PURPOSE: To elucidate the correlation between ovarian reserve and the incidence of ectopic pregnancy (EP) following in vitro fertilization and embryo transfer (IVF/ET) cycles. MATERIALS AND METHODS: In this observational study, 430 fresh IVF/ET cycles were examined from patient data of two university hospital infertility clinics. All included patients were positive for β-human chorionic gonadotropin (hCG) at 2 weeks after oocyte retrieval via controlled ovarian stimulation. For each cycle, information on age, duration of infertility, basal follicle stimulating hormone (FSH), anti-Müllerian hormone (AMH), days of ovarian stimulation, numbers of retrieved oocytes and transferred embryos, and pregnancy outcomes was collected. Patients with AMH lower than 1.0 ng/dL or basal FSH higher than 10 mIU/mL were classified into the decreased ovarian reserve (DOR) group, and the remaining patients were classified into the normal ovarian reserve (NOR) group. RESULTS: In total, 355 cycles showed NOR, and 75 cycles DOR. There were no significant differences between the DOR and NOR groups regarding intrauterine (74.7% vs. 83.4%, respectively) or chemical (14.7% vs. 14.1%, respectively) pregnancies. The DOR group had a higher EP than that of NOR group [10.7% (8/75) vs. 2.5% (9/355), p=0.004]. In both univariate [odds ratio (OR) 5.6, 95% confidence interval (CI) 1.4–9.6, p=0.011] and multivariate (adjusted OR 5.1, 95 % CI 1.1–18.7, p=0.012) analysis, DOR was associated with a higher risk of EP. CONCLUSION: DOR may be associated with a higher risk of EP in IVF/ET cycles with controlled ovarian stimulation. More careful monitoring may be necessary for pregnant women with DOR.
Chorionic Gonadotropin ; Embryo Transfer ; Embryonic Structures ; Female ; Fertilization in Vitro ; Follicle Stimulating Hormone ; Humans ; In Vitro Techniques ; Incidence ; Infertility ; Observational Study ; Oocyte Retrieval ; Oocytes ; Ovarian Reserve ; Ovulation Induction ; Pregnancy ; Pregnancy Outcome ; Pregnancy, Ectopic ; Pregnant Women

OBJECTIVES: We investigated whether luteal estrogen administration and an early follicular Gonadotropin-releasing hormone antagonist (E/G-ant) priming protocol improves clinical outcomes in poor responders to controlled ovarian stimulation for in vitro fertilization (IVF)-embryo transfer, and identified underlying mechanisms. METHODS: This restrospective study consisted of 65 poor responders who underwent the E/G-ant priming protocol. Sixty-four other poor responders undergoing conventional protocols without pretreatment were included as the control group. Clinical outcomes were compared between 2 groups. RESULTS: The E/G-ant priming protocol group exhibited improvements over the control group in terms of the number of retrieved oocytes (3.58±2.24 vs. 1.70±1.45; P=0.000), mature oocytes (2.68±2.11 vs. 1.65±1.23; P=0.000), fertilized oocytes (2.25±1.74 vs. 1.32±1.26; P=0.001), good embryos (1.62±0.91 vs. 1.14±0.90, P=0.021). Day 3 follicle-stimulating hormone (FSH; 8.40±4.84 vs. 16.39±13.56; P=0.000) and pre-ovulation progesterone levels (0.67 vs. 1.28 ng/mL; P=0.016) were significantly higher in the control group than in the E/G-ant priming group. The overall rate of positive human chorionic gonadotropin tests was higher in the E/G-ant priming group than in the control group (32.3% vs.16.1%; P=0.039). Also, clinical pregnancy rate (26.2% vs. 12.5%; P=0.048) and the rate of live births (23.1% vs. 7.1%; P=0.023) were significantly higher in the E/G-ant priming group than in the control group. CONCLUSION: The E/G-ant priming protocol would lead to promising results in poor responders to IVF by suppressing endogenous FSH and by preventing premature luteinization.
Chorionic Gonadotropin ; Embryonic Structures ; Estrogens ; Fertilization in Vitro ; Follicle Stimulating Hormone ; Gonadotropin-Releasing Hormone ; In Vitro Techniques ; Live Birth ; Lutein ; Luteinization ; Oocytes ; Ovulation Induction ; Pregnancy Rate ; Progesterone

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.
Cryopreservation ; Drug Therapy ; Embryo Transfer* ; Embryonic Structures* ; Female ; Fertility ; Fertility Preservation ; Fertilization in Vitro* ; Follicle Stimulating Hormone ; Humans ; In Vitro Techniques* ; Korea ; Live Birth ; Oocytes ; Ovary ; Ovulation Induction ; Pregnancy ; Primary Ovarian Insufficiency ; Radiotherapy ; Rectal Neoplasms ; Transplantation ; Transplants

OBJECTIVE: To identify differences in the expression of the genes for peroxisome proliferator-activated receptor (PPAR)-γ, cyclooxygenase (COX)-2, and the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α in granulosa cells (GCs) from polycystic ovary syndrome (PCOS) patients and controls undergoing controlled ovarian stimulation. METHODS: Nine patients with PCOS and six controls were enrolled in this study. On the day of oocyte retrieval, GCs were collected from pooled follicular fluid. Total mRNA was extracted from GCs. Reverse transcription was performed and gene expression levels were quantified by realtime quantitative polymerase chain reaction. RESULTS: There were no significant differences in age, body mass index, and total gonadotropin dose, except for the ratio of luteinizing hormone to follicle-stimulating hormone between the PCOS and control groups. PPAR-γ and COX-2 mRNA was significantly downregulated in the GCs of PCOS women compared with controls (p=0.034 and p=0.018, respectively), but the expression of IL-6 and TNF-α mRNA did not show significant differences. No significant correlation was detected between the expression of these mRNA sequences and clinical characteristics, including the number of retrieved oocytes, oocyte maturity, cleavage, or the good embryo rate. Positive correlations were found among the PPAR-γ, COX-2, IL-6, and TNF-α mRNA levels. CONCLUSION: Our data may provide novel clues regarding ovarian GC dysfunction in PCOS, and indirectly provide evidence that the effect of PPAR-γ agonists in PCOS might result from alterations in the ovarian follicular environment. Further studies with a larger sample size are required to confirm these proposals.
Body Mass Index ; Cyclooxygenase 2* ; Cytokines* ; Embryonic Structures ; Female ; Follicle Stimulating Hormone ; Follicular Fluid ; Gene Expression ; Gonadotropins ; Granulosa Cells* ; Humans ; Interleukin-6 ; Interleukins ; Luteinizing Hormone ; Oocyte Retrieval ; Oocytes ; Ovulation Induction ; Peroxisomes* ; Polycystic Ovary Syndrome* ; Polymerase Chain Reaction ; PPAR gamma ; Prostaglandin-Endoperoxide Synthases ; Reverse Transcription ; RNA, Messenger ; Sample Size ; Tumor Necrosis Factor-alpha

OBJECTIVE: To determine the preferred regimen for women with adenomyosis undergoing in vitro fertilization (IVF), we compared the IVF outcomes of fresh embryo transfer (ET) cycles with or without gonadotropin-releasing hormone (GnRH) agonist pretreatment and of frozen-thawed embryo transfer (FET) cycles following GnRH agonist treatment. METHODS: This retrospective study included 241 IVF cycles of women with adenomyosis from January 2006 to January 2012. Fresh ET cycles without (147 cycles, group A) or with (105 cycles, group B) GnRH agonist pretreatment, and FET cycles following GnRH agonist treatment (43 cycles, group C) were compared. Adenomyosis was identified by using transvaginal ultrasound at the initial workup and classified into focal and diffuse types. The IVF outcomes were also subanalyzed according to the adenomyotic region. RESULTS: GnRH agonist pretreatment increased the stimulation duration (11.5±2.1 days vs. 9.9±2.0 days) and total dose of gonadotropin (3,421±1,141 IU vs. 2,588±1,192 IU), which resulted in a significantly higher number of retrieved oocytes (10.0±8.2 vs. 7.9±6.8, p=0.013) in group B than in group A. Controlled ovarian stimulation for freezing resulted in a significantly higher number of retrieved oocytes (14.3±9.2 vs. 10.0±8.2, p=0.022) with a lower dose of gonadotropin (2,974±1,112 IU vs. 3,421±1,141 IU, p=0.037) in group C than in group B. The clinical pregnancy rate in group C (39.5%) tended to be higher than those in groups B (30.5%) and A (25.2%) but without a significant difference. CONCLUSION: FET following GnRH agonist pretreatment tended to increase the pregnancy rate in patients with adenomyosis. Further large-scale prospective studies are required to confirm this result.
Adenomyosis* ; Embryo Transfer* ; Embryonic Structures* ; Female ; Fertilization in Vitro ; Freezing ; Gonadotropin-Releasing Hormone* ; Gonadotropins ; Humans ; Oocytes ; Ovulation Induction ; Pregnancy Rate* ; Pregnancy* ; Prospective Studies ; Retrospective Studies ; Ultrasonography

OBJECTIVE: To evaluate the effect of a gonadotropin-releasing hormone (GnRH) antagonist protocol using corifollitropin alfa in women undergoing assisted reproduction. METHODS: Six hundred and eighty-six in vitro fertilization-embryo transfer (IVF)/intracytoplasmic sperm injection (ICSI) cycles were analyzed. In 113 cycles, folliculogenesis was induced with corifollitropin alfa and recombinant follicle stimulating hormone (rFSH), and premature luteinizing hormone (LH) surges were prevented with a GnRH antagonist. In the control group (573 cycles), premature LH surges were prevented with GnRH agonist injection from the midluteal phase of the preceding cycle, and ovarian stimulation was started with rFSH. The treatment duration, quality of oocytes and embryos, number of embryo transfer (ET) cancelled cycles, risk of ovarian hyperstimulation syndrome (OHSS), and the chemical pregnancy rate were evaluated in the two ovarian stimulation protocols. RESULTS: There were no significant differences in age and infertility factors between treatment groups. The treatment duration was shorter in the corifollitropin alfa group than in the control group. Although not statistically significant, the mean numbers of matured (86.8% vs. 85.1%) and fertilized oocytes (84.2% vs. 83.1%), good embryos (62.4% vs. 60.3%), and chemical pregnancy rates (47.2% vs. 46.8%) were slightly higher in the corifollitropin alfa group than in the control group. In contrast, rates of ET cancelled cycles and the OHSS risk were slightly lower in the corifollitropin alfa group (6.2% and 2.7%) than in the control group (8.2% and 3.5%), although these differences were also not statistically significant. CONCLUSION: Although no significant differences were observed, the use of corifollitropin alfa seems to offer some advantages to patients because of its short treatment duration, safety, lower ET cancellation rate and reduced risk of OHSS.
Embryo Transfer ; Embryonic Structures ; Female ; Follicle Stimulating Hormone* ; Gonadotropin-Releasing Hormone* ; Humans ; Infertility ; Luteinizing Hormone ; Oocytes ; Ovarian Hyperstimulation Syndrome ; Ovulation Induction ; Pregnancy Rate ; Reproduction* ; Spermatozoa

OBJECTIVE: To evaluate the effect of second-line conservative surgery on in vitro fertilization (IVF) outcome in comparison with IVF without second-line surgery in infertile women with ovarian endometrioma recurrence after primary conservative surgery. METHODS: In this retrospective cohort study, 121 consecutive IVF/intracytoplasmic sperm injection cycles that were performed after second-line surgery (n=53) or without second-line surgery (control group, n=68) between January 2006 and December 2011 in 121 infertile women with ovarian endometrioma(s) recurrence after primary conservative surgery for moderate to severe endometriosis were included. The two groups were compared in terms of controlled ovarian stimulation and IVF outcomes. RESULTS: There were no differences in patients' characteristics between the two groups. Total dose and days of gonadotropins administered were significantly higher in the second-line surgery group than in the control group (P<0.001, P=0.008). The numbers of oocytes retrieved, mature oocytes and grade 1 or 2 embryos were significantly lower in the second-line surgery group (P=0.007, P=0.001, P<0.001, respectively). Clinical pregnancy rate per cycle and embryo implantation rate were also significantly lower in the second-line surgery group of 24.5% and 11.8% compared with 48.5% and 25.3% in the control group (P=0.008, P=0.005, respectively). CONCLUSION: Ovarian response to controlled ovarian stimulation and IVF outcome after second-line surgery is worse than those in IVF cycles without second-line surgery in infertile women with ovarian endometrioma recurrence after primary surgery for moderate or severe endometriosis.
Cohort Studies ; Embryo Implantation ; Embryonic Structures ; Endometriosis* ; Female ; Fertilization in Vitro* ; Gonadotropins ; Humans ; Oocytes ; Ovulation Induction ; Pregnancy ; Pregnancy Rate ; Recurrence* ; Retrospective Studies ; Spermatozoa

This article reports a case of spontaneous ovarian hyperstimulation syndrome (OHSS) following a thawed embryo transfer cycle. OHSS, a potentially life-threatening condition, is an iatrogenic complication of controlled ovarian stimulation; therefore, it is very important to prevent and treat OHSS during treatment with ovulation-inducing agents. Despite our efforts to prevent OHSS, in this case, severe spontaneous OHSS occurred, which resulted in uncontrolled preterm labor and a preterm delivery and also persisted for 6 weeks after delivery. Freezing all embryos cannot entirely prevent the development of OHSS because OHSS can occur spontaneously. Although spontaneous OHSS remains a rare event, females with a history of OHSS may have an elevated risk for spontaneous OHSS. We suggest closely monitoring cases of pregnancy following thawed embryo transfer for early diagnosis of spontaneous OHSS and the use of conservative management.
Cryopreservation ; Early Diagnosis ; Embryo Transfer* ; Embryonic Structures ; Female ; Fertilization in Vitro ; Freezing ; Humans ; Obstetric Labor, Premature ; Ovarian Hyperstimulation Syndrome* ; Ovulation Induction ; Pregnancy

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

OBJECTIVE: To investigate outcomes of stimulated IVF cycles in which GnRH antagonist was omitted on the ovulation triggering day. METHODS: A total of 86 women who underwent controlled ovarian hyperstimulation with recombinant FSH and GnRH antagonist flexible multiple-dose protocols were recruited and prospectively randomized into the conventional group (group A) or cessation group (group B). The GnRH antagonist, 0.25 mg/day of cetrorelix, was started when the leading follicle reached 14 mm in diameter and was continuously administered until the hCG triggering day (group A, 43 cycles) or until the day before hCG administration (group B, 43 cycles). The maturity of oocytes, fertilization rate, embryo quality, and implantation and clinical pregnancy rates were evaluated. RESULTS: The duration of ovarian stimulation, total dose of gonadotropins, serum estradiol levels on hCG administration day, and number of oocytes retrieved were not significantly different between the two groups. The total dose of GnRH antagonist was significantly lower in group B than group A (2.5+/-0.9 vs. 3.2+/-0.8 ampoules, p<0.05). There was no premature luteinization in any of the subjects. The proportion of mature oocytes and fertilization rate were not significantly different in group B than group A (70.7% vs. 66.7%; 71.1% vs. 66.4%, respectively). There were no significant differences in the implantation or clinical pregnancy rates. CONCLUSION: Our prospective randomized study suggested that cessation of GnRH antagonist on the hCG administration day during a flexible multiple-dose protocol could reduce the total dose of GnRH antagonist without compromising its effects on pregnancy rates.
Embryonic Structures ; Estradiol ; Female ; Fertilization ; Fertilization in Vitro ; Gonadotropin-Releasing Hormone ; Gonadotropins ; Humans ; Lutein ; Luteinization ; Oocytes ; Ovulation ; Ovulation Induction ; Pregnancy ; Pregnancy Rate ; Prospective Studies