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PubMed1992

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

OBJECTIVE: To assess the usefulness of the ultrashort regimen of gonadotropin-releasing hormone agonist (GnRH-a) in ovulation induction in an in vitro fertilization (IVF) program. DESIGN: A prospective randomized trial comparing short and ultrashort regimens of GnRH-a. SETTING: Aberdeen Assisted Reproduction Unit. PATIENTS: Forty-eight patients having IVF for the first time were randomized between the two protocols. MAIN OUTCOME MEASURES: Response to ovarian stimulation and occurrence of spontaneous luteinizing hormone (LH) surges. RESULTS: In ovulation induction, fertilization, and pregnancy rates the ultrashort regimen produces results that were no different to the short regimen but it did not always prevent an LH surge. CONCLUSION: The ultrashort regimen can be a useful alternative for ovarian stimulation of patients undergoing IVF.

Adult↗
PubMed2006

Quality of life of patients undergoing ovarian stimulation with injectable drugs in relation to medical practice in France.

The French study VISION is a multicentric, prospective and retrospective study, designed first to evaluate patients' quality of life during ovarian stimulation for ovulation induction, intrauterine insemination (IUI) or IVF, and secondly to analyse current medical practice in France. Answers were directly entered on a pocket PC. The study was conducted from January to August 2004 and 186 practitioners filled in a total of 1476 questionnaires. The percentages for the different treatments used were analysed according to type of technique [ovulation induction, IUI, IVF/intracytoplasmic sperm injection (ICSI)], type of product used [urinary gonadotrophins, recombinant FSH (rFSH), gonadotrophin-releasing hormone (GnRH) agonists and antagonists] and methods of administration (intramuscularly, subcutaneously, use of Pen-injector, nurses or self-injections). Initial and total amounts of urinary gonadotrophins per cycle were approximately 30% higher compared with rFSH for IUI and IVF. Generally, the impact of these treatments on professional or social life was less than expected. Patients saw self-injection as a significant improvement in their life, especially when using an injection pen, and when other drugs were also self-injected during treatment (human chorionic gonadotrophin, GnRH agonists or antagonists). Clear information is necessary to increase patient's compliance to the treatment. Simplification will make these procedures more patient-friendly and less of a struggle.

Activities of Daily Living↗
PubMed2001

Basal and day 12 inhibin concentrations in the prediction of ovarian response to gonadotrophins in women with PCOS.

BACKGROUND: In this study, we aimed to investigate whether basal and day 12 serum total inhibin concentrations in women with polycystic ovarian syndrome (PCOS) were of predictive value for the estimation of the ovarian response to gonadotrophins. METHODS: Ovulation induction with a very low dose gonadotrophin protocol, starting with 37.5 IU/day, was performed for 40 cycles on 35 patients with PCOS. Day 3 (basal) serum total inhibin, FSH and oestradiol concentrations; day 12 dominant follicle diameter, inhibin and oestradiol concentrations and midluteal serum progesterone concentrations were measured during the 40 cycles. The correlations between basal and day 12 inhibin concentrations and some critical ovulation monitoring parameters were investigated. RESULTS: Ovulation was obtained in 14 out of 40 cycles: 21% of cycles with basal inhibin <1.0 IU/ml; 33.3% of cycles with basal inhibin between 1.0-1.9 IU/ml; and 83.3% of those with inhibin concentrations > or =2 IU/ml were ovulatory (P < 0.05). Ovulation was achieved in 91.6% of the cycles with a day 12 inhibin concentration > or =4 IU/ml. CONCLUSIONS: Basal inhibin concentrations may determine poor and good responders to ovulation induction with very low dose gonadotrophin protocol in patients with PCOS. The day 12 inhibin concentration was found to be a more sensitive parameter than the oestradiol concentration in the prediction of follicular maturation.

Adult↗
PubMed1993

Evaluation of the significance of the estradiol response during the clomiphene citrate challenge test.

OBJECTIVE: To evaluate the relationship between the E2 response during the clomiphene citrate (CC) challenge test and ovarian responsiveness to exogenous gonadotropins. DESIGN: Performance of a CC challenge test followed by ovulation induction with exogenous gonadotropins as part of participation in an assisted reproduction program. SETTING: Assisted reproduction program in a large military tertiary care center. PATIENTS: Two hundred forty-seven women between the ages of 24 and 39 years with normal CC challenge tests within 1 year of their assisted reproduction cycle. INTERVENTIONS: Performance of CC challenge tests and ovulation induction with exogenous gonadotropins as a component of an assisted reproduction cycle. MAIN OUTCOME MEASURES: Correlation of the E2 response during the CC challenge test and peak E2, the duration of stimulation, number of ampules of exogenous gonadotropins, number of mature follicles, number of mature oocytes recovered, and fertilization and pregnancy rates in an assisted reproduction program. RESULTS: No correlation exists between the E2 response during the CC challenge test and any of the parameters evaluated. CONCLUSION: Monitoring of the E2 response during the CC challenge test did not predict ovarian responsiveness or pregnancy rates in patients participating in an assisted reproduction program and one may choose not to include it in routine testing.

Adult↗
PubMed2000

Usefulness of Doppler sonography in the diagnosis of ovarian torsion.

OBJECTIVE: To assess the predictive value of Doppler sonography in the diagnosis of ovarian torsion and to correlate Doppler results with surgical findings and various clinical characteristics. DESIGN: Retrospective study of discharged inpatients. SETTING: An academic community hospital. PATIENT(S): Twenty-one patients with surgically confirmed ovarian torsion over an 8-year period. INTERVENTION(S): Data were collected on Doppler flow results, ultrasound and surgical findings, patient characteristics, and associated morbidity. MAIN OUTCOME MEASURE(S): Accuracy of Doppler diagnosis as to presence of ovarian torsion. RESULT(S): Twenty-one patients had surgically confirmed ovarian torsion. Doppler sonography was performed in 10 of the 21 patients. Doppler sonographic findings were normal in 60% (6 of 10), and abnormal (decreased or absent) in 40% suggestive of torsion. In cases involving ovulation induction, Doppler sonography findings were normal in 25% (1 of 4). Furthermore, the time to diagnosis of ovarian torsion (mean = 5.3 hours) and the time to hospital discharge (mean = 2 days) were both decreased when compared with instances when normal flow was detected by Doppler sonography (59 hours and 2.7 days, respectively). CONCLUSION(S): Abnormal flow detected by Doppler sonography is highly predictive of adnexal torsion and is therefore useful in the diagnosis of ovarian torsion. However, when normal flow is detected by Doppler sonography, it does not necessarily exclude an ovarian torsion; in fact, torsion is missed in 60% of cases, and time to diagnosis in these cases is delayed. In cases of ovulation induction, sensitivity is increased to 75%.

Adult↗
PubMed2006

Pregnancy outcome among twins conceived after subfertility treatment compared with natural twins: A population-based study.

Pregnancy outcome and characteristics of women who conceive following subfertility treatment remains a subject of great interest. We analyzed these variables among 199 women who delivered a registerable twin birth compared with 1773 women who delivered a naturally conceived twin birth in a population-based obstetric cohort drawn from around Oxford, England. Treatment was restricted to conceptions involving simple ovulation induction only. Treated mothers were of significantly higher social class and older, more likely to deliver girls and to be delivered by cesarean section, and significantly less likely to be smokers at the time of antenatal booking and to have delivered previous pregnancies. Pregnancy outcome was similar between the two groups for most measures, with the exception of birthweight which was lower in treated twins, though not significantly so. Overall the results are reassuring with respect to outcome in twin pregnancies following simple ovulation induction.

Adult↗
PubMed2005

Metformin administration and laparoscopic ovarian drilling improve ovarian response to clomiphene citrate (CC) in oligo-anovulatory CC-resistant women with polycystic ovary syndrome.

OBJECTIVE: To compare the efficacy of clomiphene citrate (CC) administration for ovulation induction in CC-resistant oligo-ovulatory women with polycystic ovary syndrome (PCOS) after metformin treatment or laparoscopic ovarian drilling (LOD). Design Prospective controlled study. PATIENTS: Twenty-eight overweight oligo-amenorrhoeic women with PCOS who were still anovulatory after metformin administration (group A, n = 8) or LOD (group B, n = 20). METHODS: Treatment with CC 150 mg/day for 5 days from the third to the seventh day of a progesterone-induced uterine bleeding for 6 months. MEASUREMENTS: The ovulation, pregnancy, abortion and live-birth rates were evaluated in each group. RESULTS: The subjects of groups A and B were studied for a total of 36 and 74 cycles, respectively. At the end of the study, no differences in ovulation [11/36 (30.6%) vs. 23/74 (31.1%); P = 0.96], pregnancy [6/36 (16.7%) vs. 12/74 (16.2%); P = 0.95], abortion [2/6 (33.3%) vs. 5/12 (41.7%); P = 1.00] and the live-birth [4/6 (66.7%) vs. 7/12 (58.3%); P = 1.00] rates were observed between groups A and B. CONCLUSION: Metformin administration as well as LOD improves the effectiveness of CC for ovulation induction in overweight infertile CC-resistant women with PCOS.

Adult↗
PubMed2006

Intraovarian arterial blood flow resistance in oligomenorrheal infertile women.

PURPOSE: Intraovarian arterial blood flows before and after follicular rupture in ovulation induced cycles were examined by transvaginal color flow Doppler imaging. The changes observed in the intraovarian arterial resistance before and after ovulation in relation to the regularity of menstruation and several other parameters were analyzed. METHODS: In a prospective study, 22 patients undergoing infertility treatment in our center were recruited. Patients were divided into two subgroups, according to their menstrual regularity (regular menstrual group and oligomenorrheal group) and 42 cycles were studied. All patients received the same FSH low-dose stimulation treatment. The relationship between the post and preovulatory arterial pulsatility indexes (PI) was analyzed. Cycles that showed a decrease in their PI after ovulation of 10% or more were considered "profoundly decreased cycles." Cycles from the same patients without ovulatory stimulation (natural cycles) were used as control. RESULTS: In the regular menstrual group the rate of profoundly decreased cycles during FSH stimulation was 63.2%, which was similar to the rate observed in natural cycles. In the oligomenorrheal group the rate of profoundly decreased cycles during natural cycles was 14.3%, but in FSH ovulation induction cycles this rate was significantly increased (47.6%, p < 0.05). In addition, the pregnancy rate per cycle in the oligomenorrheal group was significantly higher than that in the regular menstrual group (p = 0.03). CONCLUSIONS: Oligomenorrheal patients presented a higher rate in the decrease of their PI values after FSH stimulation, which is essential to achieve pregnancy. This elevated rate of reduction implies that oligomenorrheal patients have increased incidence of disturbance in their ovulatory process when compared to normal cycling patients. Thus, ovulation induction with FSH, in oligomenorrheal patients resulted in a higher pregnancy rate in this group.

Adult↗
PubMedDate not supplied

The causes of high-order multiple gestation.

Most recent reviews of multiple gestations have reported that the major cause of triplet and quadruplet pregnancy is therapy with human menopausal gonadotropin (hMG). In an attempt to decrease the number of high-order multiple gestations due to hMG, serial ovarian ultrasound evaluation was introduced in the mid-1970s. To assess the impact of changing technology on the causes of high-order multiple gestation, we reviewed the experience at our institution from 1983 to 1987. During this time period, 35,119 deliveries were performed, including 13 triplet and 2 quadruplet deliveries. Of the triplet and quadruplet pregnancies, 3 (20%) patients conceived spontaneously, 11 (73%) conceived in association with ovulation induction, and 1 (7%) conceived during an IVF cycle. Of the pregnancies associated with ovulation induction, 9 (82%) were associated with clomiphene therapy and only 2 (18%) with hMG therapy. Of the clomiphene patients, 6 (67%) conceived at a dose of 50 mg per day for five days and 5 (55%) conceived during the first cycle. At the present time, in our institution, hMG therapy is no longer the major cause of triplet and quadruplet pregnancies. It is possible that serial serum estradiol and ovarian ultrasound monitoring of hMG cycles has contributed to the low number of hMG-induced triplet and quadruplet pregnancies that we observed.

Adult↗
PubMed2001

Ovarian hyperstimulation syndrome associated with clomiphene citrate.

Ovarian hyperstimulation is a recognized complication of ovulation induction with gonadotrophins. The syndrome is becoming more common as the number of women undergoing in-vitro fertilization increases. It is rarely seen in conjunction with clomiphene citrate usage. This case report is of moderate to severe ovarian hyperstimulation in a patient who was treated with clomiphene citrate because of infertility secondary to anovulation. She presented with amenorrhoea for five weeks, lower abdominal pain and a positive urinary human chorionic gonadotrophin (hCG) test. Pelvic ultrasonography was suggestive of a possible ectopic pregnancy with a differential diagnosis of a ruptured ovarian cyst. Diagnostic laparoscopy was done followed by laparotomy. Oophorectomy was performed because the ovary was thought to be complex with solid areas. However, conservative management with avoidance of laparotomy is the recommendation in confirmed cases of ovarian hyperstimulation but this requires a high level of suspicion in patients who have ovulation induction.

Adult↗
PubMed1999

Growth hormone (GH) substitution in hypogonadotropic, GH-deficient women decreases the follicle-stimulating hormone threshold for monofollicular growth.

The FSH threshold concept for monofollicular growth (which means that at the time the largest follicle reaches 18 mm there are no other follicles with a diameter of 13-18 mm also present) was used during ovulation induction in hypogonadotropic women, who appeared to be GH deficient. This concept was used to investigate whether 1) GH influences the FSH threshold for monofollicular growth and 2) whether such an influence would depend upon the endogenous GH/insulin-like growth factor I (IGF-I)/IGF-binding protein-3 (IGFBP-3) levels. In six hypogonadotropic women the GH response after an insulin challenge did not exceed 6 microg/L. Patients underwent ovulation induction according to a low dose step-up protocol by hMG during two consecutive cycles. GH substitution was provided only during the second cycle. Except for one GH treated cycle, all cycles were ovulatory. IGF-I levels as well as IGFBP-3 levels significantly increased (P < 0.01) during GH substitution. Monofollicular growth was not achieved in the first cycles. In five of six GH-substituted cycles, monofollicular growth was obtained. FSH threshold levels decreased in all patients during GH substitution. The FSH area under the curve was negatively correlated to IGF-I (r = -0.6; P < 0.05) and IGFBP-3 (r = -0.6; P < 0.05). The results of this study indicate that GH may play a role in the physiological growth of the follicle; most likely this occurs by influencing the IGF-I or IGFBP-3 levels. GH appears to selectively increase the sensitivity of the dominant follicle to FSH, facilitating monofollicular growth.

Chorionic Gonadotropin↗
PubMed2001

Clomiphene citrate in the twenty-first century.

Clomiphene citrate is the drug most commonly prescribed for ovulation induction. It is the first choice medication in normogonadotrophic oligo/amenorrhoeic infertility (WHO group 2), essentially associated with polycystic ovaries. Anovulatory women who are responsive to clomiphene citrate should be treated for at least six cycles and the treatment should probably be limited to a maximum of 12 cycles. It is necessary to monitor at least the first cycle with ultrasonography because of the risk of multiple pregnancy and the variable response of patients to different doses of clomiphene. In addition, the risk of ovarian hyperstimulation syndrome should not be underestimated. More triplets and higher order pregnancies result from ovulation induction than from in vitro fertilization, and multiple pregnancy has many risks for both mother and babies. The role of empirical clomiphene in the treatment of unexplained infertility is debatable and the present data are inconclusive. Obesity, hyperandrogenaemia and insulin resistance are important factors in clomiphene-resistant patients. Failure to ovulate in response to clomiphene has been approached by either medical or surgical treatment. An effective alternative medical treatment is gonadotrophin injections. Treatment with metformin and the new generation of insulin-sensitizing drugs is under evaluation. The most widely used surgical treatment today is laparoscopic ovarian drilling, which appears to be as effective as gonadotrophin therapy.

Clomiphene↗
PubMed2004

Laparoscopic ovarian drilling as first line of treatment in infertile women with polycystic ovary syndrome.

Laparoscopic ovarian drilling (LOD) is used as a first line of treatment, as a second line of treatment after patients have proved resistant to clomiphene or as a third line of treatment after failed ovulation induction with gonadotropins. We present the postoperative pregnancy rates of 57 women to evaluate a potential optimal time of LOD together with the other treatment regimens of infertile women with polycystic ovary syndrome (PCOS). Data on the preoperative and operative treatment, and background data were evaluated for their influence on pregnancy rates. The pregnancy rate was 61% among women with PCOS who had LOD. No difference was found in the clinical data between the women who became pregnant and those who did not. Likewise, no difference was found between the women who had pre- and/or postoperative medical ovulation treatment and those who had none. The median time to pregnancy after LOD was 135 days. LOD alone resolves infertility within 4-6 months in 50-60% of couples. A strategy with diagnostic laparoscopy and LOD as the first line of treatment of infertility in women with PCOS will shorten the time to pregnancy for many women, reduce the need for medical ovulation induction and enable diagnosis of those women with anatomic infertility, who can achieve pregnancy only by in vitro fertilization treatment.

Clomiphene↗
PubMedDate not supplied

The influence of hyperestrogenism during in vitro fertilization on the fibrinolytic mechanism.

OBJECTIVE: To evaluate levels of various fibrinolytic factor antigens in women during ovulation induction using controlled ovarian hyperstimulation. METHODS: Plasma tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), and the plasminogen activator inhibitors (PAI-1 and PAI-2) were evaluated and compared with plasma 17 beta-estradiol levels, ranging from 20 pg/mL to > 5,000 pg/mL during the course of treatment. Sixteen patients undergoing IVF were compared prior to (Controls) and following treatment with leuprolide acetate down-regulation followed by menopausal gonadotropin-CG ovulation induction for 14 days. RESULTS: A significant positive correlation was found between tPA and PAI-1 during treatment, while tPA and PAI-1 were negatively correlated with estradiol levels. Mean levels of tPA and PAI-1 significantly decreased as estradiol levels increased. CONCLUSIONS: As the plasminogen activator decreased with increasing estradiol levels, this suggests a potential for thrombosis. However, the major plasminogen activator inhibitor (PAI-1) also decreased; thus, the net clinical effect in terms of increased potential for thrombosis should be minimal. Furthermore, the levels of both tPA and uPA were still within normal ranges. The overall data from this study suggest that ovarian hyperstimulation with fertility-enhancing drugs does not enhance the potential for thrombosis even though there are elevated 17 beta-estradiol levels.

Adult↗
PubMed1995

Treatment by assisted conception of severe male factor infertility due to spinal cord injury or other neurologic impairment.

PURPOSE: This retrospective study evaluated the pregnancy rates of 23 couples with male factor infertility due to traumatic spinal cord injury (N = 21), multiple sclerosis (N = 1) or transverse myelitis (N = 1). METHODS: Ovulation induction by clomiphene citrate or gonadotropins was used in combination with intrauterine insemination as an initial approach for assisted conception in all but one couple. RESULTS: Six pregnancies occurred in 60 cycles of intrauterine insemination (mean of 2.6 cycles). In this group, the cumulative pregnancy rate was 26%. Six couples who failed after a total of 33 intrauterine insemination cycles (mean of 5.5 cycles), and 1 couple with no previous intrauterine insemination cycles, initiated 10 cycles of in vitro fertilization (mean of 1.4 cycles). In this group, five pregnancies occurred. The pregnancy rate was 71%. CONCLUSION: We conclude that ovulation induction in combination with intrauterine insemination offers an effective initial therapy of severe male factor infertility due to spinal cord injury.

Adult↗
PubMed1998

Use of luteinizing hormone releasing hormone agonists in polycystic ovary syndrome.

Luteinizing hormone releasing hormone (LHRH) agonists have been used in conjunction with gonadotrophins, and occasionally with pulsatile LHRH, for ovulation induction in women with clomiphene-citrate-resistant polycystic ovary syndrome (PCOS) and also for superovulation for in vitro fertilization (IVF) and gamete intrafallopian transfer in women with PCOS. In IVF, LHRH agonists given by the 'long protocol' before gonadotrophins are commenced have consistently shown higher pregnancy rates and higher live birth rates. Although the optimal time to commence LHRH agonist is not clearly determined, commencement in the early follicular phase possibly with pre-treatment with the combined oral contraceptive pill would avoid the risk of inadvertent administration during early pregnancy. The role of LHRH agonists in ovulation induction is less clear cut, although there may be some advantages in patients with refractory PCOS. The role of LHRH agonists in ovarian hyperstimulation syndrome and recurrent miscarriage is also discussed.

Abortion, Habitual↗
PubMed2001

Cabergoline influences ovarian stimulation in hyperprolactinaemic patients with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is characterized by abnormal gonadotrophin secretion, in particular an elevated serum concentration of LH, depressed FSH, and an LH/FSH ratio of >or =2. Mild, transient hyperprolactinaemia is frequently associated with PCOS (30% of patients); furthermore, it can be observed during the late follicular and luteal phases of both natural and stimulated cycles. It is suggested that a reduction of the dopamine inhibitory effect might raise both prolactin (PRL) and LH. METHODS AND RESULTS: We compared ovarian stimulation in two groups of hyperprolactinaemic (hyperPRL)-PCOS patients; one group was treated with cabergoline, reducing PRL plasma concentrations to the range normally observed during ovulation induction. In the untreated hyperPRL-PCOS group, we noted a reduced total number of ampoules of recombinant FSH (P < 0.04), fewer days to reach HCG administration (P < 0.04), and significantly higher peak oestrogen plasma concentrations (P < 0.03) compared with the treated group. By ultrasound examination the same group showed significantly higher ovarian volume and an increased total number of follicles of every size. In untreated hyperPRL-PCOS patients, four cycles out of 65 were cancelled due to mild ovarian hyperstimulation syndrome (OHSS) that occurred during ovulation induction. Only one cycle out of 42 in the patients treated with cabergoline was cancelled. No significant differences in pregnancy rate nor in multiple pregnancy were found. CONCLUSION: Our data suggest a dopaminergic control of LH release and support the use of cabergoline in the management of such patients, in order to provide better clinical control of ovarian response and consequently a reduction of the risk of OHSS, with no decrease in pregnancy rate.

Adult↗
PubMed2001

[Can donor insemination be optimised?].

OBJECTIVE: To compare the different donor insemination technics. MATERIAL AND METHOD: Analysis of the published studies about donor insemination which value the effectiveness of Intra Cervical Insemination (ICID) and Intra Uterine Insemination (IUID), the interest of ovulation induction, the possible complications, and the cost-effectiveness ratio. RESULTS: The meta-analysis of the Cochrane data base (10 comparative studies IUID versus ICID, 2568 donor insemination cycles) lead to a pregnancy rate per cycle (PRC) 17.77% with IUID versus 7.68% with ICID. The odds ratio is 2.63 (CI from 1.85 to 3.73). With these PRC, the direct cost per evolutive pregnancy is 54,780 F with ICID and 25,675 F with IUID. CONCLUSION: If it is possible to propose ICID to patient with an excellent regularity of ovulation. IUID with ovulation induction by gonadotropins is today the gold standard, and more especially as the law restrict the number of donor inseminations. Indeed, the IUID is two or three times more effective than ICID, consume the half of sperm straws, use a semen of moderate quality, there is no complication provided that the cycle is cancelled if there is more than two mature follicles and the cost-effectiveness ratio is greatly in favour with IUID.

Cervix Uteri↗