OBJECTIVE: To compare the IVF outcomes of mild ovarian stimulation with conventional ovarian stimulation in poor responders. METHODS: From 2004 to 2009, 389 IVF cycles in 285 women showed poor responses (defined as either a basal FSH level > or =12 mIU/mL, or the number of retrieved oocytes < or =3, or serum E2 level on hCG day <500 pg/mL) were analyzed, retrospectively. In total, 119 cycles with mild ovarian stimulation (m-IVF) and 270 cycles with conventional ovarian stimulation (c-IVF) were included. Both groups were divided based on their age, into groups over and under 37 years old. RESULTS: The m-IVF group was lower than the c-IVF group in the duration of stimulation, total doses of gonadotropins used, serum E2 level on hCG day, the number of retrieved oocytes, and the number of mature oocytes. However, there was no significant difference in the number of good embryos, the number of transferred embryos, the cancellation rate, or the clinical pregnancy rate. In the m-IVF group over 37 years old, the clinical pregnancy rate and live birth rate were higher when compared with the c-IVF group, but this result was not statistically significant. CONCLUSION: In poor responder groups, mild ovarian stimulation is more cost effective and patient friendly than conventional IVF. Therefore, we suggest that mild ovarian stimulation could be considered for poor responders over 37 years old.
Embryonic Structures ; Female ; Fertilization in Vitro ; Gonadotropins ; Humans ; Live Birth ; Oocytes ; Ovulation Induction ; Pregnancy Rate ; Retrospective Studies

Heterotopic pregnancy is named when an extrauterine (ectopic) pregnancy coexists with an intrauterine pregnancy simultaneously by many causes such as PID (pelvic inflammatory disease), endometriosis, IUD (intrauterine device), previous pelvic surgery and others. This is very rare in general population, with a range of occurrence estimated between 1:7963 and 1:30000. But recently the incidence has increased as the uses of ARTs (assisted reproductive technologies) including ovulation induction, IVF-ET (in-vitro fertilization and embryo transfer) and GIFT (gamete intrafallopian transfer) increase. Because this has high maternal morbidity, mortality and fetal loss, early diagnosis and proper management is very important. We report a case of heterotopic pregnancy following IVF-ET with a brief review.
Early Diagnosis ; Embryonic Structures ; Endometriosis ; Female ; Fertilization ; Incidence ; Mortality ; Ovulation Induction ; Pregnancy ; Pregnancy, Heterotopic*

The simultaneous existence of intrauterine and extrauterine pregnancies is known as a heterotopic pregnancy. Spontaneous heterotopic pregnancy is a rare event although its incidence has increased since the recent development of treatment of infertile women with ovulation induction or in-vitro fertilization and embryo transfer(IVF-ET).The theoretical rate of this condition was estimated to be approximately 1 in 30,000 pregnancies. The early diagnosis of heterotopic pregnancy is very difficult . So there is a high maternal morbidity and fetal loss. We reported a IVP - ET patient resulting in the successful delivery of live infant at 35weeks of gestational age from intrauterine pregnancy following surgical removal of ruptured concurrent extrauterine pregnancy.
Early Diagnosis ; Embryonic Structures ; Female ; Fertilization ; Gestational Age ; Humans ; Incidence ; Infant ; Ovulation Induction ; Pregnancy ; Pregnancy, Heterotopic*

The purpose of this study is compare IVF cycle outcome in poor responders between clomiphene citrate (CC) stimulated and controlled ovarian hyperstimulation (COH) protocol. A total of 94 patients responding poorly in previous IVF cycles (estradiol<600 pg/ml or less than 3 oocytes retrieved) subsequently underwent either COH (COH group: 122 cycles, 68 patients) or CC-stimulated cycles (CC group: 43 cycles, 26 patients). CC was administered for five consecutive days starting on cycle day 3 at a dose of 100 mg daily. Serial transvaginal ultrasound examination was done from cycle day 8. Urine was collected 3~4 times before hCG injection for the detection of LH surge. The hCG was administered when serum estradiol reached greater than 150 Pg/ml and mean follicle diameter>16 mm. In COH group, ovarian stimulation was done using short protocol (GnRH-a/FSH/HMG/hCG). No difference in age or number of transferred embryos was found between CC group and COH group. COH group had significantly (p<0.05) higher mean peak level of E2 (810+/-112 vs 412+/-55 pg/ml) and greater number of retrieved oocytes (3.0+/-0.2 vs 2.0+/-0.2) than CC group. CC group had significantly embryos (1.8+/-0.2) compared with (2.1+/-0.2) in COH group. However, CC group had higher pregnancy rate than COH group per retrieval [26.9% (7/26) vs 6.2% (6/97)], or per transfer [31.8% (7/22) vs 7% (6/86)]. Although cycle cancellation rate in CC group (48.8%) was higher than that of COH group (21.3%), the pregnancy rate per cycle in CC group was still higher (16.3%) than COH group (4.9%). In addition, implantation rate in CC group was 17.5% (7/40), which was significantly p<0.01) higher than 3.9% (7/180) in COH group. These data suggest that oocyte and embryo quality are lower in COH cycles of poor responders than CC cycles. We suggest that clomiphene citrate stimulated IVF cycle may be more efficient than COH IVF cycle in poor responders in terms of lower costs and higher pregnancy performance.
Clomiphene* ; Embryonic Structures ; Estradiol ; Fertilization* ; Humans ; Oocytes ; Ovulation Induction ; Pregnancy ; Pregnancy Rate ; Ultrasonography

OBJECTIVE: We evaluated the fertilization potential of immature oocytes obtained from controlled ovarian hyperstimulation cycles of patients undergoing ICSI. METHODS: We retrospectively analyzed 463 ICSI cycles containing at least one immature oocyte at oocyte denudation. ICSI was performed on mature oocytes at oocyte denudation (metaphase-II [MII] oocytes) and the oocytes that extruded the first polar body between oocyte denudation and ICSI (MI-MII oocytes). Fertilization and early embryonic development were compared between MII and MI-MII oocytes. To investigate the pregnancy potential of MI-MII oocytes, the pregnancy outcome was analyzed in 24 ICSI cycles containing only immature oocytes at retrieval. RESULTS: The fertilization rate of MI-MII oocytes (37.0%) was significantly lower than that of MII oocytes (72.3%). The rates of delayed embryos and damaged embryos did not significantly differ. Eighty-one immature oocytes were retrieved in 24 cycles that retrieved only immature oocytes and 61 (75.3%) of them were in the MI stage. ICSI was performed on 36 oocytes (59.0%) that extruded the first polar body before ICSI and nine MI-MII oocytes (25.0%) were fertilized. Embryo transfers were performed in five cycles. Pregnancy was observed in one cycle, but it ended in biochemical pregnancy. CONCLUSION: In ICSI cycles, oocytes that extruded the first polar body between denudation and ICSI can be used as a source of oocytes for sperm injection. However, their fertilization and pregnancy potential are lower than that of mature oocytes. Therefore, ovarian stimulation should be performed carefully for mature oocytes obtained at retrieval, especially in cycles with a small number of retrieved oocytes.
Embryo Transfer ; Embryonic Development ; Embryonic Structures ; Female ; Fertilization ; Humans ; Oocytes ; Ovulation Induction ; Polar Bodies ; Pregnancy ; Pregnancy Outcome ; Retrospective Studies ; Sperm Injections, Intracytoplasmic ; Spermatozoa

OBJECTIVES: To investigate the effect of LH receptor in folliculogenesis, we confirm the expression level of LH receptor (LH-R) mRNA in human granulosa cells (GCs) and its expression levels were analyzed by comparison to embryo developmental rate and pregnancy rate. MATERIALS AND METHODS: GCs were obtained at the time of oocyte retrieval from the patients undergoing IVF-ET program. The patients were divided into two groups: Group I (n=20) is poor responder (retrieved oocyte(s)< or =3ea), Group II (n=80) is normal responder (retrieved oocytes>3ea). After the extraction of total RNA, semiquantitative RT-PCR was performed and the expression level of LH-R mRNA was normalized by beta-actin. Statistical analysis was performed by using Chi(2) test, Student's t-test and Pearson correlation. RESULTS: In Group II, the relative values of LH-R mRNA (0.680 vs. 0.463, p<0.005) and pregnancy rate (54.7% vs. 23.1%, p<0.05) were significantly higher than in Group I. Number of retrieved oocyte(s) was gradually increased when the expression of LH-R mRNA was increased (p<0.05). But the quality of retrieved oocyte and transferred embryo were not related with the expression of LH-R mRNA. When the pregnancy rate was compared with FSH only group and FSH combined with hMG group in the ovarian stimulation protocol, FSH combined with hMG group was significantly higher than FSH only group in Group I (37.5% vs. 0%), and the expression of LH-R mRNA was significantly higher in hMG combined group than FSH only group (p<0.05). CONCLUSION: Expression level of LH-R mRNA has important role in ovarian function related with the response to gonadotrophin in human folliculogenesis. Furthermore these data might provide the evidence that additional use of hMG is helpful to poor responders.
Actins ; Embryonic Development ; Embryonic Structures ; Female ; Granulosa Cells ; Humans ; Oocyte Retrieval ; Oocytes ; Ovulation Induction ; Pregnancy Rate ; Pregnancy* ; Receptors, LH* ; RNA ; RNA, Messenger

OBJECTIVE: During stimulated IVF cycles, up to 15% of oocytes are recovered as immature. The purpose of this study was to investigate the trend of oocyte maturity in repeated ovarian stimulation for IVF. METHODS: One hundred forty-eight patients were selected who underwent two consecutive IVF cycles using same stimulation protocol during 2008 to 2010. Ovarian stimulation was performed with FSH and human menopausal gonadotropin and flexible GnRH antagonist protocol in both cycles. Oocyte maturity was assessed according to presence of germinal vesicle (GV) and the first polar body. Immature oocyte was defined as GV stage or metaphase I oocyte (GV breakdown with no visible polar body) and cultured up to 48 hours. If matured, they were fertilized with ICSI. RESULTS: Percentages of immature oocytes were 30.8% and 32.9% (p=0.466) and IVM rates of immature oocytes were 36.2% and 25.7% (p=0.077), respectively. A significant correlation was noted between percentage of immature oocytes in the two cycles (R=0.178, p=0.03). Women with >40% immaturity in both cycles (n=21) showed lower fertilization rate of in vivo matured oocytes (56.4% vs. 72.0%, p=0.005) and lower pregnancy rate (19.0% vs. 27.1%, p=0.454) after the second cycle when compared with women with <40% immaturity (n=70). In both groups, female age, number of total retrieved oocyte and embryos transferred were similar. CONCLUSION: In repeated ovarian stimulation cycles for IVF, the immature oocyte tended to be retrieved repetitively in consecutive IVF cycles.
Embryonic Structures ; Female ; Fertilization ; Gonadotropin-Releasing Hormone ; Gonadotropins ; Humans ; Metaphase ; Oocytes ; Ovulation Induction ; Polar Bodies ; Pregnancy Rate

OBJETIVE: The aim of this study was to evaluate the outcome the GnRH antagonist (Cetrotide) short protocol in controlled ovarian hyperstimulation comparing with GnRH agonist long protocol. MATERIALS AND METHOD: From July 2000 to November 2001, 26 patients, 28 cycles were performed in controlled ovarian hyperstimulation by GnRH antagonist and GnRH agonist. GnRH antagonist (Cetrotide) was administered in 12 patients (14 cycles, Group 1) and GnRH agonist (Lucrin, Sub Q, Group 2) in 14 patients (14 cycles). Ovulation induction was performed by hMG (Pergonal) in group 1, and by Combo (Metrodine HP + Pergonal) in group 2. We compared the fertilization rate, good quality embryo, and clinical pregnancy rate between the two groups. Student-t test and Chi-square were used to determine statistical significance. Statistical significance was defined as p<0.05. RESULTS: Ovarian hyperstimulation syndrome did not occurred in which estradiol (E2) level was 3874+/-809 pg/ml and the number of retrieved oocytes was 18.4+/-2.4. The number of used gonadotropin ampules was significantly decreased in Group 1 (26.0 vs. 33.1, p<0.04). There were no significant difference in the number of preovulatory oocyte (10.6+/-6.9 vs. 10.0+/-6.1), fertilization rate (74.8+/-23.4 vs. 72.2+/-21.8), good quality embryo (58.7+/-23.6 vs. 38.7+/-36.6), and embryo transfer (4.3+/-1.6 vs. 4.4+/-1.6). Although the age of the group 1 was older than the group 2 (34.4 vs. 30.8), there was no significant difference in clinical pregnancy rate (50.0% vs. 57.1%). CONCLUSIONS: We suggest that GnRH antagonist was a safe, effective, and alternative method in the controlled ovarian hyperstimulation, especially in PCOD patients who will be develop the ovarian hyperstimulation syndrome.
Embryo Transfer ; Embryonic Structures ; Estradiol ; Female ; Fertilization ; Gonadotropin-Releasing Hormone* ; Gonadotropins ; Humans ; Oocytes ; Ovarian Hyperstimulation Syndrome ; Ovulation Induction ; Pregnancy Rate

Ovarian hyperstimulation syndrome (OHSS) is a life-threatening iatrogenic complication of ovulation induction. Before ovarian stimulation, identification of patients vulnerable to developing OHSS is necessary. And ovarian stimulation should be started with low doses of gonadotropin or GnRH antagonist protocol. During monitoring of ovarian stimulation with risk of OHSS, coasting, low doses hCG and GnRH agonist for triggering ovulation are considered. If severe OHSS is predicted, cycle cancellation and cryopreservation of all embryos should be considered to reduce late-onset OHSS and morbidity. And metformin and dopamine agonist for reducing OHSS are being proposed as a prophylactic treatment for OHSS.
Cryopreservation ; Dopamine Agonists ; Embryonic Structures ; Female ; Gonadotropin-Releasing Hormone ; Gonadotropins ; Humans ; Metformin ; Ovarian Hyperstimulation Syndrome ; Ovulation ; Ovulation Induction ; Risk Factors

During the past few years much effort has been put into simplifying the clinical man-agement of in-vitro fertilization/embryo transfer cycles. One important step was the intro-duction of transvaginal ultrasound-guided oocyte collection, as previously described. This study describes further simplifications in the clinical management of ovarian stimulation and luteal support, and in-vitro fertilization procedure. During the period from October 1994 to September 1995, two major simplification steps were introduced. All cycles were administe-red with a gonadotrophin-releasing hormone agonist according to a long or short protocol preventing premature LH surge. During period I (Group I, n=62 cycles), closer monitoring by several pelvic ultrasound scans and serum oestradiol was used for monitoring the ovarian stimulation ; HTF media with fetal cord serum was used for insemination, growth and tran-sfer media in IVF-ET procedure ; progesterine in oil was daily used by intramuscular injec-tion for luteal support. During period II(Group II-I, n=71 cycles), only several ultrasound scans were used for monitoring the ovarian cycle ; Medi-cult IVF media containing synthetic serum replacement was used for insemination, growth and transfer media; Progesterine in oil was used daily by intramuscular injection for luteal support. During period III(Group II-II, n=16 cycles), further simplification of the clinical management was introduced by using a intravaginal micronized progesterone(Utrogestan) for luteal support. Retrospective analysis between Group I and Group II showed no differences in the number of oocyte(13.2+/-0.8/14.6+/-1.0), fertilization rate(71.5 %/60.7 %), cleavage rate(63.6 %/57.9 %), number of embryos transfered(5.0+/-0.5/4.5+/-0.5). Ongoing pregnancy rates obta ined from the three groups(Group I, Group II-1, Group II-II) were 25.8 %, 25 % and 40 %, respectively(p=ns). But introduction of minimal monitoring gave a significant reduction in the average number of US measurements in the simplified groups(Group II) compared with the group using the conventional monitoring protocol(Group I)(3.8+/-1.0/8.7+/-2.8, p<0.05). In the above groups, five patients developed severe OHSS but there was no differenc e in the distribution. Conclusively, simplified protocols including minimal follicle monitoring only by US, IVF-ET with Medi-cult IVF media containing synthetic serum replacement and the luteal support with intravaginal micronized progesterone gave a increased efficacy of the clinical phase of IVF treatment without a reduction in the success rate.
Culture Media, Serum-Free ; Embryo Transfer* ; Embryonic Structures* ; Estradiol ; Female ; Fertilization* ; Humans ; Injections, Intramuscular ; Insemination ; Menstrual Cycle ; Oocyte Retrieval ; Ovulation Induction ; Pregnancy Rate ; Progesterone ; Retrospective Studies ; Ultrasonography