Altered osmotic thresholds for arginine vasopressin secretion and thirst during superovulation and in the ovarian hyperstimulation syndrome (OHSS): relevance to the pathophysiology of OHSS

OBJECTIVE: To test the hypothesis that decreases in and maintenance of a new steady state in plasma osmolality and sodium level in ovarian hyperstimulation syndrome (OHSS) are due to altered osmoregulation of arginine vasopressin secretion and thirst. DESIGN: Prospective study. SETTING: IVF-ET program in a university-based assisted reproductive treatment center. PATIENT(S): Eight women undergoing superovulation for IVF-ET and five women with normal menstrual cycles. INTERVENTION(S): Two-hour infusion of 5% saline on day 3 or 4 after hCG administration in patients undergoing IVF or in the early luteal phase in controls. A 5% saline infusion test was done on day 10 after hCG administration in one patient with OHSS and one patient without OHSS, both of whom were undergoing IVF. MAIN OUTCOME MEASURE(S): Comparison of changes in thresholds for thirst and plasma vasopressin to plasma osmolality. Changes in urine osmolality, plasma electrolytes, hemoglobin level, and hematocrit were assessed at baseline and during infusion of 5% saline. RESULT(S): The sensitivity of the changes in arginine vasopressin secretion and thirst after 5% saline infusion was similar in IVF patients on day 3 or 4 after hCG and controls. However, the osmotic threshold was significantly lower by 6 mOsm/kg in IVF patients. By day 10 after hCG, the lower osmotic thresholds for arginine vasopressin secretion and thirst persisted in OHSS, although the sensitivity to arginine vasopressin secretion was markedly reduced. CONCLUSION(S): The osmotic thresholds for arginine vasopressin secretion and thirst are reset to lower plasma osmolality during superovulation for IVF-ET. This new lower body tonicity is maintained until at least day 10 after hCG in OHSS. Decreases in plasma osmolality and plasma sodium levels in OHSS are due to altered osmoregulation rather than electrolyte losses; correction of apparent "electrolyte imbalance" in OHSS is therefore inappropriate.     

Serum leptin concentrations in patients with severe ovarian hyperstimulation syndrome during in vitro fertilization-embryo transfer treatment

OBJECTIVE: To investigate the changes in serum leptin concentration in the conception cycle of severe ovarian hyperstimulation syndrome (OHSS). DESIGN: Prospective longitudinal study of 66 IVF-ET cycles between May 2000 and June 2002. SETTING: Infertility outpatient clinic at a Japanese medical school. PATIENT(S): Infertile patients undergoing IVF-ET cycles at the infertility outpatient clinic were divided into three groups consisting of group 1 (conception-cycle patients with severe OHSS, n = 9), and group 2 (conception cycle, non-OHSS, n = 28), and group 3 (nonconception cycle, non-OHSS, n = 29). INTERVENTION(S): Blood samples were collected at five different periods. Period I, on the first day of ovarian stimulation with FSH; period II, at hCG administration before oocyte retrieval; period III, 7 days after oocyte retrieval; period IV, 14 days after oocyte retrieval; and period V, 21 days after oocyte retrieval. MAIN OUTCOME MEASURE(S): Serum leptin concentration. RESULT(S): The serum leptin concentration was low in the OHSS group compared with that of the non-OHSS groups in all serum samples, with significant levels at periods III (vs. groups 2 and 3; P<.05) and IV (vs. group 3; P<.01). A twofold increase of leptin concentration from period I to period II (P<.05) was observed in all groups. CONCLUSION(S): The change pattern in serum leptin concentration might provide a great contribution to the pathophysiology development of OHSS patients during assisted reproductive treatment.     

Lower levels of inhibin A and pro-alphaC during the luteal phase after triggering oocyte maturation with a gonadotropin-releasing hormone agonist versus human chorionic gonadotropin

OBJECTIVE: To investigate the effect of triggering oocyte maturation with GnRH agonist on corpus luteum function by measuring luteal phase levels of inhibin A and pro-alphaC. DESIGN: Prospective randomized trial. SETTING: In vitro fertilization (IVF) program at a university hospital. PATIENT(S): Infertile women undergoing IVF-ET treatment. INTERVENTION(S): Controlled ovarian hyperstimulation with FSH and GnRH antagonist, triggering of final oocyte maturation with either hCG (n = 8) or GnRH agonist (n = 8), IVF-ET, and collection of blood samples every 2-3 days during the luteal phase. MEASUREMENTS AND MAIN RESULTS: Luteal phase serum levels of inhibin A and pro-alphaC, P, and E(2). RESULT(S): Levels of inhibin A, pro-alphaC, estrogen, and P were significantly lower from day 4 to day 14 after triggering final oocyte maturation by GnRH agonist compared with hCG. Maximal luteal serum inhibin A and pro-alphaC levels were 91.5 +/- 23.6 and 184.1 +/- 23.5 pg/mL in the GnRH agonist-treated women compared with 464.7 +/- 209.1 and 7,351.6 +/- 934.3 pg/mL in women treated with hCG. CONCLUSION(S): Triggering final oocyte maturation with GnRH agonist instead of hCG in IVF cycles dramatically decreases luteal levels of inhibins, reflecting significant inhibition of the corpus luteum function. This effect may explain, at least in part, the mechanism of ovarian hyperstimulation syndrome prevention by the use of GnRH agonist.     

血清雌二醇水平和获卵数对体外受精-胚胎移植治疗结局的影响

目的 探讨体外受精与胚胎移植（IVF－ET）程序中注射人绒毛膜促性腺激素（HCG）日血清雌二醇（E2）水平及获卵数目对其治疗结局的影响。方法 回顾分析2000年2月至2001年1月947个IVF－ET周期的资料。结果 注射HCG日血清E2水平过高、获卵过多者，IVF－ET卵母细胞受精率下降，IVF－ET临床妊娠率从单因素分析，有增高趋势，经多因素Logistic回归分析，排除年龄等干扰因素后，血E2水平及获卵数对IVF－ET临床妊娠的影响无统计学意义。血E2水平过高及获卵过多者，伴随重度OHSS发生率的上升。结论 注射HCG日血E2水平过高及获卵数过多不能预测IVF－ET的临床妊娠。     

Effect of paracentesis of ascitic fluids on urinary output and blood indices in patients with severe ovarian hyperstimulation syndrome

OBJECTIVE: To determine the isolated effect of abdominal paracentesis of ascitic fluid in women with severe OHSS on urine production and blood indices. DESIGN: Retrospective interventional study. SETTING: Gynecology department at the Lis Maternity Hospital, affiliated to Tel Aviv University. PATIENT(S): Thirty women with severe OHSS. INTERVENTION(S): Abdominal paracentesis according to clinical indications. MAIN OUTCOME MEASURE(S): Urinary output, blood urea nitrogen, as well as a complete blood count were measured before and following the procedure. RESULT(S): Urinary output increased from 1890 +/- 128 mL per 24 hours on the day before paracentesis to 2,660 +/- 226 mL per 24 hours after the procedure. Blood urea nitrogen values were 8.9 +/- 0.56 mg/dL and 7.8 +/- 0.53 mg/dL on the days before and after paracentesis, respectively. White blood cell count decreased from 15.4 +/- 1.1 (x 10(3) cells/mm(3)) on the days before the paracentesis to 13.3 +/- 0.9 (x 10(3) cells/mm(3)) after the procedure. Hematocrit was reduced significantly from 35.2 +/- 1.0% before the paracentesis to 33.4 +/- 0.8% after paracentesis. CONCLUSION(S): Paracentesis of ascitic fluids in women with severe OHSS has an isolated effect in improving renal function, as is evident by the increased urinary output and reduced blood urea nitrogen.     

Relationship of baseline ovarian volume to ovarian response in World Health Organization II anovulatory patients who underwent ovulation induction with gonadotropins

OBJECTIVE: To assess whether ovarian volume of World Health Organization II anovulatory patients in the early follicular phase predicts the response to ovulation induction with gonadotropins. DESIGN: Retrospective data analysis of two prospective, randomized, multicenter studies. SETTING: Clinical development unit of biotechnology company. PATIENT(S): Four hundred sixty-five World Health Organization II anovulatory patients undergoing ovulation induction. MAIN OUTCOME MEASURE(S): Ovarian response to stimulation, ovulation (mid-luteal serum progesterone > 30 nmol/L), cancellation rate, pregnancy rate, and incidence of the ovarian hyperstimulation syndrome (OHSS) according to baseline ovarian volume (day 2-5) before stimulation. RESULT(S): Mean ovarian volume was 11.55 +/- 6.0 cm(3) (range, 0.8-49.3 cm(3)). Small ovarian volume was associated with lower rates of cycle cancellation owing to risk for OHSS (3 vs. 29 patients [2.8% vs. 9%]). Patients with small ovarian volume (<7.25 cm(3)) required fewer ampules of FSH (1373 IU vs. 1629 IU) and shorter duration of stimulation (16 vs. 18.1 days) and had higher ovulation rate than did patients with mid-range and larger ovarian volume (84.3% vs. 69.1% and 68.8%, respectively). The clinical pregnancy rate per cycle of hCG administration was similar in the three groups (25.8%, 28.1%, and 27.5%). CONCLUSIONS: World Health Organization II anovulatory women with medium-sized or large ovaries who are undergoing low-dose gonadotropin stimulation for ovulation induction may have higher risk for OHSS than do women with small ovaries. Women with small ovaries who meet criteria for administration of hCG respond better to ovulation induction and have a similar likelihood of conceiving compared with women with larger ovaries.     

The midluteal decline in serum estradiol levels is drastic but not deleterious for implantation after in vitro fertilization and embryo transfer in patients with normal or high responses

OBJECTIVE: To determine the impact of the peak E(2) level and its midluteal decline on IVF-ET outcome in a group of normal- and high-responding patients. DESIGN: Retrospective analysis of IVF-ET data. SETTING: Tertiary-care, university-affiliated teaching hospital. PATIENT(S): A total of 100 patients aged 98% E(2) decline; however, the difference did not reach statistical significance. CONCLUSION(S): Multifactorial analysis refutes the negative role of supraphysiologic levels of E(2) on the day of hCG administration or its dramatic decline at the midluteal phase on the success rate after embryo transfer. A possibly increased rate of early spontaneous abortion in the high-response group warrants further verification.     

Successful Pregnancies in Patients with Estrogenic Anovulation After Low-Dose Human Chorionic Gonadotropin Therapy Alone Following hMG for Controlled Ovarian Hyperstimulation

Objective: To demonstrate that folliculogenesis can be sustained with 200 IU human chorionic gonadotropins (hCG) after FSH-priming and result in pregnancy in women with estrogenic ovulatory dysfunction and risk factors for severe ovarian hyperstimulation syndrome (OHSS).Design: Case report: Three women with infertility associated with estrogenic ovulatory dysfunction and hyperinsulinemia who appeared to be at high risk for severe OHSS during gonadotropin therapy.Interventions: After 10 days of receiving either 150 IU hMG or recombinant FSH, patients were switched to 200 IU hCG/day alone for 2–3 days. 5,000 IU of hCG was then administered followed by either home intercourse, intrauterine insemination or transvaginal oocyte retrieval-embryo transfer.Main Outcome Measures: Endovaginal ultrasound measurement of follicle number and size, serum estradiol levels, symptoms of ovarian hyperstimulation, pregnancy test, and evaluation of pregnancy by transvaginal ultrasound.Results: After discontinuation of hMG or recombinant FSH, serum estradiol concentrations continued to rise, and follicles > 14 mm continued to grow during low-dose hCG administration. All women conceived without developing symptoms of OHSS. Pregnancy outcomes achieved include a term singleton delivery, a term twin delivery, and triplets delivered at 31 weeks gestation.Conclusion: The use of low-dose hCG alone is sufficient for supporting the late stages of folliculogenesis in women with estrogenic ovulatory dysfunction. This ovulation induction regimen appears to support the follicular growth of larger follicles while decreasing the number of smaller preovulatory follicles, thereby reducing a known risk factor for OHSS. We report on the positive pregnancy outcomes in 3 women with estrogenic ovulatory dysfunction and clinically appeared to be at high risk for developing severe OHSS who safely underwent this protocol.     

The same luteinized granulosa-luteal cells from normal and superovulated human chorionic gonadotropin (hCG)-stimulated cycles contain hCG and insulin-like growth factor binding protein-1

OBJECTIVE: To determine whether hCG and IGFBP-1 appear in the same or different cells and in what sequence. DESIGN: Retrospective analysis of laboratory data. SETTING: University medical center. PATIENT(S): Twenty-five women undergoing IVF-ET with natural cycles and 25 women having stimulated IVF-ET. INTERVENTION(S): Cells were obtained from dominant follicles in women with natural cycles and from the follicles from hMG- and hCG-stimulated cycles. MAIN OUTCOME MEASURE(S): Detection and localization of hCG and IGFBP-1 in granulosa-luteal cells using double immunocytochemical staining. Measurement of hCG and IGFBP-1 in follicular fluid and serum. RESULT(S): Three types of hCG staining were found: on the cell surface, on the cell surface and in the cytoplasm, and in the cytoplasm alone. IGFBP-1 stained diffusely in the cytoplasm and was found only in those cells that were luteinized and contained hCG. IGFBP-1 and hCG were colocalized in the same cells. There was a positive correlation between follicular fluid hCG and IGFBP-1 levels, but only in natural IVF-ET cycles. CONCLUSION(S): HCG-driven luteinization is required for IGFBP-1 synthesis to take place in granulosa cells.     

Premature luteinization during gonadotropin-releasing hormone antagonist cycles and its relationship with in vitro fertilization outcome

OBJECTIVE: To determine the prevalence and the effect of premature luteinization in GnRH antagonist IVF-ET cycles. DESIGN: Prospective observational study. SETTING: In vitro fertilization-embryo transfer (IVF-ET) program at the Instituto Valenciano de Infertilidad. PATIENT(S): Eighty-one infertile patients undergoing controlled ovarian hyperstimulation with gonadotropins and GnRH antagonist for IVF-ET. INTERVENTION(S): Gonadotropin-releasing hormone (GnRH) antagonist was administered from stimulation day 6. Serum P, E(2), and LH were determined on the day of hCG administration. MAIN OUTCOME MEASURE(S): Cycles were grouped according to serum P level on the day of hCG administration (<1.2 ng/mL or > or =1.2 ng/mL). Clinical pregnancy and implantation rates were determined. RESULT(S): The incidence of premature luteinization was 38.3%. Total recombinant FSH dose and stimulation days differed significantly between the groups. Pregnancy rate (25.8% vs. 54.0%) and implantation rate (13.8% vs. 32.0%) were significantly lower in the premature luteinization group. CONCLUSION(S): Premature luteinization during GnRH antagonist IVF-ET cycles is a frequent event that is associated with lower pregnancy and implantation rates. Progesterone elevations are not related to serum LH levels and may reflect the mature granulosa cell response to high FSH exposure.     

来曲唑/FSH促排卵中GnRHa与hCG诱发卵泡成熟效果的比较

目的:比较曲普瑞林和hCG在来曲唑(LE)/FSH促排卵行IVF-ET治疗中诱发卵泡成熟的效果。方法:391个IVF-ET治疗周期随机分成促性腺激素激动剂(GnRHa)组(n=267)和hCG组(n=124),所有患者均采用LE/FSH促排卵方案,当主导卵泡平均直径达18～20mm时,GnRHa组患者采用达菲林0.1mg诱导卵泡成熟,hCG组采用hCG10000IU诱导卵泡成熟,比较组间的获卵数、MII卵率、受精率、卵裂率、优胚率、临床妊娠率和中-重度卵巢过度刺激综合症(OHSS)发生率。同时比较两组患者诱导日(d0)、取卵日(d2)、胚胎移植前日(d4)和胚胎移植后第4日(d9)的血清E2、P、LH水平。结果:hCG组Gn使用总量、MII卵率、卵裂率、中-重度OHSS发生率显著高于GnRHa组(P<0.05)。Gn使用天数、获卵数、受精率、种植率、临床妊娠率、流产率组间无统计学差异(P>0.05)。GnRHa组d0LH、d2LH、d9LH水平显著高于hCG组(P<0.05),而d2P、d4E2、d4P、d4LH、d9E2、d9P水平显著低于hCG组(P<0.05)。结论:在LE/FSH促排卵方案中可以用GnRHa替代hCG诱导卵泡成熟,而不影响IVF结局,并显著降低OHSS发生率。GnRHa诱导卵泡成熟的IVF周期其黄体期存在黄体功能不全,需适当补充外源性hCG加强黄体支持。     

A case of forearm amputation after ovarian stimulation for in vitro fertilization-embryo transfer.

OBJECTIVE: To report a case of forearm amputation after ovarian stimulation for IVF-ET. DESIGN: Case report. SETTING: A university hospital. PATIENT(S): A 41-year-old woman, who had coagulation disorder as a result of an ovarian hyperstimulation syndrome (OHSS) for IVF-ET. INTERVENTION(S): Retrospective evaluation of angiographic studies and surgical treatment. MAIN OUTCOME MEASURE(S): Medical follow-up after forearm amputation due to OHSS. RESULT(S): The patient underwent many cycles of IVF-ET with administration of purified FSH (75 IU 10 times per day, for 12 days) and chorionic gonadotropin (5,000 IU). The patient had a coagulation disorder as a result of OHSS, with thrombosis of the axillary vein, recurring after thromboarterectomy and leading to the paradoxical result of the amputation of an arm. CONCLUSION(S): An ethical evaluation of this case is mandatory, since the desire for pregnancy, the role of medical science, health, and human life itself are all factors involved.     

Mouse embryo culture as quality control for human in vitro fertilization: the one-cell versus the two-cell model

Female mice were superovulated with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) and mated with male mice. One-cell (n = 429) and 2-cell (n = 450) embryos were collected 20 and 42 hours after hCG and cultured in Ham's F-10 medium (Gibco, Grand Island, NY) (282 mOsm/l, pH 7.4) and in media of altered osmolality (260, 300, 316 mOsm/l), altered pH (7.0, 7.8, 8.0) or various dilutions of Cidex (Surgikos, Arlington, TX) (1:1000, 1:10,000, 1:100,000). Stages of development were observed for 4 days. The development of embryos in the 1-cell system was significantly impaired under all studied conditions by the 4-cell stage of development. The 2-cell system failed to detect trace amounts of Cidex in the culture media and an increase in osmolality to 300 mOsm/l. Other changes in osmolality (260 mOsm/l) and pH (7.8) were detected by the 2-cell system only at the blastocyst stage. The authors conclude that the 1-cell system is more sensitive than the 2-cell system to mild changes in in vitro fertilization culture media.     

Serum oxytocin profiles in patients with repeated implantation failure during IVF cycles

Abstract

Objective: The objective of this study is to investigate the association between oxytocin (OT) levels and repeated implantation failure (RIF) during in vitro fertilization-embryo transfer (IVF-ET) cycles.

Methods: Blood samples were collected from 108 women undergoing IVF-ET treatment at the following time points: gonadotrophin (Gn) administration day (Gn Day 0), hCG administration day (hCG Day 0), ET administration day (ET Day 0), and 5?d after ET (ET Day 5). Serum OT and steroid profiles were measured and compared among three groups: Group A included 38 women with a history of RIF, Group B included 41 women who became pregnant following the first fresh ET, and Group C included 29 women who did not become pregnant following the first fresh ET.

Results: The OT levels of the three groups at different time points were not significantly different. Serum OT levels were significantly higher on hCG Day 0, ET Day 0, and ET Day 5 than on Gn Day 0, and they were significantly correlated with the estradiol concentration on ET Day 0.

Conclusions: RIF patients do not have elevated serum OT levels during IVF-ET cycles.     

The effects of bromocriptine on VEGF,kidney function and ovarian hyperstimulation syndrome in in vitro fertilization patients: a pilot study

The aim of this study was to evaluate the effects of bromocriptine on vascular endothelial growth factor (VEGF) levels in serum, kidney function and ovarian hyperstimulation syndrome in women undergoing in vitro fertilization. Twenty-eight women were randomly divided into two groups and were administered daily oral capsules for 14 days, starting on the day of human chorionic gonadotropin (hCG) administration. Group A received 2.0?mg of folic acid, whereas Group B was given 2.5?mg of bromocriptine. Physical exams, pelvic ultrasounds and laboratory evaluations were performed on the day of hCG administration and again 7 days later. No differences in ovarian hyperstimulation syndrome, urine volume, creatinine clearance, urine sodium concentration or serum VEGF levels were found between the two groups. Thus, these results indicate that bromocriptine does not affect blood levels of VEGF, kidney function or the incidence of ovarian hyperstimulation syndrome in high-risk patients subjected to in vitro fertilization.     

超排卵周期卵巢反应性与体外受精、卵胞浆内单精子注射结局的关系

目的　探讨超排卵周期中卵巢反应性与体外受精 (IVF)、卵胞浆内单精子注射 (ICSI)结局的关系。方法　回顾分析 1999年 3月至 2 0 0 0年 12月间 ,4 74对不孕夫妇在本中心按常规方法行IVF 胚胎移植 (ET)及ICSI治疗的 5 10个周期。采用促性腺激素释放激素激动剂 (GnRH a) 高纯促卵泡激素 (FSH HP) 人绒毛膜促性腺激素 (hCG)长、短方案促排卵 ,以注射hCG日血清雌二醇 (E2 ) >110 10pmol L(16 0个周期 )为A组 ,获卵数 >15个 (14 8个周期 )为B组 ,A、B两组为卵巢高反应组 ;E2≤ 110 10pmol L(35 0个周期 )为C组 ,获卵数≤ 15个 (36 2个周期 )为D组 ,C、D两组为正常反应组。结果　高反应组与低反应组间 ,年龄、不孕时间、基础FSH水平及FSH用量差异有显著性 (P <0 0 1,P <0 0 5 )。A组着床率、妊娠率分别为 18 9% (94 4 98)与 38 8% (6 2 16 0 ) ,C组分别为 2 0 7% (2 12 10 2 6 )与4 1 4 % (14 5 35 0 ) ,两组比较 ,差异无显著性 (P >0 0 5 ) ;B组分别为 2 2 5 % (10 3 4 5 7)与 4 6 6 % (6 9 14 8) ,D组分别为 19 0 % (2 0 3 10 6 7)与 38 1% (138 36 2 ) ,两组比较 ,差异无显著性 (P >0 0 5 )。卵巢过度刺激综合征 (OHSS)发生率 ,A组为 6 9% (11 16 0 ) ,C组为 2 6 % (9 35 0 ) ,B组为 8 1% (     

A unique hypertonic response to hypotonic infusion in the pregnant ewe.

OBJECTIVE: The purpose of this study was to compare the responses of the maternal ewe to intravenous volume expansion with either sufficient lactated Ringer's solution to elevate maternal venous pressure or sufficient hypotonic fluid to reduce blood osmolality. STUDY DESIGN: Chronically catheterized pregnant sheep were intravenously infused over 4 hours with either commercial lactated Ringer's solution (5.55 +/- 0.50 L/hr, 255 mOsm/kg, mildly hypotonic) or diluted Ringer's solution (2.04 +/- 0.27 L/hr, 150 mOsm/kg, markedly hypotonic). Data were statistically analyzed with two- and three-factor analyses of variance and bivariate regression analysis. RESULTS: During the mildly hypotonic infusion (n = 8) the maternal blood osmolality changes were -5.1 +/- 1.2, +2.7 +/- 1.0 and +6.8 +/- 1.1 mOsm/kg at 1 and 4 hours of infusion and 1 hour after the infusion. In four of the eight animals in this group profuse diarrhea developed. During the markedly hypotonic infusion (n = 11) the maternal blood osmolality changes were -9.9 +/- 1.1, -15.9 +/- 2.5, and -10.4 +/- 2.2 mOsm/kg at 1 and 4 hours of infusion and 1 hour after the infusion. Although urine osmolalities were significantly less than the osmolality of the infusate in both groups, only during the mildly hypotonic infusion was there a net loss of free water by the kidneys. The renal free water loss, the venous pressure increase, and the blood osmolality decrease were not significantly different whether diarrhea did or did not develop. CONCLUSION: The infusion of large volumes of mildly hypotonic Ringer's solution to the pregnant ewe produces a paradoxic increase in maternal plasma osmolality as a result of the excretion of large volumes of free water by the kidneys, and if the venous pressure is increased more than about 6 mm Hg with this infusion, diarrhea develops in the animals.     

Pyridostigmine cotreatment for controlled ovarian hyperstimulation in low responders undergoing in vitro fertilization-embryo transfer

OBJECTIVE: To investigate the effect of pyridostigmine, an acetylcholinesterase inhibitor, as cotreatment for controlled ovarian hyperstimulation (COH) in low responders. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: A reproductive medicine unit in a university hospital. PATIENT(S): Seventy infertile women with a history of low ovarian response to COH using a GnRH agonist as part of a long stimulation protocol in previous IVF-ET cycles. INTERVENTION(S): Sixty milligrams of pyridostigmine or placebo was administered orally twice daily from the first day of COH until the day of hCG injection in patients undergoing IVF-ET cycles. MAIN OUTCOME MEASURE(S): In vitro fertilization results, pregnancy outcome, and serum and intrafollicular concentrations of GH and insulin-like growth factor-1. RESULT(S): Pyridostigmine cotreatment was associated with significant decreases in the amount of gonadotropins and the duration of stimulation required. The clinical pregnancy rate was higher in the pyridostigmine group, but this difference was not statistically significant (25.7% vs. 11.4%). The serum GH level on the day of hCG injection was significantly higher in the pyridostigmine group than in the placebo group. Follicular fluid concentrations of GH and insulin-like growth factor-1 were significantly higher in the pyridostigmine group. CONCLUSION(S): This study suggests that pyridostigmine cotreatment for COH could affect the serum and intrafollicular GH and insulin-like growth factor-1 concentrations and, hence, improve the ovarian response to COH and the results of IVF in low responders undergoing IVF-ET.     

Role of three-dimensional ultrasonographic measurement of endometrium volume as a predictor of pregnancy outcome in an IVF-ET program: a preliminary study

OBJECTIVE: To evaluate the role of three-dimensional (3D) ultrasonographic measurement of the endometrium in predicting pregnancy in an IVF-ET program. DESIGN: Prospective study. SETTING: Center for assisted reproductive techniques. PATIENT(S): 65 women undergoing controlled ovarian hyperstimulation for IVF. INTERVENTION(S): Ultrasonographic examination on the day of hCG administration. MAIN OUTCOME MEASURE(S): Endometrial volume, endometrial thickness, and pregnancy rate. RESULT(S): The mean (+/-SD) endometrium volume (4.16 +/- 1.97 mL), endometrium thickness (11 +/- 2 mm), and estradiol level (1686.82 +/- 1057.10 pg/mL) in 21 pregnant women on the day of hCG administration did not differ statistically differ from the respective values in 44 nonpregnant women (4.53 +/- 1.79 mL; 11 +/- 2 mm, 1883.56 +/- 1147.21 pg/mL). Receiver-operating characteristic curves showed that the area under curve (AUC) was 0.57 for endometrial volume and 0.48 for endometrial thickness. Using a cut-off value of 2.5 mL for endometrial volume to predict pregnancy, results of the Fisher exact test were statistically significant. No significant cut-off value was found for endometrial thickness. CONCLUSION(S): Endometrial volume and thickness on the day of hCG administration did not predict occurrence of pregnancy. A minimum volume of 2.5 mL appeared to favor pregnancy. The predictive value of 3D ultrasonographic measurement of endometrial volume and thickness was better than that of 2D measurement.     

Vascular endothelial growth factor, interleukin-6 and interleukin-2 in serum and follicular fluid of patients with ovarian hyperstimulation syndrome

BACKGROUND: The pathogenesis of ovarian hyperstimulation syndrome (OHSS) is not completely understood. OBJECTIVE: To investigate the presence of VEGF, IL-6 and IL-2, in serum and follicular fluid, in patients developing severe OHSS. STUDY DESIGN: We enrolled 101 women undergoing in vitro fertilization. Eight patients developing severe OHSS were compared with 43 high risk patients and 50 controls. We analyzed VEGF and IL-6 in serum collected before hCG administration, and in both serum and follicular fluid on the day of oocyte retrieval. RESULTS: OHSS patients presented follicular fluid IL-6 levels higher than both the patients at risk and controls (P<0.05). On the day of the oocyte retrieval the patients developing OHSS showed serum and follicular VEGF values higher than the ones of the patients at risk (P<0.05). Serum and follicular fluid IL-2 levels showed no differences between the examined groups. IL-2, IL-6 and VEGF values were not correlated with each other. CONCLUSIONS: Angiogenesis and inflammation processes are both present in severe OHSS.