Successful in Vitro Fertilization and Embryo Transfer after Transplantation of Cryopreserved Ovarian Tissue: Report of the First Korean Case

For patients at risk of premature ovarian failure with cancer treatment, it is an important option to re-implant the ovarian tissue (OT) after cryopreservation to preserve endocrine function and fertility. With this technique, about 30% of pregnancy success rate and about 90 live births have been reported to date. However, there has been no case report of successful in vitro fertilization (IVF) and embryo transfer (ET) with oocytes collected from transplanted cryopreserved OT in Korea. We report a 30-year old woman with rectal cancer who underwent IVF and ET after cryopreserved OT thawing and re-implantation. She has been diagnosed with stage IIIC rectal cancer after surgery, and right ovary was removed and cryopreserved between cycles of chemotherapy. After completion of chemotherapy and radiotherapy, the patient underwent orthotopic transplantation of cryopreserved OTs. Three months after transplantation, the serum follicle-stimulating hormone level decreased from 91.11 mIU/mL to 43.69 mIU/mL. Thereafter, the patient underwent 11 ovarian stimulation cycles, and in 7 cycles, follicle growth was observed at the OT graft site. In one of these cycles, the oocyte was successfully retrieved and one embryo was transplanted after IVF. The patient was not pregnant, but the cryopreservation of OT can save the fertility after anticancer chemotherapy.

Methylenetetrahydrofolate Reductase Polymorphisms and Risk of Recurrent Pregnancy Loss: a Case-Control Study

The balance between coagulation and fibrinolysis is an essential part in early pregnancy. Mutations in methylenetetrahydrofolate reductase (MTHFR) gene lead to decreased activity of the enzyme and hyperhomocysteinemia, which then induces platelet aggregation by promoting endothelial oxidative damage, possibly resulting in adverse effect on maintenance of pregnancy. We investigated the role of MTHFR single nucleotide polymorphisms (SNPs), C677T and A1298C, in Korean patients with recurrent pregnancy loss (RPL). We conducted a prospective case-control study in the Korean population. Subjects included 302 women with 2 or more consecutive, unexplained, spontaneous miscarriages before 20 weeks of gestation and 315 control women without a history of recurrent miscarriages. The genotyping for C677T and A1298C polymorphisms was performed using the TaqMan assay. Continuous variables were compared using Student's t-test, and χ² test was used to evaluate differences in the genotype distributions between the RPL and the controls. The genotype distribution of both polymorphisms in the RPL group did not differ from those of the controls. For further analysis, if RPL patients were divided according to the numbers of pregnancy losses (≥ 2 and ≥ 3) neither group was significantly different compared with controls. MTHFR gene C677T and A1298C polymorphisms are not associated with idiopathic RPL in Korean women, suggesting that those may not be susceptible allelic variants or be deficient to cause RPL.

GnRH Agonist Stimulation Test (GAST) for Prediction of Ovarian Response in Controlled Ovarian Stimulation (COH) / 대한불임학회지

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 (E2) on cycle day two, 0.5 ml (0.525 mg) GnRH agonist (Suprefact, Hoechst) was injected subcutaneously. Serum E2 was measured 24 hours later. Initial E2 difference (deltaE2) was defined as the change in E2 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 deltaE2; group A (n=30):deltaE2<40 pg/ml, group B (n=52): 40 pg/ml< or =deltaE2<100 pg/ml, group C (n=20): deltaE2< or =100 pg/ml. COH was done by GnRH agonist/HMG/hCG and IVF-EF was followed. Ratio of E2 on day of hCG injection over the number of ampules of gonadotropins used (E2hCGday/Amp) was regarded as ovarian responsiveness. Poor ovarian response and overstimulation were defined as E2 hCGday less than 600 pg/ml and greater than 5000 pg/ml, respectively. RESULTS: Mean age (+/-SEM) in group A, B and C were 33.7+/-0.8*, 31.5 +/-0.6 and 30.6+/-0.5*, respectively (*: p<0.05). Mean basal FSH level of group A (11.1+/-1.1 mIU/ml) was significantly higher than those of B (7.4+/- 0.2 mIU/ml) and C (6.8+/-0.4 mIU/ml) 0<0.001). Mean E2hCGday of group A was significantly lower than those of group B or C, i.e., 1402.1+/-187.7 pg/ml, 3153.2+/- 240.0 pg/ml, 4078.8+/-306.4 pg/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+/-2.3, 24.2+/-1.1 and 18.5+/-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+/-1.1, 15.5+/-1.1 and 18.6+/-1.6, respectively (p<0.0001). By stepwise multiple regression, only deltaE2 showed a significant correlation (r=0.68, p<0.0001) with E2HCGday/Amp, while age or basal FSH level were not significant. Likewise, only deltaE2 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 E2 difference after GAST may be a better prognostic indicator of ovarian response to COH than age or basal FSH level. Since initial E2 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 Efficacy of Intravenous Immunoglobulin for the Prevention of Recurrent Spontaneous Abortion / 대한산부인과학회잡지

The aim of this study was to evaluate the efficacy of intravenous immunoglobulin treatment for recurrent spontaneous abortion. Immunologic causes in either alloimmune or autoimmune type have been suggested for more than 80% of these patients. Various immunotherapy including paternal leukocyte transfusion has been used, but there is controversy on its efficacy and side-effects. The proposed immunomodulatory mechanism of intravenous immunoglobulin includes passive transfer of blocking or anti-idiotype antibody, blockade of Fc receptors, enhancement of supressor T-cell function, down regulation of B cell function. In this study, we used intravenous immunoglobulin for the prevention of spontaneous abortion. Five patients with a history of two or more spontaneous abortions were enrolled in this study. Other etiologic factors such as anatomical, chromosomal, hormonal factors were excluded. Three of them were positive for anti-cardiolipin antibody (ACA). When the pregnancy was diagnosed at about five weeks of gestation, 30 g intravenous immunoglobulin was administered and continued up to 28 weeks with three weeks. Ongoing pregnancy beyond 20 weeks was considered successful. Four among five patients (80%) was successful in maintaining pregnancy now ongoing 20, 31, 33, 39 weeks. One patient with ACA positive had abartion due to anembryonic pregnancy. No adverse reaction was observed during the treatment. From these preliminary data, it is suggested that intravenous immunoglobulin treatment may be effective in maintaining pregnancy in patients with unexplained recurrent spontaneous abortion, Further studies are needed to clarify the its immunomodulatory mechanism and establish a more simplified protocol limiting the use at certain critical period of time.

Prediction and Clinical Evaluation of Hyperstimulation Syndrome / 대한산부인과학회잡지

OBJECTIVE: Ovarian hyperstimulation syndrome (OHSS) is one of the well known complication of conttolled ovarian hyperstimulation. Though there have been numerous protocols for the prevention of OHSS, it has not been completely preventable until now. This study was performed to identify clinical predictors for early and late OHSS. METHODS: A retrospective analysis of all IVF cycles in 1993 up to June 1996 was performed. OHSS was diagnosed using the criteria of Rabau modified by Schenker. All cases of OHSS reported in this study presented with marked ovarian enlargement, ascites, oliguria, hemoconcentration and electrolyte disturbance. Ovarian stimulation was carried out using a combination of gonadotrophin releasing hormone-agonist, follicle-stimulation hormone and human menopausal gonadotrophin. 27 patients has moderate or severe OHSS presenting 3-7 days post-human chorionic gonadotrophin (hCG), and 21 patients had severe OHSS presenting 12-17 days post-hCG. RESULTS: No patient with early OHSS went onto develop late OHSS, and no patient with late OHSS had demonstrated early OHSS. Logistic regression showed that early OHSS was predicted by the number of oocytes retrieved and the estradiol concentration on the day hCG injection (P<0.05). Late OHSS was predicted by the transferred embryos, B-hCG on 14 day after hCG injection (P<0.05). CONCLUSION: Early OHSS was an acute effect of the hCG administered prior to egg retrieval in women with high estradiol and large number of retrieved oocytes. Our analysis of the risk factors for early OHSS indicates that cryopreservation of all embryos will not alter the risk of early OHSS even though it should prevent late OHSS. Late OHSS was induced by the rising serum concentration of hCG produced by the early pregnancy, the number of transferred embryos must be adjusted carefully, since it was associated with multiple gestation.

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.

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.

The Affects of the Initial Fetal Number on Pregnancy Outcomes before Multifetal Pregnancy Reduction / 대한산부인과학회잡지

Multifetal pregnancy reduction(MFPR) appears to be an efficacious method for impro-ving the perinatal outcome of high order multifetal pregnancies(three or more fetuses). But it is controversial that larger initial fetal number before MFPR affects pregnancy outcomes adversely. The purpose of this study is to determine the affects of the initial fetal numbers on pregnancy outcomes and to compare the obstetrical outcomes according to the initial fe-tal numbers. Eighty four patients who conceived triplet or more by assisted reproductive technology(ART) in our infertility clinics and underwent MFPR to twins between January 1993 and December 1995. Sixteen patients were lost follow-up. Among the remaining 68 patients, four pateints were excluded from this study because of the pregnancy loss before 20 weeks gestation. The patients(n=64) were divided into three groups by the initial fetal number before reduction. 33 patients with triplet gestations(group 1), 18 patients with qua-druplets gestations(group 2), and 13 patients with quintuplet or more gestations(group 3) were retrospectively enrolled. Gestational age at delivery and birthweights were compared according to the initial fetal numbers. The mean maternal age was similar in each three groups. The results were as follows : 1) Although there was a trend of decreasing gestati-onal weeks at delivery and decreased birthweight in each groups(mean+/-SEM : 36.9+/-0.3, 34.7+/-1.3, 32.7+/-1.9 and 2,600+/-58, 2,161+/-215, 1,855+/-249 respectively), there were no stati-stical difference between group 1 and group 2, but there were significantly lower in group 3, compared with group1(p < 0.05). 2) The incidence of birth before 36 weeks gestation in each group 1, group 2, and group 3 were 12.1%, 38.9%, and 53.8% respectively(p < 0.05). 3) The incidence of low birthweight( < 2,500gm) in each group 1, group 2, and group 3 were 30.3%, 55.6%, and 69.2% respectively(p < 0.05). In conclusion, although MFPR reduced the high order multifetal pregnancy into twin pregnancy, the duration of gestation and the birth weight of newborn were still had a tendency of shortening and low respectively in high order multifetal pregnancy. Therefore strict control of the number of dominant follicles during superovulation and the number of transfered embryo in in vitro fertilization(IVF) is required for improving the pregnancy outcomes in ART.

Effect of Hydrosalpinx on IVF Outcome in Controlled Ovarian Hyperstimulation Cycles and CryopreservedEmbryo Transfer Cycles / 대한산부인과학회잡지

This study was performed to determine the effect of hydrosalpinx on the outcome with in vitro fertilization and embryo transfer(IVF-ET). Hydrosalpingeal fluid may leak into theuterine cavity during or after ovarian hyperstimulation and can cause deletorious effect onembryo or implantation. Herein, we reported the effect of hydrosalpinx on the cycle outcomeof IVF in controlled ovarian hyperstimulation cycles and cryopreserved-thawed embryotransfer cycles.In controlled ovarian hyperstimulation cycles, comparisons were made between 59 IVFcycles of 54 patients having tubal disease without hydrosalpinx(control group) and 36 IVFcycles of 35 patients carrying hydrosalpinx(hydrosalpinx group). Both clinical pregnancyand implantation rates were significantly lower in hydrosalpinx group(25.4 versus 8.3%,and 11.6 versus 2.0% respectively). Four ectopic pregnancies were noted in hydrosalpinxgroup compared to one in the control group.In cryopreserved-thawed embryo transfer cycles, comparisons were made between 27IVF cycles of 25 patients having tubal disease without hydrosalpinx(control group) and 13IVF cycles of 13 patients carrying hydrosalpinx(hydrosalpinx group). There was a tendencyof decreased pregnancy and implantation rates in hydrosalpinx group compared to the control(37.0 versus 15.4%, and 9.9% versus 4.0% respectively). One ectopic pregnancy was notedin the hydrosalpinx group compared to none in the control group.These data indicate that the presence of hydrosalpinx may negatively affect IVF outcome.We suggest that patients presenting with hydrosalpinx should consider surgical correctionto optimize their outcome with IVF procedure.

Results of Transfer of Cryopreserved Supernumerary Embryos Obtained after Conventional in vitro Fertilization and Intracytoplasmic Sperm Injection (ICSI) / 대한불임학회지

Intracytoplasmic sperm injection (ICSI) recently has been utilized widely as the most successful technique to overcome the unfertilization problem in cases of severe male infertility in couples who could not be treated by conventional IVF. Recently, indications of ICSI have been extended further and more fertilized oocytes become available. Thus, it is necessary to examine the efficiency of freezing the surplus embryos obtained from ICSI. We compared the survival rate and the future outcome of cryopreserved embryos obtained either after conventional IVF or ICSI during the same period. After ICSI or IVF, five best-quality embryos from each patient were transferred in the stimulation cycle and the surplus pronuclear (PN) stage oocytes or multicellular embryos were cryopreserved by slow freezing protocol with 1,2-propanediol (PROH) as a cryoprotectant.4 total of 792 embryos from ICSI trial were thawed and 65.2% (516/792) survived. The survival rates of PN stage oocyte, multicellular embryo and PN + multicellular embryo were 63.5%, 68.2%, 64.0%, respectively. After 111 transfers, 34 pregnancies were achieved, corresponding to a clinical pregnancy rate of 30.6% per transfers. We thawed 1033 embryos from IVF trials and 57.5% (594/1033) survived. In IVF cycle, the survival rates of PN stage oocyte, multicellular embryo and PN + multicellular embryo were 58.2%, 65.2%, 40.2%, respectively. Thirty eight clinical pregnancies were established after 134 transfers, corresponding to a pregnancy rate of 28.4% per transfer The cleavage rate of thawed PN stage oocytes from ICSI trial (61.3%) was significantly higher than those from conventional IVF (53.4%). The developmental rates of good embryo (> or = grade II) in thawed PN stage oocytes obtained from conventional IVF and ICSI were 63% and 65%, respectively. We concluded that PN stage oocytes, multicellular embryos resulting from ICSI procedure can be successfully frozen/thawed with reasonable clinical pregnancy rates comparable to those of IVF.

A Profound Impact of Patient Age on Pregnancy Outcome after Demonstration of a Live Fetus following IVF-ET / 대한산부인과학회잡지

In infertile patients, the pregnancy loss rate after demonstration of fetal heart beat ranges about 7 % to 11 %, which is relatively higher than that of normal population(about 1.5~3.3 %). But scanty data are available in evaluation of the influence of maternal age on pregnancy outcomes in IVF-ET patients. Thus, this study was done to assess the imp-act of maternal age on pregnancy loss rate after the early sonographic detection of fetal cardiac activity following IVF-ET. Pregnancy outcomes of 338 IVF-ET cycles from January 1, 1994 through December 31, 1995 were analyzed. Trans vaginal ultrasonography was done serially from the day 21 postconception and the presence of fetal heart activity was documented using a Samsung 125-MAX scanner with a 6.5-MHz transvaginal probe. Logistic regression analysis was done to determine the possible effects of various independent factors such as treatment pr- otocol, infertility factors, basal LH, FSH and E2, multifetal pregnancy reduction, and age of the wife, on probability of spontaneous pregnancy loss after confirmation of positive fetal heart beat. The overall pregnancy loss rate was 8.0 %(27/338). The probability of pregnancy loss after positive fetal heart beat increased with age of the wife(logistic regression analysis, P0.05). We conclude that spontaneous pregnancy loss rate after documentation of fetal cardiac activity increases as a function of the maternal age and a profound effect was observed after age 35. Thus, older patients should be counselled on the higher risk of spontaneous pregnancy loss.

Rapid fetal karyotyping by durect analysis of uncultured cytotropholbastic cells from second and third trimester placnetas:an accurate and rapid method / 대한산부인과학회잡지

No abstract available.

The ultrastructural changes of ovarian surface cell according to alterations in ovarian hormone / 대한산부인과학회잡지

No abstract available.