged to group A only (Fisher's exact test, p<0.01). Whereas none of 30 patients in group A (0%) had overstimulation, 14 patients among 72 patients (19.4%) in group B and C had overstimulation (Fisher's exact test, p<0.01). Conclusions: These data suggest that initial $E_2$ difference after GAST may be a better prognostic indicator of ovarian response to COH than age or basal FSH level. Since initial $E_2$ difference demonstrates significant association with abnormal ovarian response such as poor ovarian response necessitating cycle cancellation or overstimulation, GAST may be helpful in monitoring and consultation of patients during COH in IVF-ET cycle.

• Clinical and Experimental Reproductive Medicine
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• v.35 no.3
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• pp.213-221
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• 2008

Objective: To evaluate predictor of IVF outcomes following single embryo transfer in patients with decreased ovarian reserve. Methods: A retrospective review was performed in 919 IVF cycles with elevated basal serum FSH (${\geq}12\;mIU/mL$), the number of retrieved oocytes ${\geq}4$ and serum $E_2$ concentration on hCG day <500 pg/ml between Jan. 1996 and Dec. 2006. Two hundred thirty five IVF cycles following single embryo transfer were included. Pregnancy rates and live birth rates was evaluated according to maternal age, serum $E_2$ on hCG day, basal FSH level, the number of blastomere on day 3 ET, stimulation protocol, the number of cycles of ET. Statistical analysis was used SPSS 12.0 program. Results: OPU cancellation rates were 25.6% (235 cycles), OPU failure rates were 18.5% (170 cycles), embryo transfer cancellation rates were 14.0% (129 cycles). Pregnancy rates following single embryo transfer was 8.1% (19 cycles) and live birth rates was 4.7% (11 cycles). Pregnancy rates and live birth rates of women under 35 years old was statistically higher than those of women above 35 years old (20% vs. 3.5% (p<0.0001), 12.3% vs. 1.8%, (p=0.002)). There was no difference in basal FSH, serum $E_2$ on hCG day, and the number of blastomere on ET, and stimulation protocol. Cumulative pregnancy rates according to the number of cycles of ET were $1^{st}$ 8.1%, $2^{nd}$ 9.2%, $3^{rd}$ 9.7%, $4^{th}$ 9.0%, and $5^{th}$ 9.5%. Conclusion: Pregnancy rates and live birth rates of IVF-ET cycles following single embryo transfer in patients with decreased ovarian reserve are statistically increased in women under 35 yrs old. There is no difference in cumulative pregnancy rates. These data may be helpful for counseling women with decreased ovarian reserve in attempting IVF with their own eggs or when choosing donor oocytes.