Comparison of karyotypes in first trimester spontaneous fetal losses in relation to successful or failure to transvaginal ultrasonographic detection of fetal heart activity / 대한산부인과학회잡지

OBJECTIVE: Genetic defects of the zygote, such as chromosome aberration, are the most frequent cause of abnormal embryonic development and spontaneous abortion. Recent advances in ultrasonographic technology have allowed documentation of early embryonic growth and development and some studies have suggested that once fetal cardiac activity has been demonstrated at 8-10 weeks of gestation, the subsequent spontaneous abortion rate is reported to be less than 5% of pregnancies. Some authors suggested that, abortions in which fetal cardiac activity was once demonstrated, chromosomal anomalies are considered to play important roles in these abortions. But, other studies failed to reveal any relationship between occurrence of chromosomal abnormalities and ultrasonographic detection of fetal heart activity. The aim of the study was to determine the relationship of ultrasonographic detection of fetal heart activity and the abnormal karyotypes in spontaneous abortions. DESIGN: A 1-year retrospective, study. MATERIALS AND METHODS: 158 pregnancies (129 spontaneous, 29 assisted ovulatory cycles) that aborted in the first trimester between January 1,2001 and December 31, 2001, in Samsung Cheil Hospital had chromosomal analysis performed on the products of conception and had ultrasonographic examination prior to spontaneous abortion. Of these pregnancies 62 were detection of transvaginal ultrasonographic detection of fetal heart activity prior to abortion and 96 were failure to detect fetal heart activity. Fetal tissue was removed by dilatation and curettage. Cytogenetic studies were performed from cultures of dissected chorionic villi and G-sac. And then, we compared the incidence and the characteristics of abnormal karyotypes between fetal heart activity detected group (Group I) and failure to detect fetal heart activity group (Group II) prior to abortion. RESULTS: Of 158 spontaneous abortions who carrying chromosomal analysis, 98 had abnormal karyotypes. (60 trisomies, 11 polyploides, 10 mosaicism, 5 monosomies and 12 structural abnormalities). The overall incidence of chromosomal aberrations in our study group was 62.0% (98/158). Chromosomal aberrations were found in 59.7% (37/62) of abortuses in group I and 63.5% (61/96) in group II and it was insignificant statistically. The frequency of type of abnormal karyotype in both groups (Group I: 25 (40.3%) trisomies, 1 (1.6%) polyploides, 0 (0%) mosaicism, 8 (12.9%) and 3 (4.8%) monosomies, Group II: 35 (36.5%) trisomies, 10 (10.4%) polyploides, 5 (5.2%) mosaicism, 2 (2.1%) monosomies and 9 (9.4%) structural abnormalities) were insignificant statistically. When we stratified both groups and analyzed the abnormal karyotype by maternal age, those were not statistically different in both groups. CONCLUSION: In our study, chromosomal abnormalities in spontaneous abortion did not differ according to ultrasonographic detection of fetal heart activity, and the type of abnormal karyotype were not distributed differently.

The Efficacy of Recombinant Human Follicle Stimulating Hormone (rhFSH) in Human IVF-ET Program / 대한불임학회지

OBJECTIVES: Recently, recombinant FSH (rFSH) has been manufactured using a Chinese hamster ovary cell line transfected with the gene encoding human FSH. Both rFSH and urinary gonadotropin (uFSH) could be used for controlled ovarian hyperstimulation (COH). However, uFSH implies a number of disadvantages, such as batch-to-batch inconsistency, no absolute source control, dependence on large amounts of urine, low specific activity, and low purity. The purpose of this study was to evaluate the efficacy of rFSH in human IVF-ET program. MATERIALS AND METHODS: A total of 508 infertile women was enrolled in this study. They are classified into rFSH group (n=177) or uFSH group (n=331), and all of them were matched by age and cause of infertility in same period. The Puregon(R) (Organon, Holland) was used as rFSH, and the Metrodin-HP(R) (Serono, Switzeland) and Humegon(R) (Organon, Holland) was used as uFSH. We subdivided the patients into three age groups. The outcomes of IVF-ET program were analyzed using the statistical package for social sciences (SPSS). RESULTS: There was no significant differences in the level of estradiol on hCG injection day, the numbers of retrieved oocytes, matured oocytes, fertilized oocytes, transferred embryos, frozen embryos between the two groups. The total dose (IU) of gonadotropin for COH was significantly lower in the rFSH group compared to uFSH group (1339+/-5491.1 vs 2527.8+/-1075.2 IU, p<0.001). Clinical pregnancy rate per embryo transfer in the rFSH group showed increasing tendency, compared to the uFSH group, but there was no statistical significance (35.2% vs 29.3%). Our results demonstrated that the relative efficiency of rFSH compared with uFSH is higher in older patients. CONCLUSIONS: The ovarian stimulatory effect and clinical outcome of recombinant FSH was similar to that of the urinary gonadotropin. The IVF-ET cycles with significantly lower dose of gonadotropin in rFSH group showed comparable results. Therefore, we suggest that recombinant FSH is more potent and effective than urinary gonadotropin.

Obstetric outcome in women with a history of recurrent miscarriage / 대한산부인과학회잡지

OBJECTIVE: To obtain etiology and obstetric outcome of women who had a history of recurrent miscarriage. METHODS: From 1 June 1998 to 30 June 2000, 82 patients who attended infertility & current miscarriage clinic at Samsungcheil hospital and progressed beyond 24 weeks gestation following pregnancy were included in this study. The control population was 154 pregnancies considering age and parity over the same period. Retrospectively, we analyse the etiology of recurrent miscarriage and compare obstetric outcomes of two groups. RESULTS: The etiology of recurrent miscarriage was immunologic factor (36.6%), unexplained (30.4%), anatomic cause (13.4%), endocrinologic abnormality (13.4%) and chromosomal abnormality (5.6%). The rate of preterm delivery (11%) and incidence of pregnancy induced hypertention (8.5%) were significantly higher than those of control group (3.2% and 2.5% respectively). There was no significant difference in the rate of small for gestational age, oligohydroamnios, cesarean section, perinatal loss and the incidence of gestational diabetes mellitus. CONCLUSION: The pregnancy with a history of recurrent miscarriage is associated with increased risk of pregnancy induced hypertension and preterm delivery and represent a population at high risk of obstetric problems. Therefore, close surveillance during antenatal period is required.

Outcome of Preimplantation Genetic Diagnosis for Chromosome Aneuploidy and Genetic Disease / 대한불임학회지

OBJECTIVES: Chromosome aneuploidy is associated with recurrent abortion and congenital anomaly and genetic diseases occur repeatedly in the specific families. Preimplantation genetic diagnosis (PGD) can prevent aneuploidy or genetic disease by selecting normal embryos before implantation and is an alternative to prenatal diagnosis. The aim of this study is to assess the outcome of PGD cycles by using FISH or PCR, and to determine the clinical usefulness and values in patients with risk of chromosomal aneuploidy or genetic disease. MATERIALS AND METHODS: From 1995 to Apr. 2001, a total of 108 PGD cycles in 65 patients with poor reproductive outcome were analyzed. The indications of PGD were translocation (n=49), inversion (n=2), aneuploidy screening (n=7), Duchenne muscular dystrophy (n=5) and spinal muscular atrophy (n=2). PGD was applied due to the history of recurrent abortion, previous birth of affected child or risk of aneuploidy related to sex chromosome aneuploidy or old age. Blastomere biopsy was performed in 6~10 cell stage embryo after IVF with ICSI. In the single blastomere, chromosome aneuploidy was diagnosed by using FISH and PCR was performed for the diagnosis of exon deletion in DMD or SMA. RESULTS: The FISH or PCR amplification was successful in 94.3% of biopsied blastomeres. The rate of transferable balanced embryos was 24.0% in the chromosome translocation and inversion, 57.1% for the DMD and SMA, and 28.8% for the aneuploidy screening. Overall hCG positive rate per transfer was 17.8% (18/101) and clinical pregnancy rate was 13.9% (14/101) (11 term pregnancy, 3 abortion, and 4 biochemical pregnancy). The clinical pregnancy rate of translocation and inversion was 12.9% (11/85) and abortion rate was 27.3% (3/11). In the DMD and SMA, the clinical pregnancy rate was 33.3% (3/9) and all delivered at term. The PGD results were confirmed by amniocentesis and were correct. When the embryos developed to compaction or morula, the pregnancy rate was higher (32%) than that of the cases without compaction (7.2%, p<0.01). CONCLUSIONS: PGD by using FISH or PCR is useful to get normal pregnancy by reducing spontaneous abortion associated with chromosome aneuploidy in the patients with structural chromosome aberration or risk of aneuploidy and can prevent genetic disease prior to implantation.

Outcome of Preimplantation Genetic Diagnosis for Chromosome Aneuploidy and Genetic Disease / 대한불임학회지

OBJECTIVES: Chromosome aneuploidy is associated with recurrent abortion and congenital anomaly and genetic diseases occur repeatedly in the specific families. Preimplantation genetic diagnosis (PGD) can prevent aneuploidy or genetic disease by selecting normal embryos before implantation and is an alternative to prenatal diagnosis. The aim of this study is to assess the outcome of PGD cycles by using FISH or PCR, and to determine the clinical usefulness and values in patients with risk of chromosomal aneuploidy or genetic disease. MATERIALS AND METHODS: From 1995 to Apr. 2001, a total of 108 PGD cycles in 65 patients with poor reproductive outcome were analyzed. The indications of PGD were translocation (n=49), inversion (n=2), aneuploidy screening (n=7), Duchenne muscular dystrophy (n=5) and spinal muscular atrophy (n=2). PGD was applied due to the history of recurrent abortion, previous birth of affected child or risk of aneuploidy related to sex chromosome aneuploidy or old age. Blastomere biopsy was performed in 6~10 cell stage embryo after IVF with ICSI. In the single blastomere, chromosome aneuploidy was diagnosed by using FISH and PCR was performed for the diagnosis of exon deletion in DMD or SMA. RESULTS: The FISH or PCR amplification was successful in 94.3% of biopsied blastomeres. The rate of transferable balanced embryos was 24.0% in the chromosome translocation and inversion, 57.1% for the DMD and SMA, and 28.8% for the aneuploidy screening. Overall hCG positive rate per transfer was 17.8% (18/101) and clinical pregnancy rate was 13.9% (14/101) (11 term pregnancy, 3 abortion, and 4 biochemical pregnancy). The clinical pregnancy rate of translocation and inversion was 12.9% (11/85) and abortion rate was 27.3% (3/11). In the DMD and SMA, the clinical pregnancy rate was 33.3% (3/9) and all delivered at term. The PGD results were confirmed by amniocentesis and were correct. When the embryos developed to compaction or morula, the pregnancy rate was higher (32%) than that of the cases without compaction (7.2%, p<0.01). CONCLUSIONS: PGD by using FISH or PCR is useful to get normal pregnancy by reducing spontaneous abortion associated with chromosome aneuploidy in the patients with structural chromosome aberration or risk of aneuploidy and can prevent genetic disease prior to implantation.

Chromosomal Abnormality of Spontaneous Abortus in Relation to Transvaginal Ultrasonographic Finding / 대한산부인과학회잡지

OBJECTIVE: To determine the clinical value of human papillomavirus deoxyribonucleic acid(HPV DNA) testing by polymerase chain reaction(PCR), specifically to examine whether HPV testing could identify the women with Pap smears read as mostly atypical squamous cells of undetermined significance(ASCUS) or more. METHODS: HPV DNA testing by PCR for 3 high-risk cancer associated genotypes(HPV 16, 18, 33), repeat Pap smears and colposcopically directed punch biopsies were performed concurrently on 169 women referred for cervical cancer screening test with a previous Pap smear read as ASCUS or more. RESULTS: HPV DNA testing positivity was significantly associated with abnormal cytology and high-grade squamous intraepithelial lesion(HSIL) and squamous cell carcinoma(SCC) in histology(P=0.034). The sensitivity, specificity, positive predictive value(PPV), negative predictive value(NPV) of Pap smear and HPV testing for identifying 38 cases of histologically confirmed HSIL and carcinoma by different triage protocols(HPV positive or HSIL or SCC) among 169 women were 65.8%(25/38), 85.5%(112/131), 56.8%(25/44) and 89.6%(112/125), respectively. Also sensitivity, specificity, PPV and NPV were varied by ages and more higher in older. CONCLUSION: HPV DNA testing by PCR appears to offer an effective means by which women whose cervical Pap smears have been read as ASCUS or more could be triaged for colposcopically directed biopsy. The sensitivity for HSIL could be maintained in high and specificity markedly improved by HPV genotypes 16, 18, 33.

Clinical Significance of Serum Leptin Level in Adolescent Patients with Menstrual Abnormalities / 대한산부인과학회잡지

OBJECTIVES: Leptin is known as an endocrinologic mediator which acts on the hypothalamic- pituitary-ovarian axis. This study was undertaken to evaluate whether the serum leptin level affects the menstrual cycles of adolescents and to analyze the clinical features of adolescents with abnormal serum leptin levels. METHODS: Seventeen normal controls and 118 patients with menstrual abnormalities were included in this study. The ages of patients ranged from 15 to 25 years. Patients with menstrual abnormality were divided into five subgroups according to the etiologies: group I; premature ovarian failure(n=8), group II; primary amenorrhea without congenital structural abnormality(n=14), group III; oligomenorrhea(n=12), group IV; secondary amenorrhea(n=53), group V; dysfunctional uterine bleeding(n=31). After collection of blood samples, the serum leptin levels were measured with a radioimmunoassay kit. The serum leptin level and the corrected leptin level(leptin/body mass index(BMI)) were compared and the clinical features of those with abnormal leptin concentration (>mean+standard deviation,

Values of Alpha-fetoprotein of Maternal Serum in Normal Pregnancy / 영남의대학술지

Alphafetoprotein(AFP) is a glycoprotein synthesized by the fetus early in gestation by the yolk sac and later by the gastrointestinal tract and liver. The concentration of AFP is highest in fetal serum and amniotic fluid around 13th week, and 32nd week in maternal serum. Some conditions are associated with abnormal maternal serum AFP concentration. For examples, neural tube defects, omphalocele, renal anomalies are associated with elevated maternal serum AFP and fetal death, chromosomal trisomies are associated with low level of maternal serum AFP. So maternal serum AFP screening plays a significant role in assessing candidates for prenatal diagnosis and prenatal counselling in pregnant women. This study evaluates the normal ranges of AFP using enzyme immunoassay in normal pregnant women. We studied 500 normal pregnant women who visited the Department of Obstetrics & Gynecology, Yeungnam Medical Center, Yeungnam University during the period through January, 1993 to September, 1996. The group of the study were selected randomly at various gestational ages from 8 to 41 weeks. The results were summarized as follows: 1. The lowest level of AFP in our study group was 2.1ng/ml at 8 weeks of gestation. Thereafter serum alpha-fetoprotein concentrations rose rapidly to reach a peak value at 32nd week. 2. The mean levels of AFP in the primipara and multipara were 166.37+/-12.06ng/ml, and 223.78+/-14.00ng/ml, respectively, showing stastiscally significant difference between these two groups(p0.05). 4. The normal ranges of maternal serum AFP according to each gestational week were evaulated.

Two Cases of Combined Pregnancy Following IVF-ET / 영남의대학술지

Combined intrauterine and ectopic (heterotopic) pregnancy occurs in approximately 1 in 30,000 spontaneous gestations. Heterotopic gestations are increased in women who have had reconstructive pelvic surgery, Pelvic inflammatory disease and artificial ovarian hyperstimulation. Patients who require assisted reproductive technologies, such as in vitro fertilization / embryo transfer and gamete intrafallopian transfer, also have an increased risk of a heterotopic pregnancy. We experienced two cases of combined pregnancy following IVF-ET. Following is a report of these cases with a brief review of references.