Current status of assisted reproductive technology in Korea, 2009

Great advances have been made in the field of assisted reproductive technology (ART) since the first in vitro fertilization (IVF) baby was born in Korea in the year of 1985. However, it deserve to say that the invaluable data from fertility centers may serve as a useful source to find out which factors affect successful IVF outcome and to offer applicable information to infertile patients and fertility clinics. This article intended to report the status of ART in 2009 Korean Society of Obstetrics and Gynecology surveyed. The current survey was performed to assess the status and success rate of ART performed in Korea, between January 1 and December 31, 2009. Reporting forms had been sent out to IVF centers via e-mail, and collected by e-mail as well in 2012. With International Committee Monitoring Assisted Reproductive Technologies recommendation, intracytoplasmic sperm injection (ICSI) and non-ICSI cases have been categorized and also IVF-ET cases involving frozen embryo replacement have been surveyed separately. Seventy-four centers have reported the treatment cycles initiated in the year of 2009, and had performed a total of 27,947 cycles of ART treatments. Among a total of 27,947 treatment cycles, IVF and ICSI cases added up to 22,049 (78.9%), with 45.3% IVF without ICSI and 54.7% IVF with ICSI, respectively. Among the IVF and ICSI patients, patients confirmed to have achieved clinical pregnancy was 28.8% per cycle with oocyte retrieval, and 30.9% per cycle with embryo transfer. The most common number of embryos transferred in 2009 is three embryos (40.4%), followed by 2 embryos (28.4%) and a single embryo transferred (13.6%). Among IVF and ICSI cycles that resulted in multiple live births, twin pregnancy rate was 45.3% and triple pregnancy rate was 1.1%. A total of 191 cases of oocyte donation had been performed to result in 25.0% of live birth rate. Meanwhile, a total of 5,619 cases of frozen embryo replacement had been performed with 33.7% of clinical pregnancy rate per cycle with embryo transfer. When comparing with international registry data, clinical pregnancy rate per transfer from fresh IVF cycles including ICSI (34.1%,) was comparable to clinical pregnancy rate per transfer in European Society for Human Reproduction and Embryology report was 32.5% though lower than 45.0% for USA data. There was no remarkable difference in status of assisted reproductive technology in Korea between the current report and the data reported in 2008. The age of women trying to get pregnant was reconfirmed to be the most important factor that may have impact on success of ART treatment.

Clinical Effectiveness of Urinary Human Chorionic Gonadotropin Related Protein (hCGRP) Quantification for Diagnosis of Ectopic Pregnancy

We detected pregnancy related new molecule, human chorionic gonadotropin related protein (hCGRP) in the urine of a pregnant women by using a monoclonal antibody against the human chorionic gonadotropin (hCG). This study examined the effectiveness of urinary hCGRP quantification in diagnosing ectopic pregnancy. This study included 40 normal pregnant women and 25 patients with ectopic pregnancy. Patients' serum and urinary intact whole hCG (i-hCG) and hCGRP concentrations were measured using sandwich ELISA and the ratio of hCGRP to i-hCG was calculated. Statistical analysis was performed using statistical package for social sciences (SPSS) 10.0. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the cut-off value to discriminate ectopic pregnancies from normal intrauterine pregnancies. Urinary hCGRP and hCGRP/i-hCG ratio in ectopic pregnancy group (14 +/- 6.6 ng/mL, 4.6 +/- 1.9%, respectively) were significantly lower than those of normal pregnancy group (149 +/- 10.2 ng/mL, 29.7 +/- 1.9%, respectively; p<0.001). Based on ROC curve analysis, a cut-off point of urinary hCGRP/i-hCG ratio <16.2% discriminated between ectopic pregnancy and normal pregnancy with a sensitivity, specificity, positive predictive value and negative predictive value of 92.0%, 90.0%, 32.6%, and 99.5%, respectively. Urinary hCGRP/i-hCG ratio measurement may be effective in diagnosing ectopic pregnancy.

Transcervical embryoscopy in missed abortion / 대한산부인과학회지

OBJECTIVE: Approximately 15-20% of all clinically recognized pregnancies result in spontaneous abortion and 60-70% of these are attributable to detectable chromosome abnormalities. Although the incidence of first trimester losses is high, spontaneous abortion material is often poorly described from a development perspective. The purpose of this study was to determine the usefulness of transcervical embryoscopy in diagnosing localized and generalized defects in the embryonic morphogenesis of missed abortions. The embryoscopic findings are supplemented by the results of cytogenetic analysis in all cases. METHODS: In this study, consisted of 26 women with the final diagnosis of missed abortion between August 1, 2003 and October 31, 2003 in Samsung Cheil Hospital. Prior to the instrumental evacuation of the uterus a rigid hysteroscope was passed transcervically into the amniotic cavity to obtain a detail view of the embryo. Karyotyping was done in all cases included in this study. RESULTS: Visualization of embryo or early fetus was successful in 24 cases. Among 24 examined cases, 21 cases had successful karyotype and as a result 11 (11/21, 52.4%) had abnormal karyotype. Among 21 cases which had successful karyope, 4 (4/21, 19.0%) had normal external features, 10 (10/21, 47.6%) had classified as growth-disorganized and 7 (7/21, 33.3%) had either isolated or multiple defects, including facial dysplasia, delayed limb development, facial fusion to chest, umbilical cyst, brownish discoloration of ventral part and increased nuchal thickness. Of the morphologically normal and growth-disorganized embryo in embryoscopic examination, only 1 and 4 (1/4, 25.0% and 4/10, 40.0%) had a abnormal karyotype. In contrast, of the morphologically abnormal embryo in embryoscopic examination, 5 (5/7, 71.4%) had a abnormal karyotype. CONCLUSION: Transcervical embryoscopy permits visualization of the embryo in utero, unaffected by the damage usually caused by its instrumental evacuation or spontaneous passage. This technique can be a helpful tool for understanding human embryonic malformations and genetic counseling for parents. Futhermore, correlation of morphological and cytogenetic findings in spontaneous abortion specimens could provide the need of further evaluation for future pregnancies in couples which had fear of repeated abortions. But, more larger scaled controlled study is needed for widely use of transcervical embryoscopy in missed abortion.

A Case of Ipsilateral Primary Ovarian Pregnancy After IVF-ET in a Patient with Previous Unilateral Salpingectomy / 대한산부인과학회잡지

Marcus and Brinsden have reported the first ovarian pregnancy achieved by IVT-ET in 1993. They reported seven cases of primary ovarian pregnancy from 116 ectopic pregnancies after IVF. With advancement of ART, the incidence of ectopic pregnancy is increasing, but ovarian pregnancy is still a rare complication. We report a case of ipsilateral primary ovarian pregnancy after IVF-ET with a patient with previous unilateral salpingectomy with a brief review of literature.

Effectiveness of Low Dose Aspirin and Prednisolone Supplementation for IVF-ET / 대한산부인과학회잡지

OBJECTIVE: To estimate the efficacy of low-dose aspirin and prednisolone supplementation in women undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization and embryo transfer (IVF-ET). METHODS: From 1 July 2001 to 31 July 2002, A total of 306 cycles from 306 patients who attended infertility clinic at Samsung Cheil Hospital was enrolled in this study. With pituitary desensitization in a short gonadotrophin-releasing hormone (GnRH) agonist protocol, recombinant FSH (Puregon, Organon, Netherlands) was administered for ovarian stimulation, until the largest follicle had a mean diameter > 18 mm and at least two other follicles with a diameter of 16 mm. In study group (128 cycles), low dose aspirin (100 mg/day) and prednisolone (5 mg/day) were administered from COH starting day to post-oocyte retrieval 12th day. The COH protocol of control group (178 cycles) was same as study group, except no additional supplementation. Retrospectively, we analysed ovarian response and outcome of IVF cycles. RESULTS: The demographic characteristics of two groups were not different. E2 on hCG day (2408.3+/-1375.4 pg/ml vs 2232.3+/-1305.1 pg/ml: p=0.261), number of retrieved oocytes (13.1+/-9.1 vs 12.5+/-8.8: p=0.680), number of good embryos transferred (3.0+/-2.5 vs 2.9+/-2.0) were not different significantly between two groups. hCG positive rate (52.3% vs 43.3%: p=0.116), biochemical pregnancy rate (23.9% vs 15.6%: p=0.224), clinical pregnancy rate (39.8% vs 36.5%: p=0.629), and clinical abortion rate (10.4% vs 6.5%: p=0.392) were not different significantly either. hCG positive rate (56.1% vs 44.7%: p=0.079) shows a increasing tendency in study group, younger than 35 years old. In study group, older than 36 years old or basal FSH > 10 mIU/ml, there were no significant improvement of ovarian response and prgnancy rate. CONCLUSION: Low dose aspirin and prednisolone supplementation in routine IVF patients shows no significant improvement in ovarian response, pregnancy rate, and implantation rate. Also, in poor ovarian responder, this supplementation shows no benefits.

cDNA Microarray Expression Analysis in HPV-Infected Uterine Cervical Cancer Cell Line / 대한산부인과학회잡지

OBJECTIVE: To estimate the difference in gene expression related to carcinogenesis between HPV 16 positive squamous cell carcinoma and HPV 16 positive adenocarcinoma of cervix. METHODS: We used cDNA microarray technology to identify alterations in gene expression of human cervical cancers. Gene expression of three cell lines, CaSki and SiHa (HPV 16 positive squamous cell carcinoma) and HeLa (HPV 16 positive adenocarcinoma) were compared with HT3 (HPV 16 negative squamous cell carcinoma). The microarray contains twin spots for 344 cancer-associated genes. RESULTS: The analysis showed several interesting findings: (1) In all three squamous cell lines, CD4, CSF1, MMP15 and TNFR6 were increased, whereas SLC3A2 were decreased, (2) Only in adenocarcinoma cell line HeLa, CDC25A, CDK2, CDK9, IL2, PF4, MAD, FCER2, MAP4K1 and MS4A1 were increased, and PLAU, IL8, IL9R and ATK were decreased. (3) In both squamous cell carcinoma cell lines CaSki and SiHa, 61 genes which belong to chemokine, cell cycle, growth factor, interleukin, adhesion molecule, protein kinase and TNF were increased, whereas 10 genes which are associated with apoptosis and cytokine were increased only in SiHa, and 97 genes which are associated with a variety of cell functions were increased only in CaSki. CONCLUSION: We suggest that there might be common, but also different carcinogenic mechanisms involved in HPV 16 related cervical cancers according to the histologic subtypes and different tumors.

A case of primary amenorrhea due to 17alpha- hydroxylase deficiency / 대한내과학회지

The enzyme, 17 -hydroxylase, is necessary for both cortisol and estrogen synthesis. Deficiency of the hormone results in increased adrenocorticotrophic hormone (ACTH), follicle-stimulating hormone (FSH). Synthesis of progesterone, 11-deoxycorticosterone (DOC), corticosterone and aldosterone don't require the enzyme. The lack of estrogen results in primary amenorrhea and absent sexual maturation. The replacement of dexamethasone and estrogens has lowered the blood pressure and produced feminization. A 19-year-old female had 46,XX genotype and presented amonorrhea, absence of sexual characteristics, hypertension and hypokalemia. Endocrinologic studies demonstrated increased plasma progesterone, ACTH levels and low production of 17 -hydroxyprogesterone and testosterone. We report a rare case of 17 -hydroxylase deficency with a brief history and review of the literature.

Chromosome Analysis of Abortuses in Recurrent Spontaneous Aborters with Serum Anticardiolipin Antibodies / 대한산부인과학회잡지

OBJECTIVE: It has been suggestes that various mechanism of fetal loss are associated with anticardiolipin(ACA) and humoral immunity in the patients with recurrent spontaneous abortion. Thus we have investigated the relationship between ACA and chromosomal anomaly to know the clinical impact of ACA to early fetal loss as comparing to the chromosomal anomaly in the patients of recurrent spontaneous abortions. MATERIALS AND METHODS: Patients(n=88) with a history of recurrent spontaneous abortion (2 or more) between January 1, 1994 and June 30, 1999 were included in this study. Quantitative measurement of serum ACA was performed by ELISA and chromosomal analysis of chorionic villi obtained from aborted conceptuses was done by using standard G-banding technique. RESULTS: The incidence rate of ACA positive was 27%(24/88) and that of chromosomal abnormality was 57%(50/88). The incidence rate of abnormal karyotype was 54% (13/24) in ACA positive. Among 24 ACA positive, 10 had IgG-ACA positive, 10 had IgM-ACA positive and 4 had both types of ACA. The incidence rate of chromosomal anomalies was 30% (3/10) in IgG-ACA positive, 90%(9/10) in IgM-ACA positive and there was significant difference between these two groups (p=0.02). The incidence rate of chromosomal trisomy was 59% (23/37) in ACA negative, 62% (8/13) in ACA positive and there was no significance between two groups. CONCLUSIONS: The significantly low incidence of chromosomal abnormalities in conceptal products of patients with IgG-ACA comparing that of patients with IgM-ACA suggests that this isotype of antibody have influence on the genesis of spontaneous abortions in genetically normal pregnancy. In further studies, additional trials are mandatory for obtaining a definitive conclusions about relationship between pathologic changes of conceptal products and pathophysiologic effects of IgG-ACA.

Three cases of successful pregnancy outcome after intensive care in the patients with complete uterine septum, cervical duplication and longitudinal vaginal septum / 대한산부인과학회잡지

Three cases of successful pregnancy outcome after intensive care in the patients with rare mullerian anomaly of complete uterine septum, hypoplastic cervical duplication and longitudinal vaginal septum in infertility clinic are reported. These presented three cases are the reports of supporting the embryologic hypothesis of bidirectional mullerian development which fusion and resorption begins at the isthmus and proceeds simultaneously in both the cranial and caudal directions rather than the classical views of unidirectional(caudal to cranial) mullerian development. Thus, we present here three cases of rare mullerian anomaly and their pregnancy outcomes in an attempt to alert gynecologist to the possible occurrence of such a malformation. In 2 cases, successful pregnancy outcomes were achieved after abdominal or hysteroscopic uterine septotomy before pregnancy and in the last case, successful pregnancy outcome intensive obstetric care was achieved even under uncorrected uterine anomaly and complete removal of uterine septum resulted in uneventful postoperative courses at the same time of cesarean section.

The clinical efficacy of medical treatment and / or laparoscopic surgery for the improvement of pregnancy rate after IVF - ET in the infertile patients with endometriosis / 대한산부인과학회잡지

OBJECTIVE: The aim of study was to evaluate the efficacy of medical and/or laparoscopic surgical treatment for improvement of reproductive outcome of in vitro fertilization and embryo transfer (IVF-ET) in the patients with endometriosis. METHODS: 296 IVF-ET cycles except 18 cycles of cancelled embryo-transfer (unfertilization; 16 cycles, high risk of ovarian hyperstimulation syndrome; 2 cycles) in 191 infertile women with endometriosis from January 1, 1995 to December 31, 1998 were included in this study. All women's ages were < or = 35 and the factor for infetility was endometriosis only and day 3 follicle stumulating hormone (FSH) level of all the cycles was < or = 10 mIU/ml in this study. All the baseline study about infertility was done before initiating treatment of infertility. The stage of endometriosis was recorded during diagnostic laparoscopy by WHO critera. Medical treatment (GnRH agonist or danazole) or laparoscopic surgery was done independently or combinedly by the physician's decision according to the disease entity and symptoms. Short or long protocols were used for controlled ovarian hyperstimulation and 3 day embryos were transferred (maximally 4 embryos) by standard procedures in our institute. We classified the cases as 4 groups : group 1 (without pre-treatment, 80 cycles), goup 2 (laparoscopic surgery only, 37 cycles), group 3 (medication only, 140 cycles), group IV (combined pre-treatment, 39 cycles). RESULTS: The mean age (years old, mean +/- SEM) was 31.5 +/- 0.3 (group 1), 31.6 +/- 0.5 (group 2), 31.5 +/- 0.2 (group 3), 31.7 +/- 0.4 (group 4) respectively. The duration of infertility (months) was 57.7 +/- 3.3, 64.5 +/- 4.8, 59.1 +/- 1.9, 52.0 +/- 3.7 respectively among groups. The viable pregnancy rate (over 28 gestational weeks, VPR) was 12.5 % (10/80) in goup 1, 13.5 % (5/37) in goup 2, 14.3 % (20/140) in group 3, 30.8 % (12/39) in group 4 and there was statistically significant difference between group 1 and group 4 (P=0.03, Chi square test). The total used gonadotropins (ampules) for controlled ovarian hyperstimulation were 28.2 +/- 0.6.

Adhesion and invasion of shed endometrium in an in-vitro model for endometriosis using amnion / 대한산부인과학회잡지

No abstract available.

Anti-TNF-alpha Therapy for Rheumatoid Arthritis / 대한류마티스학회지

No abstract available.

A Case of Polyarteritis Nodosa Successfully Treated with Deflazacort / 대한류마티스학회지

Polyarteritis nodosa(PAN), a systemic vasculitis involving multiple organs including the nervous system, requires a long-term glucocorticoid therapy. Deflazacort is a synthetic glucocorticoid, which has been claimed to have less side effects, but its use for vasculitis has never been reported in the literature. We report a case of polyarteritis nodosa presenting with mononeuritis multiplex causing a left foot drop, which was successfully treated with deflazacort.

Non-systemic Vasculitic Neuropathy Presenting as Ascending Paralysis

Typical vasculitic neuropathy commonly manifests as a subacute multiple mononeuropathy, symmetrical or asymmetrical sensori-motor polyneuropathy. Various clinical presentations of peripheral neuropathy may confuse the diagnostic approach sometimes. A 76-year old man presented progressive areflexic ascending paralysis. gait ataxia, severe vibration and position sense impairment for 1 month. We initially considered as subacute demyelinating polyneuropathy. Electrophysiologic studies showed mainly axonopathy with some evidence of demyelination. We performed sural nerve biopsy and diagnosed as vasculitic neuropathy. No laboratory data or clinical findings favored systemic vasculitic involvement. So we concluded vasculitis confined to the peripheral nerves. Vasculitic neuropathy rarely presented as large myelinated nerve fiber disease. It should be considered the clinical variability of vasculitic neuropathy so extensive studies are needed in the case of peripheral polyneuropathy with indefinite cause.

Reproductive Outcome of Women with Recurrent Abortions or Infertility Following Treatment by Operative Hysteroscopy for an Intrauterine Septum / 대한산부인과학회잡지

Uterine anomalies have been reported in 4% of women with infertility and in up to 15% of those with recurrent abortion. One of the major intrauterine disorder associated with infertility and recurrent abortions is intrauterine septum, The reproductive outcome of 41 patients of intrauterine septum (7 complete, 34 incomplete) with repeated abortions or infertility was assessed after the uterine septotomy. 5 of 7 patients with comlete uterine septum undergone uterine septotomy (3; hysteroscopic metroplasty, 2; abdominal metroplasty) had total 6 pregnancies and all of them had live biths. 28 patients with incomplete uterine septum got the hysteroscopic intrauterine septotomy and the viable pregnancy rate was 62% (3 ongoing pregnancies, 13 live biths of total 26 pregnancies). 6 patients with incomplete uterine septum had not the operation and 5 patients had 5 live births after total 6 pregnancies with 1 spontaneus abortion. Even though, the number of cases were small, the live birth rate in the group of septotomy of the patients of complete uterine septum (100%, 6/6) was higher than that in the group of not-done (50%, 1/2). The live birth rate in the group of not-done of the patients with incomplete uterine septum (83%, 5/6) was higher than that in the group of hysteroscopic uterine septotomy (62%, 16/26), but 5 of 6 had short uterine septal length (<1 cm), 1 had 1.5 cm septal length in the group of not-done. All the patients with successful pregnancy outcome had no other co-factors at the diagnostic laparoscopy, but the 5 primary infertility patients with no live birth even after treatment (all were with incomplete septum; 3 undergone hysteroscopic septotomy, 2 not-done with one abortion) had other co-factors such as endometriosis, peritoneal or tubal facor. In conclusion, hysteroscopic uterine septotomy would be useful for the patients with habitutal abortion or infertility and more advanced managemnet protocols should be applied to the patients having other co-factors if there was no pregnancy even after the uterine septotomy.

Comparative Study of Perinatal Outcome and the Incidene of Congenital Anomalies of Babies Born after Intracytoplasmic Sperm Injection (ICSI) and Conventional In-vitro Fertilization (IVF) / 대한불임학회지

The safety of ICSl as a novel procedure of assisted fertilization may be assessed by the health of the baby born. In order to evaluate the safety of ICSI, perinatal outcome and congenital anomaly of the babies born after ICSI were compared with those of babies born after IVF (control group). We analysed the clinical data from the obstetric and pediatric records, including the information obtained through telephone. The results are as follows; Mean gestaional age (+/-SEM) and birth weight in singleton pregnancy were 38.8+/-1.9 weeks and 3209.7+/-501.9gm in IVF group, 39.0+/-2.2 weeks and 3289.9+/-479.5gm in ICSI group, respectively. Mean gestational age and birth weight in twins were 36.8+/-2.1 weeks and 2512.8+/-468.0gm in IVF group, 36.5+/-2.8 weeks and 2492.7+/-537.1gm in ICSI group. In IVF group, perinatal mortality rates were 8.5 in singletons and 56.6 in twinst for the ICSI singletons and ICSI twins, the perinatal mortality rates were 11.6 and 49.0, respectively. The incidence of congenital malformations was 3.6% (8/224) in IVF group and 2.1% (4/188) in ICSI group, there was no statistical difference (p>0.05, Fisher's exact test). The incidence of major congenital anomalies was 0.9% (2/224; pulmonary artery hypoplasia, renal cystic dysplasia) in IVF group and 1.1% (2/188; holoprosencephaly, Cri du chat syndrome) in ICSI groups (p>0.05, Fisher's exact test). Similarly, there was no significant difference in incidence of minor congenital anormalies 2.7% (6/224) in IVF group and 1.1% (2/188) in ICSI group respectively (p>0.05, Fisher's exact test). In conclusion, there was no difference in the perinatal outcome and the incidence of congenital anomalies between the babies born after ICSI and those after conventional IVF.

alphabeta T - Helper Cell Dependency in the Development of Anticardiolipin and Anti - beta2 Glycoprotein I Antibodies in MRL / MP - lpr / lpr Mice / 대한면역학회지

No abstract available.

Clinical study on lymphocyte immunization in recurrent abortion / 대한산부인과학회잡지

No abstract available.