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Spontaneous ovarian hyperstimulation syndrome following a thawed embryo transfer cycle.

Mi Kyoung KIM ; Hyung Jae WON ; Sung Han SHIM ; Dong Hyun CHA ; Tae Ki YOON

Clinical and Experimental Reproductive Medicine.2014;41(3):140-145. doi:10.5653/cerm.2014.41.3.140

This article reports a case of spontaneous ovarian hyperstimulation syndrome (OHSS) following a thawed embryo transfer cycle. OHSS, a potentially life-threatening condition, is an iatrogenic complication of controlled ovarian stimulation; therefore, it is very important to prevent and treat OHSS during treatment with ovulation-inducing agents. Despite our efforts to prevent OHSS, in this case, severe spontaneous OHSS occurred, which resulted in uncontrolled preterm labor and a preterm delivery and also persisted for 6 weeks after delivery. Freezing all embryos cannot entirely prevent the development of OHSS because OHSS can occur spontaneously. Although spontaneous OHSS remains a rare event, females with a history of OHSS may have an elevated risk for spontaneous OHSS. We suggest closely monitoring cases of pregnancy following thawed embryo transfer for early diagnosis of spontaneous OHSS and the use of conservative management.
Cryopreservation ; Early Diagnosis ; Embryo Transfer* ; Embryonic Structures ; Female ; Fertilization in Vitro ; Freezing ; Humans ; Obstetric Labor, Premature ; Ovarian Hyperstimulation Syndrome* ; Ovulation Induction ; Pregnancy

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An effective method for improving outcomes in patients with a fertilization defect.

Hye Jin YOON ; Hyung Jun KIM ; In Hee BAE ; Soo Jin CHAE ; San Hyun YOON ; Won Don LEE ; Jin Ho LIM

Clinical and Experimental Reproductive Medicine.2014;41(3):137-139. doi:10.5653/cerm.2014.41.3.137

The effect of artificial oocyte activation (AOA) with a calcium ionophore on intracytoplasmic morphologically selected sperm injection (IMSI) was examined in patients with histories of repeated failed implantation attempts. Four singleton pregnancies and one twin pregnancy were obtained after embryos transfer (5/14, 35.7%). Therefore, AOA combined with IMSI can be considered an option for cycles with a fertilization defect and recurrent implantation failures.
Calcium ; Embryonic Structures ; Fertilization* ; Humans ; Oocytes ; Pregnancy ; Pregnancy, Twin ; Spermatozoa

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Observation of sperm-head vacuoles and sperm morphology under light microscope.

Yong Seog PARK ; Sol PARK ; Duck Sung KO ; Dong Wook PARK ; Ju Tae SEO ; Kwang Moon YANG

Clinical and Experimental Reproductive Medicine.2014;41(3):132-136. doi:10.5653/cerm.2014.41.3.132

OBJECTIVE: The presence of sperm-head vacuoles has been suspected to be deleterious to the outcomes of assisted reproductive technology (ART). It is difficult to accurately distinguish morphologically abnormal sperm with vacuoles under a light microscope. This study was performed to analyze the result of the observation of sperm-head vacuoles using Papanicolaou staining under a light microscope and whether the male partner's age affects these vacuoles. METHODS: Sperm morphology with vacuoles was evaluated using Papanicolaou staining and observed under a light microscope (400x) in 980 men. The normal morphology was divided into three categories (group A, <4% of normal morphology; group B, 4%-14% of normal morphology; and group C, >14% of normal morphology). The criteria for the sperm-head vacuoles were those given in the World Health Organization manual. For the analysis of the age factor, the participants were divided into the following groups: 26-30 years, 31-35 years, 36-40 years, 41-45 years, and 46-50 years. RESULTS: The percentage of sperm-head vacuoles increased with normal sperm morphology (group A vs. groups B, C) (p<0.05). In the case of the age factor, a statistically significant difference was not observed across any of the age groups. CONCLUSION: A majority of the sperm-head vacuoles showed a statistically significant difference among normal morphology groups. Therefore, we should consider the probability of the percentage of sperm-head vacuoles not increasing with age but with abnormal sperm morphology. A further study is required to clarify the effect of the sperm-head vacuoles on ART outcomes.
Age Factors ; Humans ; Male ; Reproductive Techniques, Assisted ; Semen Analysis ; Spermatozoa* ; Vacuoles* ; World Health Organization

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Relationship between reactive oxygen species and autophagy in dormant mouse blastocysts during delayed implantation.

Hyejin SHIN ; Soyoung CHOI ; Hyunjung Jade LIM

Clinical and Experimental Reproductive Medicine.2014;41(3):125-131. doi:10.5653/cerm.2014.41.3.125

OBJECTIVE: Under estrogen deficiency, blastocysts cannot initiate implantation and enter dormancy. Dormant blastocysts live longer in utero than normal blastocysts, and autophagy has been suggested as a mechanism underlying the sustained survival of dormant blastocysts during delayed implantation. Autophagy is a cellular degradation pathway and a central component of the integrated stress response. Reactive oxygen species (ROS) are produced within cells during normal metabolism, but their levels increase dramatically under stressful conditions. We investigated whether heightened autophagy in dormant blastocysts is associated with the increased oxidative stress under the unfavorable condition of delayed implantation. METHODS: To visualize ROS production, day 8 (short-term dormancy) and day 20 (long-term dormancy) dormant blastocysts were loaded with 1-microM 5-(and-6)-chloromethyl-2', 7'-dichlorodihydrofluorescein diacetate, acetyl ester (CM-H2DCFDA). To block autophagic activation, 3-methyladenine (3-MA) and wortmannin were used in vivo and in vitro, respectively. RESULTS: We observed that ROS production was not significantly affected by the status of dormancy; in other words, both dormant and activated blastocysts showed high levels of ROS. However, ROS production was higher in the dormant blastocysts of the long-term dormancy group than in those of the short-term group. The addition of wortmannin to dormant blastocysts in vitro and 3-MA injection in vivo significantly increased ROS production in the short-term dormant blastocysts. In the long-term dormant blastocysts, ROS levels were not significantly affected by the treatment of the autophagy inhibitor. CONCLUSION: During delayed implantation, heightened autophagy in dormant blastocysts may be operative as a potential mechanism to reduce oxidative stress. Further, ROS may be one of the potential causes of compromised developmental competence of long-term dormant blastocysts after implantation.
Animals ; Autophagy* ; Blastocyst* ; Estrogens ; Mental Competency ; Metabolism ; Mice* ; Oxidative Stress ; Reactive Oxygen Species*

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Interaction between thyroglobulin and ADAMTS16 in premature ovarian failure.

Jung A PYUN ; Sunshin KIM ; Kyubum KWACK

Clinical and Experimental Reproductive Medicine.2014;41(3):120-124. doi:10.5653/cerm.2014.41.3.120

OBJECTIVE: The aim of the present study was to examine whether interactions between polymorphisms in the thyroglobulin and ADAM metallopeptidase with thrombospondin type 1 motif, 16 (ADAMTS16) genes are associated with the development of premature ovarian failure (POF). METHODS: A total of 75 patients with POF and 196 controls were involved in this study. We used a GoldenGate assay to genotype single nucleotide polymorphisms (SNPs). Logistic regression analysis was performed to identify POF-associated polymorphisms and synergistic interactions between polymorphisms in the thyroglobulin and ADAMTS16 genes. RESULTS: Single gene analyses using logistic regression analysis showed no significant association between polymorphisms in the two genes and POF. In the results from interaction analyses, we found seven synergistic interactions between the polymorphisms in thyroglobulin and ADAMTS16, although there was no combination showing p-values lower than the significant threshold using the Bonferroni correction. When the AG genotype was present at the rs853326 missense SNP, the A and G alleles at the tagging SNPs rs16875268 and rs13168665 showed significant interactions (odds ratios=5.318 and 16.2 respectively; 95% confidence intervals, 1.64-17.28 and 2.08-126.4; p=0.0054 and 0.0079). CONCLUSION: Synergistic interactions between polymorphisms in the thyroglobulin and ADAMTS16 genes were associated with an increased risk of POF development in Korean women.
Alleles ; Female ; Genotype ; Humans ; Logistic Models ; Polymorphism, Single Nucleotide ; Primary Ovarian Insufficiency* ; Thrombospondins ; Thyroglobulin*

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Vitrification solution without sucrose for cryopreservation in mouse blastocysts.

Jong Kil JOO ; Young Ju LEE ; Ju Eun JEONG ; Seung Chul KIM ; Gyoung Rae KO ; Kyu Sup LEE

Clinical and Experimental Reproductive Medicine.2014;41(3):115-119. doi:10.5653/cerm.2014.41.3.115

OBJECTIVE: This study was designed to investigate the survival rate of vitrified mouse blastocysts depending on the presence or absence of sucrose in vitrification solution. METHODS: Mouse two-cell embryos were collected and cultured to blastocysts. Two vitrification solutions were prepared. The control solution was composed of 25% glycerol, 25% ethylene glycol, and 0.5 M sucrose (G25E250.5S) containing 2.5 mL glycerol, 2.5 mL ethylene glycol, 2 mL SSS, and 0.855 g sucrose in 5 mL PB1. The experimental solution was composed of 25% glycerol and 25% ethylene glycol (G25E25) and contained 2.5 mL glycerol and 2.5 mL ethylene glycol in 5 mL PB1. Artificial shrinkage was conducted by aspirating the blastocoelic fluid using an ICSI pipette. To examine the effect of sucrose in the vitrification solution on the survival rate of mouse blastocysts, the shrunken-equilibrated blastocysts were rehydrated or vitrified after being exposed to one of the two vitrification solutions. After exposure and the vitrification-thawing process, the re-expansion rate and hatching rate were evaluated after 6 hours of in vitro culture. RESULTS: The re-expansion rate of mouse blastocysts exposed to vitrification solution with and without sucrose were not different in the experimental solution (without sucrose) (98%) and the control solution (with sucrose) (92%) (p>0.05). The hatching rate was higher in the experimental solution (95%) than in the control solution (88%), but did not differ across two treatments (p>0.05). The re-expansion rate of mouse blastocysts vitrified in the control solution was 92% and 94%, respectively (p>0.05), and the hatching rate was higher in the experimental solution (90%) than in the control solution (74%) (p<0.05). CONCLUSION: Sucrose need not be added in vitrification solution for freezing of artificially shrunken mouse blastocysts.
Animals ; Blastocyst* ; Cryopreservation* ; Embryonic Structures ; Ethylene Glycol ; Freezing ; Glycerol ; Mice* ; Sperm Injections, Intracytoplasmic ; Sucrose* ; Survival Rate ; Vitrification*

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Empirical medical therapy in idiopathic male infertility: Promise or panacea?.

Jae Hung JUNG ; Ju Tae SEO

Clinical and Experimental Reproductive Medicine.2014;41(3):108-114. doi:10.5653/cerm.2014.41.3.108

Male factors account for 20%-50% of cases of infertility and in 25% of cases, the etiology of male infertility is unknown. Effective treatments are well-established for hypogonadotropic hypogonadism, male accessory gland infection, retrograde ejaculation, and positive antisperm antibody. However, the appropriate treatment for idiopathic male infertility is unclear. Empirical medical treatment (EMT) has been used in men with idiopathic infertility and can be divided into two categories based on the mode of action: hormonal treatment and antioxidant supplementation. Hormonal medications consist of gonadotropins, androgens, estrogen receptor blockers, and aromatase inhibitors. Antioxidants such as vitamins, zinc, and carnitines have also been widely used to reduce oxidative stress-induced spermatozoa damage. Although scientifically acceptable evidence of EMT is limited because of the lack of large, randomized, controlled studies, recent systematic reviews with meta-analyses have shown that the administration of gonadotropins, anti-estrogens, and oral antioxidants results in a significant increase in the live birth rate compared with control treatments. Therefore, all physicians who treat infertility should bear in mind that EMT can improve semen parameters and subsequent fertility potential through natural intercourse.
Androgens ; Antioxidants ; Aromatase Inhibitors ; Drug Therapy ; Ejaculation ; Estrogens ; Female ; Fertility ; Gonadotropins ; Humans ; Hypogonadism ; Infertility ; Infertility, Male* ; Live Birth ; Male ; Pregnancy ; Pregnancy Outcome ; Semen ; Semen Analysis ; Spermatozoa ; Vitamins ; Zinc

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The role of autophagy in the placenta as a regulator of cell death.

Jin Sung GONG ; Gi Jin KIM

Clinical and Experimental Reproductive Medicine.2014;41(3):97-107. doi:10.5653/cerm.2014.41.3.97

The placenta is a temporary fetomaternal organ capable of supporting fetal growth and development during pregnancy. In particular, abnormal development and dysfunction of the placenta due to cha nges in the proliferation, differentiation, cell death, and invasion of trophoblasts induce several gynecological diseases as well as abnormal fetal development. Autophagy is a catalytic process that maintains cellular structures by recycling building blocks derived from damaged microorganelles or proteins resulting from digestion in lysosomes. Additionally, autophagy is necessary to maintain homeostasis during cellular growth, development, and differentiation, and to protect cells from nutritional deficiencies or factors related to metabolism inhibition. Induced autophagy by various environmental factors has a dual role: it facilitates cellular survival in normal conditions, but the cascade of cellular death is accelerated by over-activated autophagy. Therefore, cellular death by autophagy has been known as programmed cell death type II. Autophagy causes or inhibits cellular death via the other mechanism, apoptosis, which is programmed cell death type I. Recently, it has been reported that autophagy increases in placenta-related obstetrical diseases such as preeclampsia and intrauterine growth retardation, although the mechanisms are still unclear. In particular, abnormal autophagic mechanisms prevent trophoblast invasion and inhibit trophoblast functions. Therefore, the objectives of this review are to examine the characteristics and functions of autophagy and to investigate the role of autophagy in the placenta and the trophoblast as a regulator of cell death.
Apoptosis ; Autophagy* ; Cell Death* ; Cell Differentiation ; Cellular Structures ; Digestion ; Fetal Development ; Fetal Growth Retardation ; Homeostasis ; Lysosomes ; Malnutrition ; Metabolism ; Placenta* ; Pre-Eclampsia ; Pregnancy ; Recycling ; Trophoblasts

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Pulmonary and retroperitoneal benign metastasizing leiomyoma.

Su Yeon LIM ; Joon Cheol PARK ; Jin Gon BAE ; Jong In KIM ; Jeong Ho RHEE

Clinical and Experimental Reproductive Medicine.2011;38(3):174-177. doi:10.5653/cerm.2011.38.3.174

Benign metastasizing leiomyoma (BML) is a rare disease, which usually occurs in women with a history of a prior hysterectomy or myomectomy for benign uterine leiomyoma, and has the potential to metastasize to distant sites, such as the lung, lymph nodes, muscular tissue, heart, or retroperitoneum. These lesions are slow-growing, asymptomatic, and usually found incidentally. The prognosis of BML is also excellent. However, there has been debate on the origin and the correct classification of BML, and there are no guidelines for the treatment of BML. We report here on a rare case of BML in both the retroperitoneal cavity and lung in a 48-year-old woman with a history of hysterectomy due to histologically benign uterine leiomyoma. The patient underwent retroperitoneal mass excision and bilateral salpingo-oophorectomy, and then wedge biopsy of two pulmonary nodules was performed additionally 9 days later. Until now, there has been no sign of recurrence and the patient remains asymptomatic. To our knowledge, pulmonary BML is rare and the co-existence of the retroperitoneal metastases after previous hysterectomy is even rarer.
Biopsy ; Female ; Heart ; Humans ; Hysterectomy ; Leiomyoma ; Lung ; Lymph Nodes ; Middle Aged ; Neoplasm Metastasis ; Prognosis ; Rare Diseases ; Recurrence

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The role of methylenetetrahydrofolate reductase C677T polymorphism on the peripheral blood natural killer cell proportion in women with unexplained recurrent miscarriages.

Chan Woo PARK ; Ae Ra HAN ; Joanne KWAK-KIM ; So Yeon PARK ; Jung Yeol HAN ; Mi Kyoung KOONG ; In Ok SONG ; Kwang Moon YANG

Clinical and Experimental Reproductive Medicine.2011;38(3):168-173. doi:10.5653/cerm.2011.38.3.168

OBJECTIVE: To examine the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and hyperhomocysteinemia in women with unexplained recurrent miscarriages (RM) and to investigate the association between MTHFR genotype variants and alloimmune activation, proportion of peripheral blood natural killer (pbNK) cells. METHODS: A total of 39 patients with a history of two or more unexplained miscarriages were recruited to this study. The controls were women who had a live birth without a history of RM (n=50). The proportion of pbNK cells was measured by flow cytometry. Plasma homocysteine levels and the incidence of the MTHFR variant of the RM and control groups were compared. The proportion of pbNK cells was compared to the MTHFR variants in the RM group. RESULTS: No differences were found between the two groups' mean plasma homocysteine levels (7.6+/-1.5 micromol/L vs. 7.1+/-2.1 micromol/L) or incidence of the MTHFR genotype variant (CC, 35% vs. 33%; CT, 40% vs. 53%; and TT, 25% vs. 14%). In the RM group, individuals with the TT variant (7.7+/-1.1 micromol/L) had higher homocysteine levels than those with the CC and CT variants (7.4+/-1.9 micromol/L and 7.4+/-1.2 micromol/L) and those with the CT variant (19.2+/-8.1%) had a higher proportion of CD3-/CD56+ pbNK cells than those with the CC and TT variants (17.7+/-6.6% and 17.9+/-7. 0%), but the results of both comparisons were statistically insignificant. CONCLUSION: These preliminary results show no difference in plasma homocysteine levels between the RM and control groups or among MTHFR genotype variants in the RM group, which may suggest that the plasma homocysteine level is difficult to use as a predictive marker of RM in the Korean population. A study of a larger number of patients is needed.
Abortion, Habitual ; Abortion, Spontaneous ; Female ; Flow Cytometry ; Genotype ; Homocysteine ; Humans ; Hyperhomocysteinemia ; Incidence ; Killer Cells, Natural ; Live Birth ; Methylenetetrahydrofolate Reductase (NADPH2) ; Plasma ; Pregnancy

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