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PubMed2004

First successful case of in vitro fertilization-embryo transfer with venom immunotherapy for hymenoptera sting allergy.

BACKGROUND: To describe immune and endocrine responses in severe hymenoptera hypersensitivity requiring venom immunotherapy (VIT) during in vitro fertilization (IVF). CASE PRESENTATION: A 39-year old patient was referred for history of multiple miscarriage and a history of insect sting allergy. Four years earlier, she began subcutaneous injection of 100 mcg mixed vespid hymenoptera venom/venom protein every 5-6 weeks. The patient had one livebirth and three first trimester miscarriages. Allergy treatment was maintained for all pregnancies ending in miscarriage, although allergy therapy was discontinued for the pregnancy that resulted in delivery. At our institution ovulation induction incorporated venom immunotherapy (VIT) during IVF, with a reduced VIT dose when pregnancy was first identified. Serum IgE was monitored with estradiol during ovulation induction and early pregnancy. Response to controlled ovarian hyperstimulation was favorable while VIT was continued, with retrieval of 12 oocytes. Serum RAST (yellow jacket) IgE levels fluctuated in a nonlinear fashion (range 36-54%) during gonadotropin therapy and declined after hCG administration. A healthy female infant was delivered at 35 weeks gestation. The patient experienced no untoward effects from any medications during therapy. CONCLUSION: Our case confirms the safety of VIT in pregnancy, and demonstrates RAST IgE can remain <60% during IVF. With proper monitoring, VIT during IVF can be safe and appropriate for selected patients and does not appear to adversely affect blastocyst implantation, early embryo development or perinatal outcome. Further studies will be needed to develop VIT guidelines specifically applicable to IVF.

Journal Article↗
PubMed1998

Fertility in anovulatory patients after primary cesarean section.

OBJECTIVE: To evaluate the fertility potential after primary cesarean section (CS) in anovulatory patients treated for ovulation induction with gonadotropins. STUDY DESIGN: A controlled, prospective study was conducted on 97 anovulatory patients who delivered a neonate either abdominally or vaginally after ovulation induction with human menopausal gonadotropin/human chorionic gonadotropin (hMG/hCG). After four cycles of hMG/hCG therapy, cumulative pregnancy rates and abortions were observed. In both groups, patients who did not conceive underwent hysterosalpingography to evaluate uterine and tubal patency. RESULTS: The cumulative pregnancy rate in the anovulatory, post-cesarean section patients treated with hMG/hCG was 61.9%, as compared to 59.6% in the control group (statistically nonsignificant). The abortion rate was similar in both groups. CONCLUSION: The risk of uterine or tubal infertility is probably not substantially increased in patients on whom uncomplicated cesarean sections have been performed. Anovulatory patients who conceive after treatment with gonadotropins and deliver abdominally should be referred for medical treatment before evaluation of any uterine or tubal infertility.

Adult↗
PubMed1996

Intrafollicular insulin-like growth factor-II levels in normally ovulating women and in patients with polycystic ovary syndrome.

OBJECTIVE: To investigate intrafollicular insulin-like growth factor II (IGF-II) in patients affected with polycystic ovary syndrome (PCOS) in comparison with normal women. DESIGN: Insulin-like growth factor-II was determined in 103 follicular fluids (FF) from normally ovulating women and in 102 FF from patients with PCOS. Ribonucleic acid was extracted from granulosa cells of follicles obtained from control and PCOS patients and from tissue from polycystic ovaries. SETTING: Procedures were performed in a university laboratory. PATIENTS: Twenty-nine normally ovulating women and 19 patients with PCOS underwent ovulation induction for IVF-ET with LH-releasing hormone (LH-RH) analog and gonadotropins. Eleven of them, 4 to 8 months later, underwent ovulation induction with approximately the same dosage of gonadotropins plus a standard dosage of GH. MAIN OUTCOME MEASURES: Intrafollicular IGF-II, IGF-I, epidermal growth factor (EGF), transforming growth factor beta 2, (TGF-beta 2), inhibin, and steroids were evaluated by appropriate RIA, immunoenzymatic assay (EIA), and ELISA assays. The expression of the gene encoding IGF-II was analyzed by Northern blot. RESULTS: Intrafollicular IGF-II was lower in PCOS than in controls. Accordingly, IGF-II messenger RNA expression was lower in PCO than in normal granulosa cells. Several differences in FF IGF-I, EGF, inhibin, and TGF-beta 2 concentrations were observed between PCOS and controls. CONCLUSIONS: Both IGF-II and IGF-I were reduced in PCOS, confirming a possible role of an IGF imbalance in the development of this disease.

Adult↗
PubMed1995

Comparison between nafarelin acetate and D-Trp6-LHRH for temporary pituitary suppression in in vitro fertilization (IVF) patients: a prospective crossover study.

PURPOSE: Nafarelin acetate is a new gonadotropin releasing (GnRH) agonist analogue with unique potency, intranasal administration, and convenient storage. Hence, nafarelin was considered as an alternative for temporary pituitary suppression in patients undergoing ovulation induction in IVF. A crossover treatment in a prospective study was performed including 40 women with bilateral obstructed tubes and normal ovarian function, treated in 80 ovulation induction cycles using the long protocol. Twenty patients used nafarelin acetate 600 micrograms/daily in their first cycle and received D-Trp6-LHRH, 0.5 mg/daily, in their following cycle. The other 20 women used decapeptyl in their cycle and received nafarelin in the second. RESULTS: Estradiol suppression was achieved by both D-Trp6-LHRH and nafarelin at equal time intervals. The average total number of ampoules (P = 0.0005) and the length of administration of hMG required for ovarian stimulation (P = 0.0002) and the time interval between GnRHa initiation to oocyte retrieval (P = 0.04) was significantly lower in nafarelin cycles. The number and the distribution between large and small follicles as well as the average number of oocytes retrieved did not differ between the two GnRH analogues. CONCLUSION: Our results demonstrate that nafarelin acetate is comparable to D-Trp6-LHRH for temporary pituitary suppression used for controlled ovarian stimulation in IVF patients. However, using nafarelin ovarian stimulation was achieved with few ampoules of hMG, administered for a shorter period of time, thus with a lesser cost.

Adult↗
PubMed2006

Clomiphene citrate challenge test predicts outcome of intrauterine insemination in women aged under 37 years.

The clomiphene citrate challenge test is a tool to predict ovarian reserve and fertility. It has mainly been used as a predictor of success of IVF/intracytoplasmic sperm injection (ICSI) cycles. Infertile young women with diminished ovarian reserve have a worse prognosis than women with adequate ovarian reserve attempting IVF/ICSI cycles. Nothing is known regarding the outcome of young women with diminished ovarian reserve undergoing low-complexity assisted reproductive treatment such as ovulation induction plus intrauterine insemination (IUI). This study included all women under 37 years who consulted in the authors' centre between May 2004 and August 2005 who underwent ovulation induction and IUI. Ninety-six women younger than 37 years with adequate ovarian reserve, and 50 women with diminished ovarian reserve were found. The pregnancy rate and pregnancy rate per cycle in the adequate ovarian reserve group were significantly higher than those of the diminished ovarian reserve group (46.7% versus 25%, P < 0.02 ; 15.9% versus 7.6%, P < 0.02 respectively). It is concluded that the clomiphene citrate challenge test is a good predictor of low-complexity infertility intervention outcome, and represents an effective tool to establish a prognosis. Therefore, it is very useful in planning therapy, and advising the infertile couple.

Adult↗
PubMed2000

The role of inhibin in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common heterogeneous disorder which, in its severest manifestations, is associated with anovulation, hyperandrogenism and metabolic imbalance. The biochemical markers for the condition can include a significantly raised LH:FSH ratio and a raised testosterone concentration, indicating a derangement of the hypothalamo--pituitary--ovarian axis which may be primary or secondary to a primary ovarian pathology. The bioactive inhibins are heterodimeric glycoproteins consisting of alpha-betaA (inhibin A) and alpha-betaB (inhibin B) subunits. They play an endocrine role in co-regulating (with oestradiol) the suppression of FSH during the late follicular and luteal phases of the ovarian cycle and they are implicated in intraovarian paracrine signalling. Inhibin B, which is the predominant form in small pre-ovulatory follicles, increases in concentration from early in the follicular phase to reach a peak coincident with the onset of the decrease in FSH which forms the basis of the pattern of mono-ovulation seen in normo-ovulatory women. Several unique features of the dysovulation of women with PCOS, namely their failure to recruit and develop a dominant follicle despite having 'normal' concentrations of endogenous FHS, the raised LH:FSH ratio and their exquisite sensitivity to exogenous FSH injections, may be explained by their significantly higher inhibin B concentrations. Studies into inhibin B parameters in women with PCOS demonstrate that women with anovular PCOS have significantly higher concentrations of circulating inhibin B and that they lack the pulsatile pattern of secretion that can be detected in normo-ovulatory women during the mid-follicular phase. The inhibin B response to ovulation induction with clomiphene citrate in women with PCOS differs from that in normo-ovulatory women taking the antioestrogen. Women with PCOS who over-respond to ovulation induction with injected FSH in a 'low-dose' step-up protocol' and recruit multiple follicles have significantly higher concentrations of pre-treatment inhibin B than PCOS subjects who do not.

Journal Article↗
PubMed2005

Embryonic loss in iatrogenic multiples.

Spontaneous reduction of multiple gestational sacs occurs less often in pregnancies conceived as a result of ovulation induction and assisted reproductive technology compared with spontaneously conceived multiple pregnancies. Whereas most spontaneous multiple pregnancies are twin gestations, a higher proportion of multiple pregnancies that result from ovulation induction and assisted reproductive technology are triplet and higher-order gestations. Recent evidence, described in this article, indicates that although twin and higher-order multiple gestations found on initial ultrasound subsequently may undergo spontaneous reduction to singletons or twins, there may be important consequences for the outcome of the surviving fetus or fetuses.

Birth Weight↗
PubMed1995

Timing of hCG administration in cycles stimulated for in vitro fertilization: specific impact of heterogeneous follicle sizes and steroid concentrations in plasma and follicle fluid on decision procedures.

The timing of ovulation induction is usually decided according to estradiol plasma concentrations and follicle size. We administered human chorionic gonadotropin (hCG) when at least three follicles of 16 mm or more in diameter and adequate estradiol plasma concentrations were detected. We studied the percentage of mature oocyte-cumulus-corona radiata complexes, estradiol and progesterone concentrations in a heterogeneous sized follicle population (range 10-20 mm, n = 90) to perform a retrospective analysis of the adequacy of criteria adopted for the timing of ovulation induction. Plasma and follicular fluid were obtained from 20 normo-ovulating women (aged 28-37 years) treated with gonadotropin releasing hormone analogs (GnRH-a) and human menopausal gonadotropin (hMG) for in vitro fertilization (IVF). No correlation was found between the mean individual follicular fluid estradiol concentration (500-5640 nmol/l) and the respective maximum concentration in plasma (2-16 nmol/l). The estradiol concentration was similar in all follicles. Total follicular fluid estradiol concentration was found to be correlated with follicular fluid volume (r = 0.771, p < 0.01). On the day of hCG administration, the concentration of estradiol in the plasma but not the follicular fluid was correlated with the number of oocyte-cumulus-corona radiata complexes collected (p < 0.01) and the number of mature complexes (p < 0.01). At oocyte pick-up, the plasma concentration of progesterone was correlated (p < 0.01) with number of complexes collected and the number of mature complexes. The percentage of mature complexes collected (77.5%) was higher than suggested by the number of leading follicles. This indicates that our criteria for administering hCG were adequate and that heterogeneous follicle size does not exclude a high rate of mature oocyte-cumulus-corona radiata complexes.

Adult↗
PubMedDate not supplied

Growth hormone--non multum sed multa (quality, not quantity).

In view of the recent availability of recombinant human growth hormone (GH) and reports of its ability to augment ovulation induction by exogenous gonadotropins, we have surveyed the reproductive physiological role of GH and the family of polypeptides that mediate its action. The clinical studies using GH to improve ovulation induction, although achieving a significant reduction in exogenous gonadotropin administration, show only minor benefits in terms of attainment of pregnancy. An explanation for this phenomenon is suggested, and we provide guidelines for whom GH should be recommended.

Animals↗
PubMedDate not supplied

[Results of intrauterine insemination after induction of multiple follicular growth].

The authors used multiple ovulation induction by CC+hMG+hCG and intrauterine insemination with capacitized sperm in 63 women, aged between 22 and 43 (mean age 32.474 +/- 5.364) with primary or secondary infertility of various origins (tubal problems being excluded) to enhance the chances of pregnancy and evaluate the pregnancy rate. Partners were aged between 26 and 47 (mean age 36.571 +/- 6.709). The following parameters were considered in all patients: mean age of the partners of the couple, parity, seminal fluid characteristics, duration of infertility, dose of each drug administered, mean number of ampuls per patient and mean 17 beta-estradiol level at the time of administration of hCG. There were 189 cycles induced and 26 suspended (13.75%) including 7 (3.70%) because of protocol drop-out, 13 (6.87%) because of the development of slight hyperstimulation and 6 (3.17%) because of marked hyperstimulation. There were 27 pregnancies (42.85%), 4 of which ended in miscarriage between 7 and 10 weeks. There were 4 twin pregnancies, i.e. 14.81%. Of the 27 pregnancies, 13 (48.14%) were obtained during the first cycle, 9 (33.33%) during the second cycle and 5 (18.51%) during the 3rd cycle. The rate of pregnancies per cycle was 14.89%. With regard to 17 beta-estradiol levels at the time of administration of hCG, 18 pregnancies (69.23%) were obtained in patients with a 17 beta-estradiol level > or = to 1300, 7 (25.92%) in patients with a 17 beta-estradiol level > or = to 1000 and < or = to 1300 pg/ml and 3 (11.11%) in those with a 17 beta-estradiol level < or = to 900 pg/ml.

Adult↗
PubMed1992

Prospective study of short and long regimens of gonadotropin-releasing hormone agonist in in vitro fertilization program.

OBJECTIVE: To assess the usefulness of a short regimen in ovulation induction in an in vitro fertilization (IVF) program. DESIGN: A prospective randomized trial was set up to compare long and short regimens of gonadotropin-releasing hormone agonist administration for ovulation induction in IVF. SETTING: Aberdeen Assisted Reproduction Unit. PATIENTS: Eighty-seven patients undergoing IVF were randomized between the two protocols. Stimulation regimen was the only variable being tested. MAIN OUTCOME MEASURES: Stimulation response and occurrence of luteinizing hormone (LH) surges. RESULTS: There was no difference in the stimulation requirements, response to stimulation, number of follicles aspirated, or the number of oocytes obtained. The fertilization rates, number of embryos transferred, and pregnancy rates were also similar in both groups. Like the long regimen, it prevents the occurrence of a premature LH surge. CONCLUSION: The short regimen is a useful and cheaper alternative in ovarian stimulation of patients undergoing IVF.

Adult↗
PubMed1995

Normal development and metabolic activity of preimplantation embryos in vitro from patients with polycystic ovaries.

Polycystic ovary syndrome (PCOS) is closely associated with high miscarriage rates and, following in-vitro fertilization (IVF), with decreased fertilization rates, suggesting that oocytes and embryos are of poor quality. In this prospective study, we examined the development, metabolic activity and blastocyst cell number of embryos following IVF from 51 patients with either anovulatory PCOS, ovulatory PCOS or tubal disease. The number of oocytes retrieved and the fertilization rates were similar for patients with PCOS and tubal disease. Following embryo transfer, 46% of the patients with PCOS and 36% of patients with tubal disease became pregnant. A similar proportion of surplus embryos from patients with PCOS and tubal disease developed to the blastocyst stage (38% and 43% respectively). Patients with anovulatory PCOS had embryos with less fragmentation which cleaved faster, cavitated earlier and had more cells at the blastocyst stage than embryos from patients with tubal disease. While the profile of glucose uptake and lactate production was similar for all groups throughout preimplantation development, patients with tubal disease who underwent ovulation induction using the 'titrated' regimen optimized for PCOS patients resulted in embryos with reduced pyruvate uptake, in addition to low blastocyst cell numbers. This study demonstrates that with an optimized ovulation induction regimen, embryos from PCOS patients are of good quality and developmental potential.

Adult↗
PubMed2001

[Concentrations of MMP-1, TIMP-1, MMP-1/TIMP-1 and I CTP complexes in follicular fluid as related to fertilization rate in women treated with in-vitro fertilization].

OBJECTIVES: Metalloproteinases and their inhibitors appear to control connective tissue remodelling during follicular rupture. The aim of the study was to establish if oocytes fertilisation rate after ovulation induction depends on the concentrations of MMP-1, its inhibitor TIMP-1, MMP-1/TIMP-1 complex and I CTP in follicular fluid (FF). MATERIAL AND METHODS: FF were collected from 37 infertile patients undergoing ovulation induction using either short or long protocol. FF was obtained 36 hours after administration of hCG (Pregnyl). The level of MMP-1, TIMP-1, MMP-1/TIMP-1 complex were measured using ELISA kits and I CTP, E2, FSH, LH, using RIA assay kits. RESULTS: Statistically significant (p < 0.05) difference was found in TIMP-1, E2, and FSH concentration, being higher in the group with more than 75% fertilisation rate: TIMP-1 728.8 + 100.1 ng/ml vs 666.3 + 94.5 ng/ml; E2 477.3 +/- 160.0 ng/ml vs 368.0 +/- 190.0 ng/ml and FSH 7.27 +/- 1.45 mIU/ml vs 6.24 +/- 1.6 mIU/ml. CONCLUSIONS: Statistically significant increase in TIMP-1 concentration observed among patients with fertilisation rate above 75% indicates an important role of this substance in ovulation process.

Adult↗
PubMed1991

Treatment of anovulation due to polycystic ovarian syndrome by laparoscopic ovarian electrocautery.

Our experience of ovarian electrocautery for the treatment of polycystic ovarian syndrome (PCOS) in ten women is described. We found that nine responded favourably, either ovulating spontaneously or becoming more responsive to ovulation induction. There was a significant and persistent fall in serum testosterone levels, and a transient fall with subsequent rise in inhibin. We recommend that laparoscopic ovarian electrocautery is considered as an alternative to ovulation induction with gonadotrophins, in women with PCOS who fail to respond to clomiphene citrate.

Adult↗
PubMed1992

Oogenesis, fertilisation and early embryonic development in rats. II: Dose-dependent effects of human chorionic gonadotrophin.

A total of 950 female Wistar rats in 81 groups were involved in this study. Different groups of rats were stimulated with PMSG (0, 10 & 20 IU) at diestrus followed, 48-52 hr later, by different doses of HCG (0, 10, 20, 30 & 40) for ovulation induction. The dose-dependent effects of HCG, either with or without the use of PMSG for stimulation of multiple follicular development, on the quality of oocytes and their in vitro fertilisability, quality of Day 2-embryos, viability of pregnancy and status of embryos retrieved on Day 2, 3, 4 or 5 of pregnancy in different subgroups of rats were examined. Results showed that more oocytes and embryos fertilised in vivo were retrieved from rats supraphysiologically stimulated with 20 IU of PMSG. The addition of HCG did not increase the number of ovulated oocytes or Day-2 embryos. In other words, the number of oocytes or embryos produced is dependent on the dose of PMSG administered during diestrus rather than on the dose of HCG given for ovulation induction. Hence, no increase in the amount of HCG is required to effectively ovulate bigger cohort of preovulatory follicles in supraphysiologically stimulated rats. As was shown earlier, in vitro and in vivo fertilisation rates were reduced when higher doses of PMSG were used. Similarly, these rates were reduced when increasing doses of HCG were used in rats not previously stimulated with PMSG. When higher doses of HCG were used in rats stimulated earlier with PMSG (10 and 20 IU), the in vitro but not the in vivo fertilisation rates were further reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2001

Effect of gonadotrophin dose on oocyte retrieval in superovulated BALB/c mice.

Mice are commonly used animal models in reproductive and developmental research. In order to get satisfying results from such experiments, large numbers of ova must be available and this can be achieved by using various ovulation induction protocols. To obtain an optimal response from these stimulation protocols, parameters such as breeding-housing conditions of the animal strains, the best age for superovulation, and type and dose of gonadotrophins must be optimized. The aim of this study was to investigate the impact of exogenous stimulation with increasing amounts of gonadotrophins on the number and quality of oocytes/pre-embryos recovered from outbred BALB/c mice. A dose-response analysis was performed by stimulating prepubescent (21- to 25-day-old) and sexually mature (6 to 8 weeks old) female mice with hMG, which contains equal amounts of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The stimulation dose contained 5, 10, 15, 20, 25 or 30 IU of FSH/LH. The effect of increasing stimulation was assessed by monitoring the number and maturity of ova recovered from the tubes. The data were analyzed by using a one-way Anova test and student t-test. Increasing stimulation doses in the prepubescent females resulted in an increased number of ova. A maximum of 55 ova per mouse was reached when stimulating with 20 IU of FSH/LH; higher stimulation doses showed no further increase in oocyte recovery. In the prepubescent group, a maximal number of recovered mature ova was reached with 15 IU of FSH/LH. In the sexually mature female group, 20 IU of FSH/LH gave the best quantitative and qualitative results. Positive effects of copulation on the number and maturity of oocytes in all induction doses were more evident in the prepubescent females and these parameters were significantly more improved (P < 0.05) in this group when compared to the pubertal females. Our findings led to the conclusion that ovulation induction of prepubescent outbred BALB/c mice with 15 IU FSH/LH and sexually mature ones with 20 IU FSH/LH give the best results in terms of oocyte number and maturity.

Animals↗
PubMed1997

Long-term administration of pulsatile gonadotropin-releasing hormone for exploration of pituitary functionality in amenorrheic patients.

Differentiation between hypothalamic and pituitary amenorrhea is generally based on the luteinizing hormone-releasing hormone (LHRH) test (whether as a single dose, two consecutive doses, or pulsatile over 5-10 days), together with high-resolution imaging (computed tomography or magnetic resonance) of the sellar region. Long-term administration of gonadotropin-releasing hormone (GnRH) is generally used only for ovulation induction, and not for diagnostic purposes. Here, we report the results of long-term administration of GnRH to 19 women initially diagnosed as suffering from hypothalamic amenorrhea on the basis of LHRH testing and computed tomography imaging. During treatment, subjects received 20-micrograms pulses of GnRH every 90 min, subcutaneously from a portable infusion pump. Fourteen subjects responded (i.e. ovulated) during the first treatment cycle; one subject menstruated but did not ovulate during the first cycle, and the dropped out of the study; the remaining four subjects did not ovulate or menstruate despite at least three treatment cycles. Magnetic resonance imaging of the sellar region of these four subjects revealed pituitary lesions (partially empty sella in three cases, microadenoma in one case) which had not been detected by computed tomography. By contrast, no such abnormalities were detected in the nine responders who agreed to undergo magnetic resonance imaging. These findings suggest that long-term administration of GnRH is of value not only for ovulation induction but also for diagnostic purposes. Specifically, an initial diagnosis of hypothalamic amenorrhea is confirmed if there is a positive ovulation response after two GnRH treatment cycles; otherwise, pituitary amenorrhea should be suspected. Our results also suggest that magnetic resonance imaging is more effective than computed tomography for the detection of partially empty sella.

Adult↗