OBJECTIVE: To investigate the correlation between soluble receptor for advanced glycation end products (sRAGE) level in the follicular fluid and ovarian responsiveness in non-PCOS patients undergoing controlled ovarian hyperstimulation. METHODS: Ninety non-PCOS patients underwent IVF/ICSI using a short-acting long protocol for ovarian stimulation with a GnRH agonist. For each patient, the level of sRAGE in the follicular fluid was measured by enzyme linked immunosorbent assay (ELISA), and the data including the clinical baseline state, hormone level, number of oocytes obtained and the fertilization rate were collected. RESULTS: Follicular fluid sRAGE level showed significant negative correlations with basal FSH level (=0.0036) and Gn dose ( < 0.0001) and positive correlations with AFC ( < 0.0001), number of oocytes obtained ( < 0.0001), and the fertilization rate (=0.0047). Follicular fluid sRAGE level was positively correlated with the number of oocytes obtained, and was significantly higher in cases with oocytes obtained above the target number (> 15) than in cases with oocytes obtained within the range of the target numbers (7-15) and below the target number (< 7) ( < 0.0001 and =0.0012, respectively). CONCLUSIONS Follicular fluid sRAGE level can reflect ovarian reserve function in non-PCOS patients, the number of oocytes obtained and the fertilization rate, and can thus predict ovarian responsiveness during controlled hyperstimulation in nonPCOS patients.
Female ; Fertilization in Vitro ; Follicular Fluid ; Humans ; Ovarian Hyperstimulation Syndrome ; Receptor for Advanced Glycation End Products

OBJECTIVE: To compare the clinical pregnancy rate (CPR) and ongoing pregnancy rate (OPR) in frozen embryo transfers (FETs) following either freeze-all policy to prevent ovarian hyperstimulation syndrome (OHSS; freeze-all group) or excess embryo cryopreservation after fresh embryo transfer (surplus group). METHODS: The freeze-all group comprised 44 FET cycles performed in 25 women between 2010 and 2016. The surplus group comprised 53 FET cycles performed in 47 women during the same period. The cumulative CPR and OPR according to duration of cryopreservation (interval between cryopreservation and FET) was estimated using Kaplan-Meier plots. Cox regression analysis was used for identifying factor to affect to cryopreservation duration in cycles with pregnancy. RESULTS: In day 2–4 transfer cycles, the crude CPR (40% vs. 18.2%) and OPR (20% vs. 4.5%) were similar between the 2 groups. In day 5 transfer, the crude CPR (33.3% vs. 38.7%) and OPR (33.3% vs. 29%) were also similar between the 2 groups. The cumulative CPR (100% vs. 47.5%) and OPR (100% vs. 33.3%) in day 2–4 transfer as well as the cumulative CPR (46.7% vs. 100%) and OPR (46.7% and 74.8%) in day 5 transfer were also similar between the 2 groups. The median duration of cryopreservation was significantly shorter in the freeze-all group than in the surplus group (19.8 vs. 36.9 weeks, P=0.04). Previous history of delivery was the only factor associated with a shorter cryopreservation duration in cycles with pregnancy (hazard ratio, 0.18; 95% confidence interval, 0.05–0.65; P=0.01). CONCLUSION: Freezing embryos to prevent OHSS and transferring the frozen embryos later may guarantee an acceptable reproductive outcome.
Cardiopulmonary Resuscitation ; Cryopreservation ; Embryo Transfer* ; Embryonic Structures* ; Female ; Freezing ; Humans ; Ovarian Hyperstimulation Syndrome* ; Pregnancy ; Pregnancy Rate

OBJECTIVE: To prospectively evaluate the efficacy and safety of a fixed early gonadotropin-releasing hormone (GnRH) antagonist protocol compared to a conventional midfollicular GnRH antagonist protocol and a long GnRH agonist protocol for in vitro fertilization (IVF) in patients with polycystic ovary syndrome (PCOS). METHODS: Randomized patients in all three groups (early antagonist, n=14; conventional antagonist, n=11; long agonist, n=11) received 21 days of oral contraceptive pill treatment prior to stimulation. The GnRH antagonist was initiated on the 1st day of stimulation in the early antagonist group and on the 6th day in the conventional antagonist group. The GnRH agonist was initiated on the 18th day of the preceding cycle. The primary endpoint was the number of oocytes retrieved, and the secondary endpoints included the rate of moderate-to-severe ovarian hyperstimulation syndrome (OHSS) and the clinical pregnancy rate. RESULTS: The median total number of oocytes was similar among the three groups (early, 16; conventional, 12; agonist, 19; p=0.111). The early GnRH antagonist protocol showed statistically non-significant associations with a higher clinical pregnancy rate (early, 50.0%; conventional, 11.1%; agonist, 22.2%; p=0.180) and lower incidence of moderate-to-severe OHSS (early, 7.7%; conventional, 18.2%; agonist, 27.3%; p=0.463), especially among subjects at high risk for OHSS (early, 12.5%; conventional, 40.0%; agonist, 50.0%; p=0.324). CONCLUSION: In PCOS patients undergoing IVF, early administration of a GnRH antagonist may possibly lead to benefits due to a reduced incidence of moderate-to-severe OHSS in high-risk subjects with a better clinical pregnancy rate per embryo transfer. Further studies with more subjects are required.
Embryo Transfer ; Female ; Fertilization in Vitro ; Gonadotropin-Releasing Hormone* ; Humans ; Incidence ; Oocytes ; Ovarian Hyperstimulation Syndrome ; Polycystic Ovary Syndrome* ; Pregnancy ; Pregnancy Rate ; Prospective Studies

OBJECTIVE: The purpose of this retrospective study was to evaluate the appropriateness of various follicle-stimulating hormone (FSH) starting doses in expected normal responders based on the nomogram developed by La Marca et al. METHODS: A total of 117 first in vitro fertilization cycles performed from 2011 to 2017 were selected. All women were expected normal responders and used a recombinant FSH and flexible gonadotropin-releasing hormone antagonist protocol. The FSH starting dose was empirically determined (150, 225, or 300 IU). The FSH starting dose indicated by La Marca's nomogram was determined using female age and serum anti-Müllerian hormone or basal FSH levels. If the administered dose was exactly the same as the proposed dose, the cycle was assigned to the concordant group (34 cycles). If not, it was assigned to the discordant group (83 cycles). Optimal ovarian response was defined as a total of 8–14 oocytes, hypo-response as < 8 oocytes, and hyper-response as >14 oocytes. RESULTS: Between the concordant and discordant group, ovarian response (optimal, 32.4% vs. 27.7%; hypo-response, 55.9% vs. 54.2%; and hyper-response, 11.8% vs. 18.1%) and the number of total or mature oocytes were similar. Ovarian hyperstimulation syndrome was rare in both groups (0% vs. 1.2%). The implantation rate, clinical pregnancy rate, miscarriage rate, and live birth rate were all similar. CONCLUSION: The use of the proposed FSH starting dose determined using La Marca's nomogram did not enhance the optimal ovarian response rate or pregnancy rate in expected normal responders. Individualization of the FSH starting dose by La Marca's nomogram appears to have no distinct advantages over empiric choice of the dose in expected normal responders.
Abortion, Spontaneous ; Female ; Fertilization in Vitro* ; Follicle Stimulating Hormone* ; Gonadotropin-Releasing Hormone ; Humans ; In Vitro Techniques* ; Live Birth ; Nomograms ; Oocytes ; Ovarian Hyperstimulation Syndrome ; Pregnancy ; Pregnancy Rate ; Retrospective Studies*

OBJECTIVE: Hyperstimulation methods are broadly used for in vitro fertilization (IVF) in patients with infertility; however, the side effects associated with these therapies, such as ovarian hyperstimulation syndrome (OHSS), have not been well studied. N-glycoproteomes are subproteomes used for the remote sensing of ovarian stimulation in follicular growth. Glycoproteomic variation in human follicular fluid (hFF) has not been evaluated. In this study, we aimed to identify and quantify the glycoproteomes and N-glycoproteins (N-GPs) in natural and stimulated hFF using label-free nano-liquid chromatography/electrospray ionization-quad time-of-flight mass spectrometry. METHODS: For profiling of the total proteome and glycoproteome, pooled protein samples from natural and stimulated hFF samples were selectively isolated using hydrazide chemistry to obtain the total proteomes and glycoproteomes. N-GPs were validated by the consensus sequence N-X-S/T (92.2% specificity for the N-glycomotif at p<0.05). All data were compared between natural versus hyperstimulated hFF samples. RESULTS: We detected 41 and 44 N-GPs in the natural and stimulated hFF samples, respectively. Importantly, we identified 11 N-GPs with greater than two-fold upregulation in stimulated hFF samples compared to natural hFF samples. We also validated the novel N-GPs thyroxine-binding globulin, vitamin D-binding protein, and complement proteins C3 and C9. CONCLUSION: We identified and classified N-GPs in hFF to improve our understanding of follicular physiology in patients requiring assisted reproduction. Our results provided important insights into the prevention of hyperstimulation side effects, such as OHSS.
Chemistry ; Complement System Proteins ; Consensus Sequence ; Female ; Fertilization in Vitro* ; Follicular Fluid* ; Humans* ; In Vitro Techniques* ; Infertility ; Mass Spectrometry ; Ovarian Hyperstimulation Syndrome ; Ovulation Induction ; Physiology ; Proteome ; Proteomics ; Reproduction ; Sensitivity and Specificity ; Thyroxine-Binding Globulin ; Up-Regulation ; Vitamin D-Binding Protein

The purpose of this paper is to assimilate all data pertaining to the use of gonadotropin-releasing hormone (GnRH) antagonists in in vitro fertilization cycles after ovulation trigger to reduce the symptoms of ovarian hyperstimulation syndrome (OHSS). A systematic review of the literature was performed to identify all studies performed on the use of a GnRH antagonist in IVF cycle post-ovulation trigger with patients at high risk for OHSS. Ten studies were identified and reviewed. Descriptions of the studies and their individual results are presented in the following manuscript. Due to significant heterogeneity among the studies, it was not possible to perform a group analysis. The use of GnRH antagonists post-ovulation trigger for treatment of OHSS has been considered for almost 20 years, though research into its use is sparse. Definitive conclusions and recommendations cannot be made at this time, though preliminary data from these trials demonstrate the potential for GnRH antagonists to play a role in the treatment of OHSS in certain patient populations.
Female ; Fertilization in Vitro ; Gonadotropin-Releasing Hormone* ; Humans ; Ovarian Hyperstimulation Syndrome* ; Ovulation ; Population Characteristics

No abstract available.
Female ; Female* ; Humans ; Hypothyroidism* ; Lingual Thyroid* ; Ovarian Hyperstimulation Syndrome*

No abstract available.
Female ; Female* ; Humans ; Hypothyroidism* ; Lingual Thyroid* ; Ovarian Hyperstimulation Syndrome*

OBJECTIVE: To report an efficacy of gonadotropin releasing hormone (GnRH) antagonist administration after freezing of all embryos for treatment of early type ovarian hyperstimulation syndrome (OHSS). METHODS: In 10 women who developed fulminant early type OHSS after freezing of all embryos, GnRH antagonist (cetrorelix 0.25 mg per day) was started at the time of hospitalization and continued for 2 to 4 days. Fluid therapy and drainage of ascites was performed as usual. RESULTS: Early type OHSS was successfully treated without any complication. At hospitalization, the median (95% confidence interval [CI]) of the right and the left ovarian diameter was 10.0 cm (7.6 to 12.9 cm) and 8.5 cm (7.5 to 12.6 cm). After completion of GnRH antagonist administration, it was decreased to 7.4 cm (6.2 to 10.7 cm) (P=0.028) and 7.8 cm (5.7 to 12.2 cm) (P=0.116), respectively. The median duration of hospital stay was 6 days (3 to 11 days). Trans-abdominal drainage of ascites was performed in 2 women and drainage of ascites by percutaneous indwelling catheter was performed in 4 women. No side effect of GnRH antagonist was noted. CONCLUSION: GnRH antagonist administration appears to be safe and effective for women with fulminant early type OHSS after freezing all embryos. Optimal dose or duration of GnRH antagonist should be further determined.
Ascites ; Catheters, Indwelling ; Drainage ; Embryonic Structures ; Female ; Fluid Therapy ; Freezing ; Gonadotropin-Releasing Hormone* ; Gonadotropins* ; Hospitalization ; Humans ; Length of Stay ; Ovarian Hyperstimulation Syndrome*

OBJECTIVE: The purpose of this study was to identify useful clinical factors for the identification of patients with polycystic ovary syndrome (PCOS) who would benefit from in vitro maturation (IVM) treatment without exhibiting compromised pregnancy outcomes. METHODS: A retrospective cohort study was performed of 186 consecutive patients with PCOS who underwent human chorionic gonadotropin-primed IVM treatment between March 2010 and March 2014. Only the first IVM cycle of each patient was included in this study. A retrospective case-control study was subsequently conducted to compare pregnancy outcomes between IVM and conventional in vitro fertilization (IVF) cycles. RESULTS: Through logistic regression analyses, we arrived at the novel finding that serum anti-Müllerian hormone (AMH) levels and the number of fertilized oocytes in IVM were independent predictive factors for live birth with unstandardized coefficients of 0.078 (95% confidence interval [CI], 1.005-1.164; p=0.037) and 0.113 (95% CI, 1.038-1.208; p=0.003), respectively. Furthermore, these two parameters were able to discriminate patients who experienced live births from non-pregnant IVM patients using cut-off levels of 8.5 ng/mL and five fertilized oocytes, respectively. A subsequent retrospective case-control study of patients with PCOS who had serum AMH levels ≥8.5 ng/mL showed that IVM had pregnancy outcomes comparable to conventional IVF, and that no cases of ovarian hyperstimulation syndrome were observed. CONCLUSION: Serum AMH levels are a useful factor for predicting pregnancy outcomes in PCOS patients before the beginning of an IVM cycle. IVM may be an alternative to conventional IVF for PCOS patients if the patients are properly selected according to predictive factors such as serum AMH levels.
Case-Control Studies ; Chorion ; Cohort Studies ; Female ; Fertilization in Vitro ; Humans ; In Vitro Oocyte Maturation Techniques ; In Vitro Techniques* ; Live Birth ; Logistic Models ; Oocytes ; Ovarian Hyperstimulation Syndrome ; Polycystic Ovary Syndrome* ; Pregnancy ; Pregnancy Outcome ; Pregnancy Rate ; Retrospective Studies