Síndrome de Cohen: reporte de caso y revisión de la literatura / Cohen syndrome: case report and literature review

Resumen Introducción: el Síndrome de Cohen es una enfermedad genética monogénica autosómica recesiva, que se origina a partir de mutaciones en el gen VPS13B (COH1). Se caracteriza por obesidad, retraso psicomotor, microcefalia, hipotonía, miopía progresiva, distrofia retiniana, neutropenia intermitente y rasgos faciales particulares. Objetivo: presentar el segundo caso reportado en Colombia, que fue confirmado mediante estudio molecular. También se presenta una breve revisión de la literatura médica más reciente sobre esta patología. Caso clínico: adolescente de 14 años con microcefalia, trastorno cognitivo, malformaciones menores asociadas, neutropenia y obesidad, con mutación homocigota del gen VPS13B. Conclusión: a pesar de ser un síndrome poco común, con importante variabilidad fenotípica, debe sospecharse con base en los criterios clínicos y en las patologías asociadas.

Abstract Introduction: cohen's syndrome is an autosomal recessive monogenic genetic disease, which originates from mutations in the VPS13B (COH1) gene. It is characterized by obesity, psychomotor retardation, microcephaly, hypotonia, progressive myopia, retinal dystrophy, intermittent neutropenia, and classic facial features. Objective: to present the second case reported in Colombia, which was confirmed by molecular study. A brief review of the most recent medical literature on this pathology is also presented. Clinical case: a 14-year-old adolescent with microcephaly, cognitive disorder, minor associated malformations, neutropenia, and obesity, with a homozygous VPS13B gene mutation. Conclusion: despite being a rare syndrome, with significant phenotypic variability, it should be suspected based on clinical criteria and associated pathologies.

A comparative study on the effects of intermittent drug withdrawal and small follicle aspiration on clinical outcomes in COH high-responders / 中国实用妇科与产科杂志

OBJECTIVE: To explore the treatment strategy for patients with hyperresponsiveness in the early and middle stages of superovulation induction(COH)by GnRH agonist down-regulation protocol in in vitro fertilization-embryo transfer(IVF-ET).METHODS: An analysis was made in 127 cases of IVF-ET performed in Reproductive Center of Shantou Central Hospital from June 2017 to June 2018.The patients were divided into 3 groups according to the different treatment:intermittent drug withdrawal group(group A),small follicle aspiration group(group B),and control group(group C).The embryo quality,pregnancy outcome,incidence of ovarian hyperstimulation syndrome(OHSS)and the number of cancelled fresh transplantation cycles were compared among the three groups.The embryo quality and pregnancy outcome was further compared between discontinuous withdrawal once(A1 group)and 2-3 times(A2 group),and between 1 day(A3 group)and 2-3 days(A4 group).RESULTS: The E2 level on HCG day,the rate of moderate and severe OHSS,cancellation rate and miscarriage rate in group A and group B were significantly lower than those in group C(P0.05).There was no significant difference in embryo quality or clinical outcomes between group A1 and A2,and between group A3 and A4(P>0.05).CONCLUSION: The intermittent withdrawal regimen is non-invasive,safe and simple,and can improve the quality of embryos.It is a suitable regimen for high-response patients to improve the chance of fresh transplantation.

The effect of COH and IVM on mitochondrial membrane potentials and cytoskeleton / 实用医学杂志

Objective To investigate the effect of different maturation methods on mitochondrial functions of oocytes and the possible mechanism. To explore novel ideas for developing assisted reproductive technology (ART). Methods Female mice were used as models and randomly allocated into three groups, COH, IVM and NC control. Oocytes maturated with different methods which were all simulated with those treatments in human IVF cycle. Immunofluorescence were used to measure the mitochondrial membrane potentials and analyze the cy-toskeleton. Results The mitochondrial membrane potential in the COH group was significantly lower than that in NC group and IVM group (P < 0.05). The proportion of normal cytoskeleton including spindle structure and chromosome configuration in the COH group and IVM group were significantly lower than that in the NC group (PCOH < 0.01, PIVM < 0.05). Conclusions Both COH and IVM can affect mitochondrial functions.

The predictive value of serum estradiol level during early phase of controlled ovarian hyperstimulation in IVF-ET / 实用医学杂志

Objective To evaluate the value of serum E2 levels during COH in predicting IVF-ET outcome. Method Data from 311 IVF-ET cycles received long protocol were collected and analyzed according to E 2 levels 5 days after stimulation:Group A (E2≤500 pmol/L), Group B (500 2 000 pmol/L). Results In groups with E2>1 000 pmol/L, the conditions of oocyte and embryo are higher than E2 2 000 pmol/L, the pregnancy rate become lowest. Conclusion E2 levels among 1 000~1 500 pmol/L during early COH predicts a better pregnancy outcome.

The effect of growth hormone in poor responders undergoing COH / 中国基层医药

Objective To observe the efficacy of growth hormone ( GH) co-treatment in poor responders undergoing IVF-ET.Methods To analyze all the ovaries low response patients treated by IVF/ICSI,80 cases were ran-domly divided into two groups:40 patients in GH group were given GH along with Gn daily until the HCG administra-tion.40 patients in the control group received the same treatment protocol except the GH co -treatment.The catching spawn number and MⅡova,fertile rate,the number of perfect embryos ,pregnant rate were observed .The serum con-centrations of IGF-I,IGFBP-3 were detected by ELISA and compared between the two groups .Results The number of oocytes retrieved ,number of MII oocytes ,cleavage ,number of embryos available of GH group were increased without statistical significance(all P>0.05 ).The serum IGFBP-3 level of 2 groups had no statistical significance .The fertile rate,pregnant rate ,serum IGF-I level were significantly higher in GH group than those in the control group ( all P<0.05).Conclusion GH co-treatment in poor responders could improve the outcome of IVF-ET,which imply that GH could improve the quality of oocytes and embryos related to the elevated IGF-1 level in serum .

Influence of multiple gene variation on IVF outcome / 中国药理学通报

Exogenous gonadotropins are widely used in controlled ovarian stimulation (COH) for patients undergoing in-vitro fertilization (IVF),because of the effect of follicle maturation and ovulation.Except for environmental factors such as age and ovarian reserve,genetic variability seems also to be a key factor in determining the ovarian response to the exogenous gonadotropins.In this review, the reason for the interindividual difference in ovarian resoponse as well as the influence of the genetic polymorphisms of FSHR and ESR on COH and IVF outcome has been summarized.

Efficacy of Frozen-Thawed ET in Patients with Old Age or Non-Pregnant in Fresh ET Cycles / 대한불임학회지

OBJECTIVE: The aim of this study was to evaluate the efficacy of frozen-thawed ET in poor prognosis patients such as the old age (38~44 years; OA group) and the patients who did not achieve clinical pregnancy with the first fresh ET cycle (non-pregnant patients; NP group). METHODS: Laboratory and clinical data were collected from fresh and frozen-thawed ET cycles of OA and NP group. Controlled ovarian hyperstimulation (COH) and conventional insemination or ICSI, in vitro culture and ET were performed by routine procedures. Supernumerary embryos were frozen by the slow freezing method, and frozen embryos were thawed by the rapid thawing method. Embryo development, pregnancy and implantation rates were statistically analyzed by Student t-test and chi square test. RESULTS: Mean ages were similar between fresh ET (40.0+/-1.8 years, n=206) and frozen-thawed ET (39.9+/-1.9 years, n=69) cycles in OA group. However, the clinical pregnancy and implantation rate of subsequent frozen-thawed ET significantly higher than those of fresh ET cycles (29.0% and 11.2% vs. 16.5% and 7.0%, p<0.05). In NP group, there was no difference in the mean age between fresh ET (31.2+/-2.3 years, n=40) and frozen-thawed ET (31.9+/-3.1 years, n=119) in subsequent cycles. The clinical pregnancy and implantation rates were similar between the subsequent fresh ET (42.5% and 22.6%) and the frozen-thawed ET (40.3% and 18.8%). CONCLUSION: In old age patients, higher pregnancy rate of frozen-thawed ET compared to fresh ET cycles in this study. It may be related that better uterine environments for implantation in frozen-thawed ET cycles than that of non-physiological hormonal condition in uterus of fresh COH cycles.

The Comparion of Pregnancy Outcomes between GnRH Agonist and GnRH Antagonist Cycles in Women with Advanced Age / 대한불임학회지

OBJECTIVE: To compare the clinical results and pregnancy outcomes of in vitro fertilization (IVF) between GnRH antagonist cycles and GnRH agonist (GnRH-a) cycles including flare-up and long protocol in women with advanced age. MATERIALS AND METHODS: Retrospective clinical study. From January 2001 to September 2003, IVF cycles of female patient 37 years over were included in this study. GnRH-a long protocol (62 cycles, 61 patients) and GnRH antagonist multi-dose flexible protocol (66 cycles, 51 patients) were compared with the control group of GnRH-a flare-up protocol (151 cycles, 138 patients). IVF cycles for non-obstructive azoospermia (NOA), endometriosis III, IV and polycystic ovarian syndrome (PCOS) were excluded in this study. Clinical results such as total gonadotropin dose, serum E2 on hCG administration, the number of retrieved oocytes and the pregnancy outcomes - clinical pregnancy rate (CPR), implantation rate (IR) and live birth rate (LBR) per embryo transfer - were compared. RESULTS: There were significant differences in the total dose of gonadotropin (GnRH-a flare-up vs. GnRH-a long vs. GnRH-antagonist; 41.8 vs. 54.7 vs. 24.8), serum E2 on hCG administration (1787.2 vs. 1881.6 vs. 788.0), the numbers of retrieved oocytes (8.1 vs. 11.1 vs. 4.5) and endometrial thickness (9.1 vs. 10.4 vs. 8.0) which were significantly lower in GnRH-antagonist cycles. But pregnancy outcomes shows no significant differenced in CPR (25.0% vs. 35.8% vs. 24.5%), IR (11.7% vs. 12.3% vs. 10.1%) and LBR (15.8% vs. 28.3% vs. 15.1%) CONCLUSION: In women with advanced age, GnRH-antagonist cycles can result in comparable pregnancy outcomes to GnRH-a cycles including flare-up and long protocol. GnRH-a long protocol show higher CPR, IR and LBR than GnRH antagonist multi-dose flexible protocol and flare-up protocol without significant differences.

Clinical efficacy of GnRH antagonist multiple dose protocol and GnRH agonist long protocol in controlled ovarian hyperstimulation using rFSH in IVF-ET patients / 대한산부인과학회지

OBJECTIVE: To compare the efficacy of GnRH antagonist multi dose protocol in controlled ovarian hyperstimulation (COH) for IVF-ET or ICSI with GnRH agonist long protocol. METHODS: From January 2003 to December 2004, total of 583 cycles which underwent IVF-ET or ICSI using r-FSH were enrolled in this study. 447 cycles of the study group were performed in controlled ovarian hyperstimulation by using GnRH antagonist multi dose protocol and 136 cycles of the control group were performed by using GnRH long protocol. We compared patients characteristics, controlled ovarian hyperstimulation outcomes and IVF-ET outcomes between two groups. RESULTS: Patients characteristics and baseline hormone levels were not different between the two groups. The duration of stimulation was significantly shorter in study group comparing with control group (12.8+/-1.5 days vs 13.7+/-1.7 days, p<0.05). There were no differences between the two groups in the number of follicles, endometrial thickness and serum E2 level on hCG day. The pregnancy rate seemed to be lower in the study group (32.4% vs 35.4%), but the difference was not statistically significant. There were also no differences in number of oocytes retrieved, matured oocytes, fertilized oocytes and transferred embryos between two groups. CONCLUSION: GnRH antagonist multi dose protocol in COH might be a simple and effective method compared with GnRH agonist long protocol.

Clinical Efficacy of Low-dose Aspirin and Prednisolone in Controlled Ovarian Hyperstimulation for In Vitro Fertilization and Embryo Transfer / 대한산부인과학회지

OBJECTIVE: To determine whether the use of low-dose aspirin and prednisolone in controlled ovarian hyperstimulation (COH) with GnRH agonist long protocol improves the outcomes of in vitro fertilization and embryo transfer (IVF-ET). METHODS: Two hundred and forty IVF-ET cycles were assigned to four groups: control group (aspirin(-) and prednisolone(-), n=59), low-dose aspirin group (aspirin(+) and prednisolone(-), n=43, Group 1), prednisolone group (aspirin(-) and prednisolone(+), n=80, Group 2), and low-dose aspirin and prednisolone group (aspirin(+) and prednisolone(+), n=58, Group 3). The COH and pregnancy outcomes were retrospectively compared among the four groups. RESULTS: Group 1 showed higher fertilization rate with a borderline significance compared to control group (73.6% vs. 64.1%, p=0.050). Serum estradiol (E2) level on hCG day was 995.5+/-767.5 pg/mL in control group, 1,550.7+/-1,254.5 pg/mL in group 1, 1,469.2+/-1,206.6 pg/mL in group 2 and 1,796.0+/-1,548.0 pg/mL in group 3 and higher in the three treatment groups compared to control (p=0.012, p=0.006, p<0.001, respectively). Embryo score per transferred embryo was also higher in Group 1 (17.4+/-8.4, p=0.001) and 3 (16.0+/-6.1, p<0.001) compared to control (12.2+/-5.1). There were no significant differences in the implantation and the pregnancy rates among the four groups. CONCLUSION: The use of low-dose aspirin or prednisolone may be beneficial in IVF-ET patients undergoing COH with GnRH agonist long protocol. Further larger-scale prospective randomized investigations are necessary to confirm these findings.

Correlation of vascular endothelial growth factor concentrations in follicular fluid with the ovarian response as well as the age in women undergoing controlled ovarian hyperstimulation / 대한산부인과학회지

OBJECTIVE: To elucidate the correlation of vascular endothelial growth factor (VEGF) concentrations in follicular fluid (FF) with the ovarian response as well as the age in women undergoing controlled ovarian hyperstimulation (COH). METHODS: This study was performed in 72cycles who underwent COH for in vitro fertilization at infertility clinic of Changwon Hanmaeum Hospital and Pusan National University Hospital from Aug., 2003 to Dec., 2003. Each FF was collected at the oocyte retrieval according to the follicular size and VEGF concentrations in FF were assessed. We analyzed the correlation of VEGF concentrations in FF with ovarian response as well as the age in women undergoing COH. RESULTS: In 72cycles, the clinical pregnancy rate was 37.5% (27cycles). There were no significant differences in patient's age, ampules of gonadotropin used, estradiol (E2) level on the day of hCG administration, the number of oocyte retrieved, and fertilization rate between pregnant and nonpregnant groups. However, positive correlation was found between the follicular size and VEGF concentrations in FF in pregnant and nonpregnant groups. No significant correlation was found between age and VEGF concentrations in FF. There were no significant differences in the VEGF concentrations in FF between pregnant and nonpregnant women by age. CONCLUSION: These results suggest that VEGF concentrations in FF cannot be the marker for the prediction of ovarian response, and have no correlation with all parameters of COH including patients' age with exception for the follicular size.

Correlation of Nitric Oxide Concentrations in Follicular Fluid with the Ovarian Response as well as the Age in Women Undergoing Controlled Ovarian Hyperstimulation / 대한산부인과학회지

OBJECTIVE: To elucidate the correlation of nitric oxide (NO) concentrations in follicular fluid (FF) with the ovarian response as well as the age in women undergoing controlled ovarian hyperstimulation (COH). METHODS: This study was performed in 72 cycles of whom underwent COH for in vitro fertilization at infertility clinic of Changwon Hanmaeum Hospital and Pusan National University Hospital from Aug., 2003 to Dec., 2003. Each FF was collected at the oocyte retrieval and NO concentrations in FF were assessed. We analyzed the correlation of NO concentrations in FF with the ovarian response as well as the age in women undergoing COH. RESULTS: Among 72 cycles, the clinical pregnancy rate was 37.5% (27cycles). There were no significant differences in patient's age, ampules of gonadotropins used, estradiol level on the day of hCG administration, the number of oocytes retrieved, and fertilization rate between pregnant and nonpregnant groups. However, negative correlation was found between the follicular size and NO concentrations in FF. No significant correlation was found between age and NO concentrations in FF. Comparing NO concentrations in FF between pregnant and nonpregnant women by age, NO concentrations in FF were higher at nonpregnant women, significantly those of them more than 40 years old. CONCLUSION: These results suggest that NO concentrations in FF cannot be a marker for the ovarian response, and have no correlation with all parameters of COH including patients' age with exception for the follicular size.

The Effect of Follicle-Stimulating Hormone Receptor (FSHR) Polymorphism on Outcomes of Controlled Ovarian Hyperstimulation (COH) and In-vitro Fertilization and Embryo Transfer (IVF-ET) / 대한불임학회지

OBJECTIVE: To investigate the association of FSH receptor (FSHR) polymorphism at position 680 with outcomes of controlled ovarian hyper-stimulation for IVF-ET in Korean women. Design: Genetic polymorphism analysis. MATERIALS AND METHODS: The FSHR polymorphism was analyzed by PCR-RFLP in 172 ovulatory women below the age of 40 year. Patients with polycystic ovary syndrome, endometriosis, or previous history of ovarian surgery were excluded. RESULTS: Genotype distribution was 41.9% for the Asn/Asn, 47.7% for the Asn/Ser, and 10.5% for the Ser/Ser FSHR genotype group. There was no difference in age of subjects and infertility diagnosis between genotype groups. When the patients were grouped according to their FSHR genotype, the basal levels of FSH (day 3) were significantly different among the three groups (6.0+/-0.3 IU/L (mean+/-SEM), 5.8+/-0.3 IU/L, and 8.6+/-1.2 IU/L for the Asn/Asn, Asn/Ser, and Ser/Ser groups, respectively, p=0.002). The Ser/Ser group showed a higher total doses of gonadotropins required to achieve ovulation induction, and a lower serum estradiol levels at the time of hCG administration compared with other two groups, but the differences were of no statistical significance. The numbers of oocytes retrieved were significantly different among the three groups (8.6+/-0.8, 9.9+/-0.6, and 6.3+/-0.9, for the Asn/Asn, Asn/Ser, and Ser/Ser groups, respectively, p=0.049). Clinical pregnancy rates were 42.4%, 25.9%, and 29.4% for the Asn/Asn, Asn/Ser, and Ser/Ser groups, respectively. CONCLUSION: Homozygous Ser/Ser genotype of FSHR polymorphism at position 680 was associated with decreased ovarian response to gonadotropin stimulation for IVF-ET.

Clinical Efficacy of Reduced Dose GnRH Agonist Long Protocol for Controlled Ovarian Hyperstimulation in IVF-ET Patients with High Basal Serum FSH Level / 대한산부인과학회잡지

OBJECTIVE: To evaluate the clinical efficacy of half-dose and further reduced dose GnRH agonist long protocols for controlled ovarian hyperstimulation (COH) in in vitro fertilization and embryo transfer (IVF-ET) patients with high basal serum FSH level. METHODS: One hundred and two IVF-ET cycles performed in 84 infertile patients with high basal serum FSH level (FSH>10.0 mIU/mL) were included in this retrospective study. Study subjects were assigned in two groups: continuous half-dose GnRH agonist long protocol (Group A, n=63) vs. further reduced dose GnRH agonist long protocol (Group B, n=39) from half-dose at the start of GnRH agonist to 1/3 or 1/4 dose after pituitary suppression. Exogenous FSH or hMG was administered for COH in step-down mode, 4 or less embryos were transferred, and intramuscular progesterone or 8% progesterone gel was used for the luteal support. RESULTS: Serum estradiol (E2) level on hCG day was significantly higher in Group B (1,318.3 +/- 1,120.4 vs. 2,054.9 +/- 1,773.5 pg/mL, p=0.015). The number of transferable embryos was also significantly higher in Group B (2.9 +/- 1.7 vs. 3.7 +/- 2.0, p=0.027). There was no statistically significant difference in the outcomes such as the dose of gonadotropins administered, the number of oocytes retrieved, and the clinical pregnancy rate. CONCLUSION: GnRH agonist long protocol with the reduced dose from half-dose at the start to 1/3 or 1/4 of dose after pituitary suppression may be more beneficial for COH in IVF-ET patients with high basal serum FSH level. Further prospective randomized controlled study in a larger scale will be necessary to confirm this findings.

Clinical Efficacy of Reduced Dose GnRH Agonist Long Protocol for Controlled Ovarian Hyperstimulation in IVF-ET Patients with High Basal Serum FSH Level / 대한산부인과학회잡지

OBJECTIVE: To evaluate the clinical efficacy of half-dose and further reduced dose GnRH agonist long protocols for controlled ovarian hyperstimulation (COH) in in vitro fertilization and embryo transfer (IVF-ET) patients with high basal serum FSH level. METHODS: One hundred and two IVF-ET cycles performed in 84 infertile patients with high basal serum FSH level (FSH>10.0 mIU/mL) were included in this retrospective study. Study subjects were assigned in two groups: continuous half-dose GnRH agonist long protocol (Group A, n=63) vs. further reduced dose GnRH agonist long protocol (Group B, n=39) from half-dose at the start of GnRH agonist to 1/3 or 1/4 dose after pituitary suppression. Exogenous FSH or hMG was administered for COH in step-down mode, 4 or less embryos were transferred, and intramuscular progesterone or 8% progesterone gel was used for the luteal support. RESULTS: Serum estradiol (E2) level on hCG day was significantly higher in Group B (1,318.3 +/- 1,120.4 vs. 2,054.9 +/- 1,773.5 pg/mL, p=0.015). The number of transferable embryos was also significantly higher in Group B (2.9 +/- 1.7 vs. 3.7 +/- 2.0, p=0.027). There was no statistically significant difference in the outcomes such as the dose of gonadotropins administered, the number of oocytes retrieved, and the clinical pregnancy rate. CONCLUSION: GnRH agonist long protocol with the reduced dose from half-dose at the start to 1/3 or 1/4 of dose after pituitary suppression may be more beneficial for COH in IVF-ET patients with high basal serum FSH level. Further prospective randomized controlled study in a larger scale will be necessary to confirm this findings.

Clinical Efficacy and Hormonal Change of GnRH Antagonist in Controlled Ovarian Stimulation for IVF-ET / 대한불임학회지

OBJECTIVES: To evaluate the efficacy of GnRH antagonist cetrorelix in women undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) and to determine changes in serum hormone concentrations during cetrorelix administration. METHODS: We performed a clinical trial on 30 patients undergoing COH with highly purified follicular stimulating hormone (HP-FSH) and gonadotropin releasing hormone antagonist (GnRHant), cetrorelix. FSH was administrated from day 2 or 3 of cycle with fixed dose and adjusted according to individual response. 0.25 mg of cetrorelix was injected daily subcutaneously from stimulation day 5 until the day of hCG administration. Daily ultrasound monitoring was performed for growing follicles and serum levels of luteinizing hormone (LH), estradiol (E2) and progesterone were measured daily during cetrorelix administration. Up to 4 embryos were transferred. RESULTS: Mean age of enrolled patients was 32.0+/-3.4 years (mean +/-S.D.). All of 30 patients underwent oocyte pick-up, and embryo transfer was done in 28 patients. The total and mean numbers of received oocytes were 196 and 6.5+/-4.7, the number of fertilized eggs was 111, and the fertilization rate was 56.6%. Total duration of FSH administration was 9.2+/-2.2 days and mean of 24.3+/-7.7 ampules of HP-FSH was administered. Total duration of cetrorelix administration was 5.7+/-1.9 days. Serum LH and progesterone levels were maintained in the range of 1.4~2.9 mIU/mL and 0.3~0.6 ng/ mL, which respectively reflected effective prevention of premature LH surge. Clinical pregnancies were achieved in 9 patients, and overall clinical pregnancy rate was 30.0% per oocyte retrieval, and 32.1% per embryo transfer. CONCLUSION: GnRH antagonist is safe and convenient for COH for IVF-ET and effective with optimal pregnancy rate.

Efficacy of Gonadotropin-releasing Hormone Antagonist and Agonist in Controlled Ovarian Hyperstimulation in IVF-ET Patients with Expected Normal Ovarian Response / 대한산부인과학회잡지

OBJECTIVE: To assess the efficacy of GnRH antagonist in controlled ovarian hyperstimulation (COH) for IVF-ET compared with GnRH agonist in infertile patients who are expected to have normal ovarian response. METHODS: This study reviewed 105 cycles of 105 women who underwent IVF-ET for the first time in SNUH from January, 2001 to October, 2003. In the study group (n=51), a daily dose of 0.25 mg of GnRH antagonist (cetrorelix or ganirelix) was administered beginning when leading follicles reached mean diameter of 13-14 mm and continued until the day of hCG injection. In the control group (n=54), patients were first desensitized with GnRH agonist (triptorelin) long protocol, which was continued during the gonadotropins treatment until the day of hCG injection. The outcome parameters of COH and IVF-ET were compared retrospectively between the two groups. Statistical analysis was performed using Student's t-test for the comparison of means, and the chi-square test where appropriate. Statistical significance was defined as p<0.05. RESULTS: General characteristics of the patients in respect to age, parity, body mass index of the two groups were comparable. In the study group, there were significant reduction in the dosages of gonadotropins used (1818.1 +/- 812.3 IU vs. 2420.2 +/- 839.2 IU)and the duration of COH (8.9 +/- 2.1 days vs. 10.9 +/- 1.6 days). The mean serum level of estradiol and endometrial thickness on hCG day were significantly lower in the study group. Number of embryos transferred and CES (cumulative embryo score) were significantly lower in the study group compared to the control group. However there were no significant differences in the number of oocytes retrieved, the fertilization, implantation, and clinical pregnancy rates, and the incidence of OHSS between the two groups. CONCLUSION: For patients who are expected to have normal ovarian response, a GnRH antagonist multiple dose protocol in flexible fashion can be used as a protocol of choice in COH for IVF-ET. This protocol showed comparable pregnancy rate as GnRH agonist long protocol. However, the mean number of gonadotropin ampules administered and the mean number of stimulation days were significantly less in the GnRH antagonist group optimizing the convenience for the patients.

Clinical Efficacy of Serum Insulin-like Growth Factor- I (IGF-I), IGF-II, and IGF Binding Protein-3 (IGFBP-3) in Predicting the Prognosis of In Vitro Fertilization and Embryo Transfer / 대한산부인과학회잡지

OBJECTIVE: To evaluate the clinical efficacy of serum insulin-like growth factor-I (IGF-I), IGF-II, and IGF binding protein-3 (IGFBP-3) levels in predicting the prognosis of in vitro fertilization and embryo transfer (IVF-ET). MATERIALS AND METHODS: In 84 patients undergoing IVF-ET, serum levels of IGF-I , IGF-II, and IGFBP-3 were measured using immunoradiometric assay (IRMA) before the gonadotropin administration and on the hCG day of controlled ovarian hyperstimulation (COH). Serum levels of IGFs and IGFBP-3, and the outcomes of IVF-ET were retrospectively analyzed and compared between the pregnant (n=18) and nonpregnant (n=66) groups. RESULTS: There were no significant differences in the outcomes of COH such as total dosage of gonadotropins used, duration of COH, serum estradiol (E2) level on the hCG day, numbers of oocytes retrieved and fertilized, and number of embryos transferred between the pregnant and nonpregnant groups. No differences were found in serum levels of IGF- I , IGF-II, and IGFBP-3, and their ratios before the gonadotropin administration and on the hCG day of COH. Basal serum level of IGF-II was lower with the borderline significance in the pregnant group (796.9+/-159.6 vs. 908.9+/-338.9 ng/ml, p=0.056). The ratio of change in IGF-I to that of IGF-II was significantly higher in the pregnant group (0.066+/-0.489 vs. -0.582+/-2.091, p=0.045). CONCLUSION: Even though basal serum level of IGF-II was lower and the ratio of changes in IGF-I to IGF-II was higher in the pregnant group, serum levels of IGF-I , IGF-II, and IGFBP-3 do not seem to predict the prognosis of IVF-ET. Further investigations are necessary in a larger group of patients to elucidate the clinical efficacy of serum IGFs and IGFBPs levels in predicting the prognosis of IVF-ET.

GnRH Antagonist Multiple Dose Protocol in Controlled Ovarian Hyperstimulation for In Vitro Fertilization and Embryo Transfer Compared with GnRH Agonist Long Protocol / 대한산부인과학회잡지

OBJECTIVE: To evaluate the efficacy of GnRH antagonist multiple dose protocol (MDP) in controlled ovarian hyperstimulation (COH) for in vitro fertilization and embryo transfer (IVF-ET) comparing with the standard GnRH agonist long protocol (GnRH-a LP). METHODS: From January 2000 to September 2002, 57 infertile women with tubal factor alone who had undergone IVF-ET were enrolled in the present study. Study group consisted of 28 patients in 28 cycles in which GnRH antagonist Cetrorelix 0.25 mg was given daily when the leading follicle reached 14 mm in mean diameter until the human chorionic gonadotropin (hCG) injection. Control group consisted of 29 patients in 29 cycles in which COH was performed using standard GnRH-a luteal LP. RESULTS: Patient's characteristics were comparable in both groups. Premature luteinization was not developed in all patients in each group. The number of ampules and duration of exogenous gonadotropins required were significantly lower in the study group than those in the control group (por=14 mm diameter on the day of hCG injection, the number of oocytes retrieved, fertilization rate, and the number of grade I, II embryos between the two groups, but the numbers of mature oocytes retrieved and fertilized oocytes were significantly lower in the study group than in the control group (p<0.01, p<0.01). The clinical pregnancy rate seemed to be lower in the study group, but the difference did not achieve significance (28.6% vs 34.5%). There were also no differences in the miscarriage rate and multiple pregnancy rate between the two groups. CONCLUSION: This study demonstrates that GnRH antagonist Cetrorelix MDP can result in the comparable pregnancy outcome as the GnRH-a LP and furthermore reduce the total dose of gonadotropins and duration of stimulation.

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.