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PubMed1988

Management of multiple conceptions after gonadotropin-releasing hormone analog/human menopausal gonadotropin/human chorionic gonadotropin therapy.

The treatment course of a 31-year-old infertility patient due to PCO disease is presented. Because the patient failed to conceive after various treatment cycles with CC, she was subjected to a combined GnRHa/hMG/hCG therapy. After plasma E2 levels had reached 2400 pg/ml, three leading follicles, with diameters of 20 to 24 mm, were detected. Induction of ovulation was achieved by 10,000 IU hCG. The patient conceived and developed ovarian hyperstimulation. At 8 weeks of gestation, seven cystic structures were detected within the uterine cavity, five containing single embryos, and two with twin embryos. All nine embryos were vital, as evidenced by their heart beats. Embryo reduction was achieved by transabdominal puncture on three occasions. The three surviving fetuses were carried to the 34th week of gestation. After delivery by cesarean section, three healthy babies developed normally. This communication illustrates the complications that can be associated with ovulation induction in PCO disease: ovarian hyperstimulation, polyovulation, multiple conceptions, and their clinical management.

Adult↗
PubMed1979

[The outcome in pregnancies resulting after the induction of ovulation 519 pregnancies (author's transl)].

Some geneticists have been against induction of ovulation because there is a greater incidence of chromosome abnormalities in spontaneous abortions that occur after induced pregnancies. We have found the number of early abortions (15.6 p. 100) and of malformed fetuses (4.8 p. 100) is not greater than average when we have studied a personal prospective series of 140 pregnancies and a series of 519 pregnancies collected following an enquiry made among some of our colleagues. The number of late abortions and of premature labours is much higher (3.4 p. 100 and 14.8 p. 100 respectively) and they correspond particularly with the higher incidence of multiple pregnancies (12.3 p. 100) which have been obtained especially after the use of HMG. This has a direct repercussion on perinatal mortality (4.3 p. 100).

Abortion, Spontaneous↗
PubMed1993

[Simplified management of an in vitro fertilization program].

The development of in vitro fertilization has accelerated in a dramatic way the understanding on gamete physiology. Results obtained with the technique are easily reproducible and consistent between different centers. It is well known that cumulative pregnancy rates with 5 or 6 cycles can reach up to 60% of couples being pregnant. However, the main limitations to successive attempts have been the cost of the procedure and the surgical transfer of the embryos. In an attempt to overcome this difficulties, efforts has been made to simplify the monitoring of induction of ovulation, use of GnRh analogs and non surgical transfers whenever it is possible. Results presented in 47 of these cycles show non significant differences, with data published elsewhere, on oocyte maturity, fertilization and cleavage rates. Moreover pregnancy rates per aspiration are 28.6% and per transfer 33.3%. We can conclude that ultrasonography alone to monitor ovulation induction as well as uterine transfers do not affect the outcome of the cycle.

Adult↗
PubMed2000

Thromboembolic complications associated with reproductive endocrinologic procedures.

Thromboembolism as a complication of hormonal ovarian stimulation in the context of artificial reproductive techniques is rare and seems to occur when OHS is present. Although accompanied by high serum estrogen concentrations, hCG seems to play a central role in the development of OHS, which has been observed in women with 17,18-desmolase deficiency who have low estrogen levels after induction of ovulation with hGC. Although there is some evidence that hormonal ovarian stimulation with HMG, leading to elevated estrogen levels, and ovulation induction with hCG in preparation for in vitro fertilization are associated with a state of hypercoagulability, the exact role of estrogens, hCG and the physicochemical changes (fluid shift into third spaces) involved in OHS remain to be elucidated.

Chorionic Gonadotropin↗
PubMed1999

Attenuation of ovarian response by low-dose ketoconazole during superovulation in patients with polycystic ovary syndrome.

OBJECTIVE: To investigate the clinical efficacy of mild inhibition of ovarian steroidogenesis by very low-dose ketoconazole during induction of ovulation in patients with polycystic ovary syndrome (PCOS). DESIGN: Prospective, randomized, cross-controlled study in consecutive cycles. SETTING: Large tertiary care center. PATIENT(S): Eighteen patients with PCOS undergoing hMG superovulation with or without ketoconazole. INTERVENTION(S): A fixed hMG dosage was initiated on cycle days 5-9 in both of the study cycles. Further hMG adjustment was done according to serum E2 levels and follicular measurements. Ketoconazole was administered in one of the cycles by two protocols. MAIN OUTCOME MEASURE(S): Serum E2 and P levels, lead follicles, pregnancy rate, and development of ovarian hyperstimulation syndrome. RESULT(S): Although higher daily hMG doses were needed in cycles with ketoconazole compared with cycles without the drug, the peak E2 levels were substantially lower in the ketoconazole cycles. Although the number of lead follicles did not differ between treatments, the addition of ketoconazole significantly reduced the number of hyperstimulated cycles. Consequently, the cancellation rate dropped dramatically, thus yielding a higher pregnancy rate per patient in the ketoconazole protocols. CONCLUSION(S): Use of a very low dose of ketoconazole during ovulation induction effectively attenuates ovarian steroidogenesis in patients with PCOS. This effect may serve as an adjunct to better control the ovarian response in women who are prone to hyperstimulated cycles.

Adolescent↗
PubMed2001

Monozygotic twinning after assisted reproductive techniques: a phenomenon independent of micromanipulation.

A 3 year retrospective analysis was conducted of pregnancies achieved after various assisted reproductive treatment modalities in our infertility practice, to calculate and compare the rates of monozygotic twinning (MZT). A total of 731 pregnancies achieved after various assisted reproduction treatments were reviewed. Gonadotrophin therapy for induction of ovulation and controlled ovarian hyperstimulation (COH) yielded 129 clinical pregnancies. Conventional IVF yielded 139 pregnancies. IVF and intracytoplasmic sperm injection (ICSI) with or without assisted hatching (AH) yielded 463 pregnancies, all during the same time period. The rates of multiple pregnancy (monozygotic and dizygotic) twins and triplets were recorded. MZT was found in 1.5% of ovulation induction or COH pregnancies (2/129). The incidence of MZT after conventional IVF was 0.72% (1/139). After IVF-ICSI/AH, MZT was found in 0.86% (4/463). The overall rate of MZT was 0.95% (7/731). Five cases were dizygotic triplets and two cases were monozygotic twins. We found the rate of MZT after assisted reproduction treatment increased more than two-fold over the background rate in the general population. Dizygotic triplets were found more often than monozygotic twins. The rate of MZT was consistently increased, irrespective of treatment modality or micromanipulation. This may signify that the aetiology of increased MZT after assisted reproduction is the gonadotrophin treatment rather than in-vitro conditions, micromanipulation, or multiple embryo transfer.

Adult↗
PubMed1996

Plasma inflammatory cytokines correlate to the ovarian hyperstimulation syndrome.

The objective of this study was to follow the kinetics of four inflammatory cytokines in the plasma and ascitic fluid of seven patients who developed severe ovarian hyperstimulation syndrome (OHSS) after induction of ovulation for in-vitro fertilization. Blood samples were obtained from these patients at three different times: upon hospitalization; when significant clinical improvement was evident; and after complete resolution. Samples were analysed for interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor alpha (TNF-alpha). Ascitic fluid was obtained by therapeutic paracentesis from all study patients during the active phase and analysed for these cytokines. Two control groups were available: the first included 15 women undergoing controlled ovarian stimulation for in-vitro fertilization without developing OHSS, while the second consisted of 25 healthy women not undergoing ovulation induction or any other medical treatment. High concentrations of IL-1, IL-6 and TNF-alpha were detected in all individuals upon admission for severe OHSS. Concentrations dropped significantly along with clinical improvement, reaching normal values after complete resolution. A statistically significant correlation was found between plasma cytokine concentrations and certain biological characteristics of the syndrome such as leukocytosis, increased haematocrit, and elevated plasma 17-beta-oestradiol concentrations. Ascitic fluid obtained from the study patients contained high IL-6 and IL-8 concentrations, while other cytokines were unaltered. These results suggest close association between inflammatory cytokines and the pathophysiology of the ovarian hyperstimulation syndrome.

Adult↗
PubMed1997

[Pre-ovulatory peaks of gonadotropins. Recent data].

From recent data we know that: The duration of the LH peak seems to be more important than its amplitude for the induction of ovulation. Ovulation induction by hCG is not physiological; the absence of an FSH surge, and the long duration of LH activity would contribute to some of the luteal phase abnormalities. Recombinant hLH, on the other hand could give better results provided its action last about 48 hours. The results, however, are not as expected, probably because of the type of isoforms injected. The circulating FSH and LH isoforms found during the preovulatory peak of gonadotropins have a much higher in vitro biological activity than those found at other periods of the cycle. The production of FSH and LH recombinant of different biological activity is in process. The mechanism of the preovulatory peak of gonadotropins is still not fully understood. The respective role of GnRH and of the ovarian steroids has yet to be precisely determined in the human being. Ovarian peptides very probably also play a role.

Animals↗
PubMed1999

Induction of ovulation of mature oocytes by the maturation-inducing steroid 17,20beta,21-trihydroxy-4-pregnen-3-one in the spotted seatrout.

Incubation of mature, hydrated, follicle-enclosed oocytes of the spotted seatrout, Cynoscion nebulosus, with the maturation-inducing steroid (MIS), 17,20beta,21-trihydroxy-4-pregnen-3-one (20beta-S), for 9-12 h resulted in the appearance of ovulated oocytes in the culture media. The ovulation response was concentration-dependent and steroid-specific. The other teleost MIS, 17, 20beta-dihydroxy-4-pregnen-3-one (17,20beta-P), was also a potent inducer of ovulation, whereas progesterone and 11-deoxycorticosterone did not stimulate ovulation above control levels and partially antagonized the action of 20beta-S. The agonist and antagonist activities of these steroids on ovulation are consistent with their relative binding affinities for the ovarian nuclear progestogen receptor previously characterized in this species. Both the RNA synthesis inhibitor actinomycin D and the protein synthesis inhibitor cycloheximide blocked MIS-induced ovulation. This suggests that induction of ovulation by the MIS is through a genomic mechanism of action, and potentially involves the previously characterized nuclear progestogen receptor. Gonadotropin (hCG)-induced ovulation was blocked by addition of the steroid synthesis inhibitor cyanoketone, which was overcome by the addition of 20beta-S, but not pregnenolone. Thus, the most likely mechanism of gonadotropin-induced ovulation is an increase in the synthesis of the MIS. It is concluded that the processes of final oocyte maturation and ovulation are both regulated by the MIS. Whereas final oocyte maturation is mediated by the 20beta-S membrane receptor (P. Thomas and S. Das, 1997, Biol. Reprod. 57, 999-1007), ovulation is regulated by a genomic mechanism and is potentially mediated by the previously characterized nuclear progestogen receptor.

Animals↗
PubMedDate not supplied

[Assisted reproductive technologies after conservative management of borderline or invasive ovarian tumours].

OBJECTIVE: Ovulation induction, the usual resort of Assisted Reproductive Technologies (ART), has been suspected of carrying a responsibility in the genesis of ovarian tumours. For patients with a borderline or invasive ovarian tumour, treated by conservative surgery and desiring to become pregnant, the problem is thus of a possible resort to the Assisted Reproductive Technologies. PATIENTS AND METHODS: This is a multicenter, national and retrospective study. 40 operated patients between January 1971 and January 2001 have been included. 27 patients (67.5%) had a borderline tumour, 10 (25%) a non-epithelial tumour (germinal or stromal) and 3 (7.5%) an epithelial invasive carcinoma. All these patients have benefited from a conservative surgical management of fertility. The Assisted Reproductive Technologies were simple stimulation for 5 women and IVF for the 35 others. The effectiveness and the risks of Assisted Reproductive Technologies have been estimated respectively by the number of pregnancies obtained and the recurrence rates. RESULTS: With a global follow-up of 372 months (January 1971: date of the primary surgical procedure--June 2002: closing of the study), 17 patients have obtained 17 pregnancies with the Assisted Reproductive Technologies, rate of 42.5% (17/40): 1 spontaneous abortion, 16 delivery with 23 children (triple pregnancies and 3 twin pregnancies). 3 patients treated for a borderline tumour have had a recurrence after induction of ovulation. Among the 40 patients, no one presented an evolved disease at the last news. The patients who had a recurrence had a delay to begin the Assisted Reproductive Technologies significantly lower than the patients who had no recurrence. DISCUSSION AND CONCLUSION: The assisted reproductive technologies for patients who had been treated for a borderline or invasive ovarian tumour, and who were infertile in spite of conservative management, have allowed 42.5% of these women to obtain a pregnancy and does not seem to increase significantly the risk of recurrence.

Adult↗
PubMed1988

Persistent ovarian cysts following administration of human menopausal and chorionic gonadotropins: an attenuated form of ovarian hyperstimulation syndrome.

Ovarian cysts persisting after the onset of menses were demonstrated by ultrasound (US) in 40 of 71 (56%) nonconception cycles following ovulation induction with human menopausal gonadotropins (hMG) and human chorionic gonadotropin (hCG). Persistent cysts were self-limited and all resolved spontaneously within two cycles. They developed more frequently during stimulation cycles with (1) higher mean pre-hCG serum estradiol (E2), (2) a greater number of medium and large follicles at peak pre-hCG E2, and (3) a larger leading follicle diameter at peak pre-hCG E2. Persistent ovarian cysts frequently occurred despite a peak pre-hCG E2 lower than 1000 pg/ml. Although ovarian enlargement in the presence of cysts exceeded 5 X 5 cm in 25% of cases, no patient developed clinical symptoms of ovarian hyperstimulation syndrome (OHSS). Repeated induction of ovulation with hMG/hCG in the presence of nonfunctional, persistent cysts resulted in pregnancies in 6 of 15 cases (40%). Asymptomatic persistent ovarian cysts frequently follow an hMG/hCG regimen and, when nonfunctional, are not a contraindication to repeated ovarian stimulation. Persistent ovarian cysts appear to be an attenuated form of OHSS.

Adult↗
PubMed1989

The value of GnRH analogue therapy in IVF in women with unexplained infertility.

Seventy-six women with unexplained infertility, undergoing in-vitro fertilization and embryo transfer (IVF-embryo transfer), were selected for three different ovulation induction protocols. In group I, induction of ovulation was performed with pure follicle-stimulating hormone/human menopausal gonadotrophin/human chorionic gonadotrophin (pFSH/HMG/HCG). Group II patients were given a combined therapy consisting of a gonadotrophin-releasing hormone (GnRH) analogue, decapeptyl (DTRP6) followed by pFSH/HMG/HCG. In group III, patients underwent two IVF-embryo transfer cycles, serving as their own controls. The initial cycle was induced with pFSH/HMG/HCG while the second was stimulated using decapeptyl/pFSH/HMG/HCG. Significantly higher rates of fertilization, cleavage and pregnancy (P less than 0.001, P less than 0.07, P less than 0.001, respectively) were achieved in group II patients to whom combined GnRH agonists and gonadotrophins were given. Furthermore, among group III patients, no pregnancies occurred during the initial IVF-embryo transfer cycles whereas a 23% pregnancy rate (P less than 0.001) was obtained after GnRH agonist therapy. Our results indicate that the combination of GnRH agonists and gonadotrophins is of value in cases of unexplained infertility. Further, larger studies must be performed before the true efficacy of this mode of therapy can be determined in women with unexplained infertility.

Adult↗
PubMed1997

Success rates when attempting to nonsurgically collect equine embryos at 144, 156 or 168 hours after ovulation.

The purpose of this study was to evaluate the exact age when the equine embryo reaches the uterus. The time of ovulation was determined by hourly ultrasound examinations starting 32 h after an injection of crude equine pituitary gonadotrophin or human chorionic gonadotrophin, or after the first of 4 injections of buserelin. Nonsurgical uterine flushings were carried out 144 h (Day 6), 156 h (Day 6.5) or 168 h (Day 7) after ovulation. Induction of ovulation was attempted in 101 oestrous cycles and 61 of 101 mares (60.4%) ovulated 32-44 h post injection. Sixty embryo collections were performed which yielded: 0/20 embryos at 144 h, 9/17 embryos (53%) at 156 h and 12/23 embryos (52%) at 168 h. The mean (+/- s.e.m.) diameter of the embryo was significantly greater (P<0.01) at Day 7 (244 +/- 15 microm) than at Day 6.5 (186 +/- 9.1 microm), and variability in size was observed among embryos collected from the same mare after synchronous natural multiple ovulations. These results suggest that; i) horse embryos enter the uterus between 144 and 156 h after ovulation, and ii) the time interval between ovulation and fertilisation in mares is inconsistent and/or embryonic development rate may differ between individual embryos.

Animals↗
PubMed1995

Collagenolytic enzymes and progestin in induced ovulation in rabbits with hyperprolactinemia.

To clarify the possible role of collagenolytic enzymes and progestin in induced ovulation and to investigate whether progesterone interacts with these enzymes in leading to ovulation during the hyperprolactinemic state, the alterations of 2,4-dinitrophenyl-Pro-Gln-Gly-Ile- Ala Gly-Gln-D-Arg-OH peptidase (DNP-peptidase) and alpha-n-benzoyldl-Arg-beta-naphthylamide hydrolase (BANA-hydrolase) activities were measured in rabbit ovaries. The ovaries were primed with four daily sulpiride (SLP) injections followed by human chorionic gonadotropin (hCG) administration. The peripheral and ovarian progesterone, 20 alpha-hydroxypregn-4-en-3-one (20 alpha OHP) levels and ovulation rate at 14 hours after hCG administration in SLP-treated rabbits were significantly suppressed as compared with the control animals. The usual changes in DNP-peptidase and BANA-hydrolase activities in the follicular tissue at 8 and 10 hours after hCG were also altered by this abnormal hypersecretion of circulating prolactin. When progesterone was administered concomitantly with hCG to the hyperprolactinemic rabbits during ovulation induction, the ovulation rate was restored to a physiologic level comparable to that of the controls. These results suggest that both progesterone and collagenolytic enzymes are mandatory for follicular rupture induced by hCG and that progesterone may interact with these enzymes to facilitate the completion of the ovulatory process during the hyperprolactinemic state.

Animals↗
PubMed1984

Induction of ovulation with gonadotrophins--a ten year review.

We describe the outcome of induction of ovulation with gonadotrophins (HMG/HCG) in 46 patients treated over 138 cycles. Ovulation was induced in 88 per cent of cycles and there were 43 conceptions in 33 patients with a cumulative conception rate of 96 per cent. The incidence of multiple pregnancy was 36 per cent of those reaching a gestation of 13 weeks or more and accounted for all the second and third trimester foetal losses. Overall, 61 per cent of the patients have taken home at least one healthy child. Mild symptomatic ovarian hyperstimulation complicated 9.4 per cent of courses and was more frequent among patients with normal pretreatment oestrogen levels. We found continuous biochemical monitoring of follicular growth to be a poor predictor of multiple pregnancy or hyperstimulation. We discuss our local experience with reference to published reports from other centres and in relation to recent advances in management and consider the future role of this therapy.

Chorionic Gonadotropin↗
PubMed1996

Polycystic ovary syndrome: induction of ovulation.

In summarizing the treatment of infertility associated with PCOS, basically the induction of ovulation may be achieved by boosting FSH stimulation of the ovaries, either indirectly with clomiphene or native pulsatile GnRH, or directly with gonadotrophin preparations. There seem to be two main determinants of the success of this treatment in achieving a live birth: the degree of hyperinsulinaemia and the concentration of circulating LH. Either of these, when in excess, not only makes induction of ovulation and conception relatively difficult but is also associated with a high rate of early miscarriage. Their correction, particularly in obstinate cases, should be a major consideration in the attempt to achieve optimal results. With such a range of reasonably successful treatments for the induction of ovulation in PCOS, the emphasis in the selection of therapy should now be placed on minimizing the prevalence of undesired side-effects while retaining acceptable efficiency.

Anovulation↗
PubMed2000

Growth hormone for in vitro fertilization.

BACKGROUND: Ovulation induction protocols for in vitro fertilization (IVF) are constantly under review and revision in an attempt to decrease gonadotropin requirements while improving follicular recruitment and pregnancy rate. Most studies of the effect of Growth Hormone on ovulation induction have investigated normally ovulating infertile women. Attention has begun to turn to its effect on women who fail to produce an optimal number of follicles in response to ovulation induction. OBJECTIVES: To assess the effectiveness of growth hormone adjuvant therapy for women undergoing ovulation induction prior to IVF in two patient groups: a) those with no previous history of poor response and b) those with a history of poor response. SEARCH STRATEGY: This review has drawn on the search strategy developed for the Subfertility Group as a whole. Relevant trials were identified in the Group's Specialised Register of Controlled Trials. See Review Group details for more information. SELECTION CRITERIA: All RCTs were included if they addressed the research question posed and provided outcome data for intervention and control subjects. Outcomes of interest included pregnancy, oocyte/embryo number and peak estradiol level. DATA COLLECTION AND ANALYSIS DATA EXTRACTION: A diverse search strategy was employed, including hand-search of 43 core journals from 1966 to the present, bibliographies of relevant trials, MEDLINE database, abstracts from North American and European meetings and contact with authors of relevant papers. Relevant data were extracted independently by two reviewers using the standardized data extraction sheet. Validity was assessed in terms of method of randomization, completeness of follow-up, presence or absence of crossover and co-intervention. DATA SYNTHESIS: 2x2 tables were generated for all relevant outcomes. Odds ratios were generated using the Peto modified Mantel-Haenszel technique. Statistical heterogeneity was assessed using x2. MAIN RESULTS: In women with no previous history of poor stimulation, the common odds ratio for pregnancy per cycle was 0.97 (95% CI 0.34-2. 76) Total dose of gonadotropin and number of oocytes retrieved were similar between treated and placebo groups. In previous poor responders, the common odds ratio for pregnancy per cycle instituted was 2.55 (95% CI 0.64-10.12). Again, no statistically significant difference was noted in gonadotropin dosage or oocyte number obtained, when all studies were considered. REVIEWER'S CONCLUSIONS: Data from 6 small trials suggest that in women with no previous poor response, GH augmentation does not improve the rate of pregnancy. In poor responders, a trend towards improved outcome with GH treatment deserves further study.

Female↗
PubMed1979

[Serial determination of hormones in pregnancies following induction of ovulation with clomiphene and gonadotropins (author's transl)].

The HCG, HPL, progesterone and oestriol levels in the serum were determined in 33 pregnancies following induction of ovulation with clomiphene and in 7 pregnancies following induction of ovulation with gonadotropins. During these pregnancies bleeding, premature labour and toxaemia occurred more often in women who became pregnant after induction of ovulation with clomiphene. The progesterone and oestriol levels were increased up to the 12th week of gestation, whereas the HCG and HPL levels remained normal. After induction of ovulation with gonadotropins the progesterone levels remained elevated until the 19th week of gestation whereas the levels of HCG and HPL and oestriol remained normal. The course of the pregnancy in a patient who had Meigs-syndrome after treatment with gonadotropins was presented. Our results show that the hormonal evaluation of pregnancies after induction of ovulation is best accomplished during the first three months by HCG and HPL titres and during the second half of the pregnancy according to the same criteria as in other pregnancies.

Adult↗