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PubMed2005

An economic evaluation of laparoscopic ovarian diathermy versus gonadotrophin therapy for women with clomiphene citrate-resistant polycystic ovarian syndrome.

PURPOSE OF REVIEW: Women with polycystic ovarian syndrome are typically anovulatory and require ovulation induction. Ovarian wedge resection was the first treatment for anovulation but was eventually abandoned because of the increased risk of postsurgical adhesions and as medical ovulation induction with clomiphene and gonadotrophins was introduced. However, with the advent of laparoscopy, there has been a return to surgical approaches. The potential advantages of laparoscopic surgery include avoidance of hyperstimulation and the lowered costs make ovarian surgery an attractive alternative to gonadotrophins. RECENT FINDINGS: Clinical trials in New Zealand and the Netherlands have compared costs of laparoscopic ovarian drilling with gonadotrophins. The total cost of treatment in the Netherlands study for the ovarian drilling group was euro 4664 and for the gonadotrophins group was euro 5418. Without the cost of monitoring and the diagnostic laparoscopy then the difference was euro 2110 in favour of ovarian drilling. It was estimated that the cost per term pregnancy would be euro 14,489 for gonadotrophin and euro 11,301 for ovarian drilling (22% lower). The higher rates of multiple pregnancy in the gonadotrophin group were considered to be responsible for the increased costs. In the New Zealand trial the costs of a live birth were one-third lower in the group that underwent laparoscopic ovarian diathermy compared with those women who received gonadotrophins (NZ$19,640 and 29,836, respectively). SUMMARY: Treating women with clomiphene-resistant polycystic ovarian syndrome with laparoscopic ovarian diathermy results in reduced direct and indirect costs. The reduction in multiple pregnancies makes the alternative of surgery particularly attractive.

Cost-Benefit Analysis↗
PubMed2004

Management of anovulatory infertility associated with polycystic ovary syndrome: tamoxifen citrate an effective alternative compound to clomiphene citrate.

Clomiphene citrate (CC) is widely used as first-line treatment for ovulation induction in anovulatory women with polycystic ovary syndrome (PCOS). Tamoxifen citrate (TMX), another non-steroidal selective estrogen receptor modulator, may also be effective on the resumption of ovulation in these women. The aim of this controlled observational study was to compare the efficacy and safety of ovulation induction with TMX versus CC in anovulatory infertile women with PCOS. A total of 102 consecutive women (mean age+/-SD: 31+/-3.6 years; range: 26-38) with PCOS were studied. Following a spontaneous or progesterone-induced withdrawal bleed, women received either 50 mg daily of CC (days 2-6) or 20 mg daily of TMX (days 2-5). In case ovulation failed to occur, the dose was sequentially increased to 100 mg daily of CC and 40 mg daily of TMX, respectively. Serum progesterone levels were measured on cycle day 21 to monitor the ovulation pattern. The overall ovulation rate was significantly higher in women who received TMX compared with those who received CC (61/98, 62.2% vs. 60/127, 47.2%, p=0.03). Although not statistically significant, the pregnancy rate per ovulatory cycle was higher in the TMX group compared to the CC group (14/61, 22.9% vs. 11/60, 18.3%, respectively). All pregnancies were single and there were no side-effects in either group of treatment. Collectively, these data demonstrate that TMX is a safe and effective agent, and a suitable alternative to CC for anovulatory infertility in women with PCOS.

Adult↗
PubMedDate not supplied

Growth hormone treatment in infertility: a short review.

In cultured animal granulosa cells, insulin-like growth factor 1 (IGF-1) and growth hormone (GH) have been shown to have a functional role. With the recent availability of recombinant GH, clinical studies have followed using GH in ovulation induction in patients resistant to stimulation by gonadotrophins alone. So far, patient numbers have been small in the studies conducted but the results suggest that GH may improve ovulation induction and reduce gonadotrophins requirement. However, patients with GH deficiency are not infertile. Thus the evidence suggests that the role of GH treatment in infertility is probably facilitative and not obligatory.

Female↗
PubMed2002

Practice patterns among board-certified reproductive endocrinologists regarding high-order multiple gestations: a united states national survey.

OBJECTIVE: To assess current practice management, attitudes, and strategies of reproductive endocrinologists in the United States regarding high-order (at least three) multiple gestations. METHODS: Questionnaires were mailed to 768 board-certified reproductive endocrinologists of whom 722 were eligible for the study. The questionnaires addressed topics such as practitioner demographics, management strategies, and attitudes regarding high-order multiple gestations. RESULTS: The survey response rate was 52%. Most physicians performed 100-300 cycles of each ovulation induction with intrauterine insemination and in vitro fertilization in 1998 and 1999. The most commonly reported incidence of high-order multiple gestations resulting from each ovulation induction with intrauterine insemination and in vitro fertilization was 2-5% in 1998 and 1999. Strategies used to decrease the rate of high-order multiple gestations varied among practitioners. Informed consent regarding high-order multiple gestations was provided by 99.5% of practitioners. Information regarding selective reduction was provided by 98.3% of respondents. Over 90% of practitioners believed it is worthwhile to attempt to decrease the risk of high-order pregnancies at the risk of decreasing their group's overall pregnancy rates. CONCLUSION: Most reproductive endocrinologists reported concern over the rising risk of high-order multiple gestations resulting from therapies such as superovulation with intrauterine insemination or in vitro fertilization. However, the ways in which patients are counseled regarding such events, their sequelae, and methods to avoid them greatly differ among respondents. Given the inconsistent practice patterns, a multifaceted educational approach may provide an opportunity to reduce the incidence of high-order multiple gestations and their sequelae.

Counseling↗
PubMed1997

Right or left ovary--which one is better?

This study tests the hypothesis that there is a different response after gonadotrophin-releasing hormone and human menopausal gonadotrophins (GnRH/HMG) stimulation for in-vitro fertilization (IVF) in patients with either a right or left ovary. A total of 56 cycles in 44 women after left oophorectomy (group A) was compared with 42 cycles in 29 women following right oophorectomy (group B). Tubal disease was the sole cause of infertility in all cases. The two groups were similar in age. There was no difference in total amount or days of HMG required for ovulation induction, peak oestradiol concentrations, number of oocytes retrieved and fertilization rate. The pregnancy rate was identical in the two groups (20.0 and 20.9% respectively). Our results indicate that with GnRH/HMG ovulation induction protocol for IVF there is no predilection of one ovary over the other.

Adult↗
PubMed1998

The origin of serum progesterone during the follicular phase of menotropin-stimulated cycles.

The study was designed to investigate the source of progesterone secretion during pituitary suppression and ovarian stimulation. It involved 416 women undergoing in-vitro fertilization (IVF) who were treated with gonadotrophin-releasing hormone agonist (GnRHa) and human menopausal gonadotrophin (HMG) (group I), 139 women undergoing ovulation induction with HMG only (group II) and nine women who were diagnosed previously as late-onset adrenal hyperplasia and treated continuously with dexamethasone, in addition to ovulation induction (group III). During HMG treatment, serum oestradiol and progesterone were measured every 1-2 days. If progesterone concentration exceeded 3.0 nmol/l, at least 36 h before human chorionic gonadotrophin (HCG) administration, the patients were prospectively randomized to treatment with dexamethasone or not and the hormones concentrations were measured again 12 h later. Mean age and pretreatment serum concentrations of dehydroepiandrosterone sulphate, androstenedione, testosterone and luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio, were not significantly different in the patients with and without progesterone elevation. Pituitary down-regulation did not reduce the incidence of progesterone elevation (13.9 and 12.2% in groups I and II respectively), while in group III, progesterone concentrations did not increase. After dexamethasone administration a significant decrease in serum progesterone concentration was demonstrated (mean +/- SD, -2.1 +/- 1.4 and -1.6 +/- 1.2 in groups I and II respectively, while in the untreated patients it increased (+1.9 +/- 1.9 and +4.2 +/- 4.8). The increase in serum progesterone concentrations was not accompanied by an increase in cortisol and 11-deoxycortisol but by an increase in LH. After dexamethasone administration the concentrations of cortisol, 11-deoxycortisol and LH significantly decreased. Progesterone concentration was positively correlated with both oestradiol concentration (r = 0.290; P < 0.05) and the number of oocytes retrieved (r = 0.207; P < 0.05). We conclude that at least a part of serum follicular-phase progesterone appears to be of adrenal origin. High oestrogen concentrations (or other ovarian factors) may cause changes in the hypothalamic-pituitary-adrenal axis and in adrenal enzyme activity as a part of the complex 'cross-talk' between the hypothalamic-pituitary-ovarian and the hypothalamic-pituitary-adrenal axes.

Adrenocorticotropic Hormone↗
PubMed1991

Examination of the follicular maturation influencing effect of Clostilbegyt by endocrinous and electronic monitoring.

The follicle maturation influencing effect of Clostilbegyt (50 mg Clomiphene-citrat) has been examined in 30 women suffering from primary or secondary sterility. For monitoring follicular development a vaginal ultrasound scanner was used. The development of yellow body and its adequate function have been controlled with serum progesterone determination. In the first therapeutical cycle daily 1 tbl. Clostilbegyt was used from the 4th day of the menstruation in a five day period. In the next cycle daily 2 tbl. were administered similarly. If the therapy was unsuccessful, then 3 tbl. per day Clostilbegyt was used as treatment in the 3rd cycle. In the course of monitoring with vaginal ultrasound scanner successful ovulation induction has been proved in 80% of the Clostilbegyt treated cases (in 24 of 30 cases). During the examination period pregnancy occurred in 7 cases (29.2%). Vaginal ultrasound monitoring is recommended by the author for ovulation induction therapy.

Adult↗
PubMed1994

[Perinatal outcome of pregnancies following therapy of infertility].

To evaluate the risks involved in post infertility pregnancy, the perinatal outcomes of 571 patients with infertility treatment in 9 institutions were analyzed by questionnaire retrospectively. The rate of multiple pregnancy and premature delivery was 14.5% (83/571) and 13.3% (76/571) respectively. Multiple pregnancies occurred in 33 cases with ovulation induction, 22 cases with artificial insemination by the husband (AIH) and 25 cases with in-vitro fertilization by embryo transfer (IVF). Premature deliveries occurred in 32 cases with ovulation induction. 26 cases with AIH and 14 cases with IVF. Three babies were dead and 4 babies were handicapped. In single post infertility pregnancy, the rate of premature birth was twice as high (9.0%) as in normal controls. The mortality rate was 0.45% (2/449), which was higher than that of controls. This suggests that post infertility pregnancies tend to result in multiple pregnancy and premature birth. In addition, in single post infertility pregnancies there was the possibility of poor perinatal outcome.

Adult↗
PubMed2006

Similar ovulation rates, but different follicular development with highly purified menotrophin compared with recombinant FSH in WHO Group II anovulatory infertility: a randomized controlled study.

BACKGROUND: The contribution of the LH activity in menotrophin preparations for ovulation induction has been investigated in small trials conducted versus FSH preparations. The objective of this study was to demonstrate non-inferiority of highly purified urinary menotrophin (HP-HMG) versus recombinant FSH (rFSH) with respect to the primary outcome measure, ovulation rate. METHODS: This was a randomized, open-label, assessor-blind, multinational study. Women with anovulatory infertility WHO Group II and resistant to clomiphene citrate were randomized (computer-generated list) to stimulation with HP-HMG (n=91) or rFSH (n=93) using a low-dose step-up protocol. RESULTS: The ovulation rate was 85.7% with HP-HMG and 85.5% with rFSH (per-protocol population), and non-inferiority was demonstrated. Significantly fewer intermediate-sized follicles were observed in the HP-HMG group (P<0.05). The singleton live birth rate was comparable between the two groups. The frequency of ovarian hyperstimulation syndrome and/or cancellation due to excessive response was 2.2% with HP-HMG and 9.8% with rFSH (P=0.058). CONCLUSIONS: Stimulation with HP-HMG is associated with ovulation rates at least as good as a rFSH in anovulatory WHO Group II women. LH activity modifies follicular development so that fewer intermediate-sized follicles develop. This could have a positive impact on the safety of ovulation induction protocols.

Adolescent↗
PubMed1997

Vascular endothelial growth factor plasma levels correlate to the clinical picture in severe ovarian hyperstimulation syndrome.

OBJECTIVE: To assess the potential involvement of vascular endothelial growth factor in the hyperpermeability characterizing the ovarian hyperstimulation syndrome (OHSS). DESIGN: A controlled clinical study that followed the kinetics of vascular endothelial growth factor in the plasma of patients with severe OHSS from the time of admission to the hospital and until clinical resolution. SETTING: Women hospitalized with severe OHSS in a tertiary medical center. PATIENT(S): Seven patients with severe OHSS after ovulation induction for IVF and seven controls who had received a similar ovulation induction regimen and did not develop the OHSS. INTERVENTION(S): Three blood samples were obtained from each OHSS patient: upon hospitalization for severe OHSS, when significant clinical improvement was evident, and on the first follow-up visit after the patients' discharge. Ascitic fluid was obtained from all OHSS patients by therapeutic paracentesis during the active phase of the syndrome. Blood samples were drawn from the control patients 4 to 6 days after ET. All samples were assayed for vascular endothelial growth factor levels, hematocrit, E2 levels, and white blood cell count. MAIN OUTCOME MEASURE(S): Vascular endothelial growth factor levels were assayed by ELISA. Estradiol was determined by RIA. RESULT(S): Compared with the controls, high levels of vascular endothelial growth factor were detected in the plasma of all patients admitted for severe OHSS. Levels dropped significantly along with clinical improvement, reaching minimum values after complete resolution. A statistically significant correlation was found between plasma vascular endothelial growth factor levels and certain biologic characteristics of OHSS and of capillary leakage such as leukocytosis and increased hematocrit. Ascitic fluid obtained from the study patients also contained high vascular endothelial growth factor levels. CONCLUSION(S): These findings suggest the involvement of vascular endothelial growth factor in the pathogenesis of capillary leakage in the OHSS.

Adult↗
PubMed1986

Cross-over trial of superovulation protocols from two major in vitro fertilization centers.

A study was undertaken as a controlled comparison of two different superovulation induction protocols currently in use in major Australian in vitro fertilization (IVF) clinics. Thirty patients each from the Monash University and the Royal Women's Hospital (RWH) IVF programs were stimulated for ovulation induction by the other program. Once timing for oocyte retrieval was scheduled, all care reverted to the program from which the patient first came. Results given as pregnancies per patient commencing stimulation were: RWH patients on Monash protocol, 27%; RWH control patients, 15%; Monash patients on RWH protocol, 7%; Monash control patients, 13%. In the year preceding the trial pregnancy rates were 16.9% at Monash and 10.6% at RWH. Stimulation protocols were also compared with respect to each of administration, cost, and patient stress. The results of this cross-over trial demonstrated major differences between the two ovulation induction protocols studied, although it was not possible to conclude that differences in pregnancy rate were due to stimulation alone.

Adult↗
PubMed1996

Elevated liver function tests in a case of moderate ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome is a recognized complication of ovulation induction. Abnormalities in liver function have been considered to be a rare manifestation of the severe form of ovarian hyperstimulation syndrome (OHSS). A 28 year old woman with primary infertility underwent ovulation induction and intrauterine insemination. She was diagnosed with moderate OHSS and was followed as an outpatient. Early in her course of treatment she complained of upper right quadrant pain. Her work-up included an upper right quadrant ultrasound which showed only moderate ascites. Liver function tests at that time were elevated in a hepatocellular damage pattern. Liver function test elevations, as well as the ovarian hyperstimulation, resolved spontaneously in 10 days. Transient abnormalities in liver function do not appear to be limited to the most sever forms of OHSS.

Adult↗
PubMed1990

Serum levels of pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG), a glycosylated beta-lactoglobulin homologue, in successful and unsuccessful assisted conception.

Pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG) is the major secretory protein of the endometrium in the late luteal phase. Serum levels were measured during the implantation period in successful and unsuccessful cycles of assisted conception. The effects of two different treatment regimens were also compared. All patients who underwent ovulation induction therapy showed an endometrial response as measured by a rise in serum levels of alpha 2-PEG. This rise was the same regardless of either implantation or the method of ovulation induction used. Higher levels were seen at oocyte recovery in those cycles treated with clomiphene citrate and may reflect a disordered endometrial response involving a direct effect of the drug on the endometrium. This may explain the difference in success rates in assisted conception when an alternative treatment initially involving down-regulation of endogenous gonadotrophin activity and subsequent administration of gonadotrophins is used. The rise in serum levels seen in pregnancy did not differ statistically according to whether the pregnancy progressed normally or subsequently aborted. Considerably reduced alpha 2-PEG production by the endometrium was identified in one patient who subsequently aborted. The measurement of serum levels of alpha 2-PEG during the implantation phase is unlikely to provide a clinical tool either for early detection of pregnancy or as a prognostic factor of successful implantation.

Abortion, Spontaneous↗
PubMed1997

Successful birth after intrafallopian transfer of microhatched embryos.

OBJECTIVE: To present a successful transfer of microhatched embryos to the fallopian tubes via microlaparoscopy. DESIGN: Case report. SETTING: Private practice affiliated with a medical university. PATIENT: A 40-year-old woman with primary infertility, mildly elevated baseline FSH levels, and a history of poor ovarian response to ovulation induction. Her husband had severe oligoospermia after vasectomy reversal. INTERVENTION(S): Late luteal leuprolide acetate to pituitary down-regulation followed by pure FSH, 300 IU, and hMG, 300 IU, daily for ovulation induction. Transvaginal oocyte retrieval, intracytoplasmic sperm injection, assisted embryo hatching, microlaparoscopic intrafallopian ET. MAIN OUTCOME MEASURE(S): Amniocentesis at the 14th week of gestation revealed a normal karyotype (46,XX), birth of a normal female infant (3700 g). RESULT(S): Establishment of a single, viable intrauterine gestation followed by a vaginal delivery at term. CONCLUSION(S): This case shows the possibility of using assisted-hatched embryos for laparoscopic intrafallopian tube transfer.

Adult↗
PubMed1995

Gonadotrophin surge-attenuating factor bioactivity is present in follicular fluid from naturally cycling women.

Rat pituitary monolayer bioassays were used to compare gonadotrophin surge-attenuating factor (GnSAF) bioactivity in follicular fluid from 12 follicles in 10 spontaneously cycling women with that in pooled follicular fluid from women undergoing ovulation induction. Expressed as ED50S (microliter follicular fluid/well producing 50% of maximal effect), GnSAF bioactivity was detectable in all spontaneous follicular fluid samples (1.4-33.3 microliters/well) and in follicular fluid from women undergoing ovulation induction (6.8 microliters/well). This GnSAF bioactivity was unaffected by pre-incubation with an inhibin antibody. When the data were grouped according to whether the recovered oocytes fertilized in vitro or not, the fertilized group contained significantly greater GnSAF bioactivity than the unfertilized group (5.3 +/- 1.1 and 14.1 +/- 2.6 microliters/well respectively, P < 0.05). While both inhibin bioactivity (9.7 +/- 1.4 and 28.9 +/- 12.1 microliters/well) and immunoreactivity (36.8 +/- 2.2 and 21.0 +/- 3.0 and ng/ml) were also greater (P < 0.01) in the fertilized compared with the unfertilized groups respectively, there were no other significant differences between the two groups. We conclude that GnSAF is found in follicular fluid from spontaneously cycling women, supporting in-vivo evidence for the involvement of GnSAF in feedback control of the ovary-pituitary axis.

Adult↗
PubMed1994

Comparison of leuprolide acetate and human chorionic gonadotropin for the induction of ovulation in clomiphene citrate-stimulated cycles.

OBJECTIVE: To examine the relative efficacies of leuprolide acetate (LA) and hCG in inducing ovulation and a normal luteal phase during clomiphene citrate (CC)-stimulated superovulation cycles. DESIGN: Prospective, randomized, blinded, and cross-controlled in consecutive cycles. SETTING: Large military tertiary care center. PATIENTS: Twenty-one ovulatory patients undergoing superovulation with CC and IUIs for the treatment of unexplained or male factor infertility. INTERVENTIONS: Clomiphene citrate (100 mg/d) on cycle days 5 through 9 in both of the study cycles. Administration of 2 mg SC LA in one cycle and 10,000 IU IM hCG in another cycle for induction of the midcycle surge. MAIN OUTCOME MEASURES: Serum LH, FSH, E2, and P levels every 12 hours for 36 hours after administration of either LA or hCG to characterize the midcycle hormonal dynamics. Luteal phase duration and serum P levels during the midluteal phase were used to estimate the adequacy of the luteal phase. Serial ultrasounds also were done to determine the incidence of luteinized unruptured follicle syndrome. RESULTS: Serum FSH levels in the periovulatory interval were significantly higher after the administration of LA. There were no differences in the periovulatory E2 or P levels or the incidence of sonographic evidence of ovulation after administration of either LA or hCG. Although midluteal serum P levels were higher in the cycles in which hCG was administered, all 42 treatment cycles had adequate luteal phases as assessed by luteal phase duration and three midluteal P levels. Ongoing pregnancies occurred after both LA- and hCG-stimulated cycles. CONCLUSION: Leuprolide acetate and hCG were equivalent in their abilities to induce ovulation. Further evaluation of the adequacy of the luteal phase and the ensuing pregnancy rates after LA induction of an endogenous gonadotropin surge are indicated.

Adult↗
PubMed1998

Increase in serum leptin concentrations in women undergoing controlled ovarian hyperstimulation for assisted reproduction.

The ob gene product might influence the hypothalamo-pituitary axis and ovarian function directly via specific ovarian receptors. Premenopausal women have higher leptin concentrations compared to postmenopausal controls. In this study, we determined changes in leptin serum concentrations under the influence of supraphysiological estradiol levels during controlled ovarian hyperstimulation. In a prospective study of 20 patients undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), morning blood samples were collected to determine leptin and estradiol concentrations on day 3 and day 9 of the stimulation cycle and on alternate days until ovulation induction. There was a significant increase in serum leptin concentrations from day 3 to day 9 (9.87 +/- 1.5 ng/ml on day 3 and 13.8 +/- 2.1 ng/ml on day 9 respectively). No further increase in leptin was observed until the day of ovulation induction. These data further underline the role of leptin as a hormone of reproduction.

Adult↗
PubMed1981

Triplet and quadruplet pregnancies and management.

The rate of multiple pregnancies with more than 2 fetuses has significantly increased since the introduction of ovulation induction agents. From 1970 through 1978, there were 19 triplets and 6 quadruplets in the authors' department, incidences of 1:696 and 1:5370, respectively. Eighteen (72%) of the 25 multiple pregnancies followed treatment with ovulation induction agents and 7 were spontaneous. The diagnosis of more than 2 fetuses was made earlier in the induced than in the uninduced pregnancies. Management, initiated upon diagnosis, included bed rest, high-protein diet, beta-mimetic agents, progestins, dexamethasone late in the second trimester, and selective cerclage. The mean gestational age was 34 weeks in the triplets and 35 weeks in the quadruplets. Forty-four percent of the deliveries were by cesarean section and the remainder were by vaginal delivery. The mean weight of the neonates was 1807 g in the triplets and 1950 g in the quadruplets. The mean overall Apgar score was 8.16, and the perinatal mortality was 185 per 1000, corrected (more than 28 weeks) to 137 per 1000. The main neonatal complications resulted from prematurity, and maternal complications noted were postpartum hemorrhage necessitating hysterectomy in 2 patients. The preferable mode of delivery cannot be stated dogmatically. Fetal outcome was similar in vaginal and cesarean deliveries among the various gestational age groups.

Adult↗