Hyperstimulation For In Vitro Fertilization Research Articles

Impact of Controlled Ovarian Hyperstimulation on Thyroid Function

OBJECTIVE: To compare the effects of different protocols of controlled ovarian hyperstimulation on thyroid function with those of the natural menstrual cycle. STUDY DESIGN: Prospective controlled study. SETTING: University Medical Center. PATIENTS: A total of 97 women without a history of endocrine disease undergoing intrauterine insemination either in a natural cycle, or with mild ovarian hyperstimulation, or in vitro fertilization (IVF). MAIN OUTCOME MEASURES: estradiol (E2), thyroxine binding globulin (TBG), free thyroxine (FT4), total thyroxine (TT4) and thyroid stimulating hormone (TSH) during the midluteal phase. RESULTS: In the IVF group midluteal E₂, TBG, and TT₄ were significantly higher; midluteal FT₄ was significantly lower (mean difference: -1.46 pmol/L; P < 0.001) and midluteal TSH was significantly higher (mean difference: 0.52 mU/L; P = 0.015). CONCLUSIONS: Ovarian hyperstimulation in IVF is associated with lower midluteal FT₄ and higher midluteal TSH levels compared to the natural cycle.

A prospective randomized comparison of routine buserelin acetate and a decreasing dosage of nafarelin acetate with a low-dose gonadotropin-releasing hormone agonist protocol for in vitro fertilization and intracytoplasmic sperm injection

Objective: To compare the efficacy of a draw-back nafarelin acetate protocol with routine buserelin acetate administration for in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Design: Prospective clinical study. Setting: Mie University School of Medicine, Tsu, Mie, Japan. Patient(s): One hundred sixty-nine women treated with IVF and 183 women treated with ICSI. Intervention(s): Nafarelin acetate and buserelin acetate in ovarian hyperstimulation in IVF and ICSI were administered. Main Outcome Measure(s): The concentrations of estradiol (E 2), FSH, LH, gonadotropin dosages; the number of oocytes retrieved, oocytes fertilized, and embryos; and pregnancy rates. Result(s): A prospective study was conducted with 44 cycles for 34 couples with nafarelin acetate (group 1) and 47 cycles for 40 couples with buserelin acetate (group 2) with a long IVF protocol; 68 cycles for 46 couples with nafarelin acetate (group 3) and 56 cycles for 39 couples with buserelin acetate (group 4) with a short IVF protocol; 39 cycles for 32 couples with nafarelin acetate (group 5) and 50 cycles for 30 couples with buserelin acetate (group 6) with a long ICSI protocol; and 87 cycles for 60 couples with nafarelin acetate (group 7) and 81 cycles for 61 couples with buserelin acetate (group 8) with a short ICSI protocol. Patients were randomized to receive either full-dose nafarelin acetate (200 μg b.i.d.) treatment for 7 days followed by half-dose nafarelin acetate (200 μg daily) or buserelin acetate (300 μg t.i.d.). There were no statistically significant differences in baseline concentrations of E 2 and FSH, concentrations of E 2, P4, FSH, LH on hCG administration, gonadotropin dosage, the number of oocytes retrieved and embryos transferred, or pregnancy rates between groups 1 and 2, groups 3 and 4, groups 5 and 6, and groups 7 and 8. Conclusion(s): Full-dose nafarelin acetate treatment for 7 days followed by half-dose nafarelin acetate (“draw-back” protocol) is an effective new protocol for IVF and ICSI.

Circulatory Dysfunction in Asymptomaticin VitroFertilization Patients. Relationship with Hyperestrogenemia and Activity of Endogenous Vasodilators1

Severe ovarian hyperstimulation syndrome (OHSS) is consistently associated with a circulatory dysfunction characterized by arterial hypotension, low peripheral vascular resistance, and increased activity of the renin-aldosterone system. To investigate whether circulatory dysfunction also occurs in asymptomatic patients undergoing controlled gonadotropin ovarian hyperstimulation under pituitary suppression for in vitro fertilization (IVF), 12 women without clinical manifestations of OHSS underwent sequential blood, urine, and hemodynamic measurements at five study points: the 7th day of the menstrual cycle preceding IVF (study point 1 or baseline), the day when pituitary suppression was shown (study point 2), the day of hCG ovulatory injection (study point 3), the day after hCG was injected (study point 4), and 7 days after hCG administration (study point 5). Mean arterial pressure, cardiac output, peripheral vascular resistance, plasma concentrations of estradiol (E2) and aldosterone, and plasma renin activity (PRA) were measured at each study point in all women. Serum levels of nitrite/nitrate, and plasma concentration of atrial natriuretic peptide, norepinephrine, adrenomedullin, and cyclic guanosine 3'5'-monophosphate were measured in samples obtained at study points 1 and 5. Multiple follicular development during ovarian stimulation associated with increased plasma E2 concentration (mean peak plasma E2 level, 2430 +/- 428 pg/mL, range 1630-3840 pg/mL) were observed in each woman. All patients developed a significant increase in cardiac output and decrease in arterial pressure and peripheral vascular resistance, and a marked elevation in PRA and aldosterone, all indicating the development of arteriolar vasodilation. Changes in circulatory measurements were temporarily related with the increase in E2 both being detected at study points 3-5. In contrast, there was a clear chronological dissociation between the increase in plasma E2 concentration and the stimulation of the renin-aldosterone system. PRA and aldosterone only reached abnormal levels at study point 5 in association with a significant increase in plasma norepinephrine concentration. Serum levels of nitrite/nitrate and plasma concentrations of atrial natriuretic peptide, adrenomedullin, and cyclic GMP were similar at study points 1 and 5. It is concluded that the circulatory dysfunction that characterizes severe OHSS is a universal event in patients undergoing controlled ovarian hyperstimulation for IVF. Although the increase in E2 levels during IVF cycles is associated with significant circulatory changes, the circulatory dysfunction that characterizes severe OHSS is clearly unrelated to the onset of hyperestrogenemia. Arteriolar vasodilation during IVF cycles was not associated with an increased activity of the vasodilator substances atrial natriuretic peptide, adrenomedullin, and nitric oxide.

Are there predictive criteria of complicated ovarian hyperstimulation in IVF?

Among 599 trials of in-vitro fertilization (IVF) treatment, complicated ovarian hyperstimulation (OHSS) was diagnosed in 14 cases (2.5%) on the basis of heavy abdominal discomfort and echographic findings (ascites, ovarian enlargement with cysts). Among eight hospitalized patients, four presented with a haemoconcentration and/or electrolytic disturbances. OHSS cases were compared with two control groups for a series of criteria: age, aetiology of infertility, total dose of human menopausal gonadotrophin (HMG), day of oocyte collection, oestradiol (E2) peak level, rate of E2 increase, number of oocytes, number of embryos transferred and embryonic vitality scores. Comparison with a random group of normal IVF trials showed a significant difference for the following parameters: E2 peak level and rate of increase, E2/dose of HMG, E2/day of egg collection and number of oocytes. When OHSS cases were compared to another control group consisting only of high E2 responders (peak E2 greater than 2700 pg/ml), no significant difference was found for any of the above-mentioned criteria. In view of this lack of predictive power of individual criteria, stepwise discriminant analysis was applied, showing that this method might provide a predictive mathematical function for evaluating the risk of OHSS before human chorionic gonadotrophin (HCG) administration. Such a formula, however, should be validated by a multicentric study in which a greater number of OHSS cases would be tested.

The advantages of a gonadotropin releasing hormone agonist (leuprolide acetate) in conjunction with gonadotropins for controlled ovarian hyperstimulation in IVF and GIFT cycles

Since the incorporation of gonadotropin releasing hormone agonists (GnRHa) in controlled ovarian hyperstimulation (COH) regimes with various combinations of gonadotropins, there is evidence that specific advantages are obtained from using these agonists in invitro fertilization (IVF) and gamete intrafallopian tube transfer (GIFT) procedures. There is evidence that the increased efficiency rate in terms of pregnancy per IVF & GIFT cycle initiated, stems largely, from a reduced treatment cycle cancellation rate prior to oocyte harvest due to a relative increase in follicle stimulating hormone (FSH) to luteinizing hormone (LH) concentration and the inhibition of a preovulatory LH rise, resulting in improved follicle growth, endocrine responses and more healthy oocytes available for fertilization.