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PubMed1989

The polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a multifaceted clinical entity the hallmark of which is ovulatory dysfunction associated with a relative luteinizing hormone excess and follicle-stimulating hormone (FSH) deficiency. Clomiphene citrate has been the first-line drug for ovulation induction in women with PCOS: because it is an attenuated estrogen, its action blocks the acyclic estrone effect in PCOS. However, many women fail to ovulate or conceive on clomiphene, and an appropriate agent for them was unavailable until relatively recently. The use of a "pure" FSH preparation, Metrodin, provides physiologic replacement of the deficient gonadotropin in PCOS; thus, Metrodin is the ideal second-line drug. Its use with a low-dose regimen should avoid the hyperstimulation seen with human menopausal gonadotropin in PCOS; spontaneous ovulation is an end point. Thus, PCOS patients who do not achieve pregnancy with clomiphene citrate have available a new, more physiologic approach to ovulation induction.

Clomiphene↗
PubMed1998

Borderline tumors of the ovary: fertility treatment, conservative management, and pregnancy outcome.

BACKGROUND: Ovarian tumors of borderline malignancy have a less aggressive behavior and tend to occur at a younger age than their invasive counterparts. The role and extent of fertility-sparing conservative treatments is under continuous evaluation. METHODS: The current study was a retrospective review of 82 patients with confirmed borderline tumors diagnosed over a 25-year period, with special focus on fertility-associated issues. RESULTS: Follow-up was available for 96% of the patients, for a total of 357 women-years of follow-up. Thirty-nine patients underwent conservative management. Of these, only three patients had a contralateral recurrence. Two of the three again opted for conservative management and were without evidence of disease at last follow-up. Seventeen patients did benefit from contralateral ovarian dissection either by cystectomy or oophorectomy because of contralateral benign or borderline disease. Eleven patients had received or were scheduled to receive ovulation induction. Five patients were diagnosed during the evaluation, and another two were diagnosed so soon after the initiation of ovulation induction that a causative relationship appeared to be unlikely. Six patients were diagnosed during ongoing pregnancies. Twenty-two pregnancies were achieved in 15 patients after conservative treatment. No influence of the disease or its treatment on the pregnancy (or vice versa) was observed during a mean follow-up of 69 months. CONCLUSIONS: Data are accumulating that indicate conservative fertility-sparing disease management is adequate treatment for patients with borderline tumors. Available data indicate that in these patients fertility, pregnancy outcome, and survival remain excellent.

Adenocarcinoma, Mucinous↗
PubMed2002

Surgical or medical treatment of polycystic ovary syndrome: a cost-benefit analysis.

With the availability of laparoscopic ovarian cautery, there has been a resurgence in interest in the surgical treatment of clomiphene citrate-resistant polycystic ovary syndrome (PCOS). Comparison of ovulation and pregnancy rates has found no difference in success rates between ovarian cautery and gonadotropin ovulation induction for such women. We have therefore compared the cost of laparoscopic ovarian cautery with that of a typical cycle of gonadotropin ovulation induction, and also found that there is little difference. Because of the potential advantages of ovarian cautery, we recommend this surgery as the next line of treatment if clomiphene citrate fails to induce ovulation in PCOS patients, before gonadotropins are introduced.

Cautery↗
PubMed1994

Induction of pre-ovulatory luteinizing hormone surge by gonadotrophin-releasing hormone agonist for women at risk for developing the ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) is a major risk in patients undergoing ovulation induction protocols. Withholding injection of human chorionic gonadotrophin (HCG) may prevent the development of OHSS, but can also result in failure to ovulate and conceive. We have used a gonadotrophin-releasing hormone agonist (GnRHa) as an alternative to HCG in women not undergoing in-vitro fertilization in an attempt to prevent OHSS. The study included 12 cycles in 12 women scheduled for ovulation induction with human menopausal gonadotrophin (HMG) who were at risk of developing OHSS (oestradiol > 3500 pg/ml, number of follicles > 20). GnRHa was injected to induce the pre-ovulatory, luteinizing hormone surge which triggers follicular maturation. Progesterone was administered for luteal support. Six pregnancies were achieved, and none of the 12 women developed OHSS. Since the pregnancy rate in this study was acceptable, we can recommend the use of GnRHa instead of HCG in any case at risk of developing OHSS.

Estradiol↗
PubMed1989

[Clinico-hormonal characteristics of patients with hypogonadotropic amenorrhea].

Clinical examinations including morphometry, mammography, x-ray examination of the cranium, ultrasonic examination of the small pelvic organs help detect the patients with hypogonadotropic amenorrhea and predict the efficacy of ovulation induction with menopausal gonadotropin. Women with a positive reaction to administration of progesterone and LH releasing factor make up the group most promising in respect of ovulation induction with menopausal gonadotropin.

Adult↗
PubMed1993

Acardius acephalus after induced ovulation: a case report.

An excess of structural defects occurs in monozygotic twins compared to dizygotic twins or singletons. Among these defects the acardius acephalus or chorangiopagus parasiticus is one of the most rare and severe and a possible cause of pathology to the other twin. Ovulation induction by clomiphene causes an increased frequency of multiple gestation and possibly of monozygotic multiple pregnancy. In the present report, we describe a prenatally diagnosed and autopsied case of acardius acephalus from a pregnancy established after ovulation induction by clomiphene. Approximately 1.4% of pregnancies are accomplished after use of ovulation inducing medication in the Netherlands. A possible etiological role of clomiphene justifies close monitoring of future cases.

Abnormalities, Multiple↗
PubMed1991

Controlled ovarian hyperstimulation as a risk factor for ectopic pregnancy.

As part of a case-control study of ectopic pregnancy, we evaluated the potential etiologic role of controlled ovarian hyperstimulation in a population with no previous history of ectopic pregnancy. Ovulation induction alone was associated with an increased risk of ectopic pregnancy (adjusted odds ratio = 3.98; 95% confidence interval 1.10-14.30). In contrast, ovulation induction for in vitro fertilization did not increase the risk further (adjusted odds ratio = 2.45; 95% confidence interval 0.54-11.13). These results suggest that hormonal factors may be involved in the development of ectopic pregnancy.

Adult↗
PubMed2001

Clinical pregnancy rates in an IVF program. Use of the flare-up protocol after failure with long regimens of GnRH-a.

OBJECTIVE: To examine the efficacy of flare-up protocols in patients who failed to respond to a long protocol using gonadotropin-releasing hormone agonist (GnRH-a). STUDY DESIGN: In this retrospective study, a total of 144 patients who underwent an in vitro fertilization/embryo transfer cycle with the flare-up protocol were analyzed. Of these, 111 patients (group I) had not responded well to ovulation induction with long-term down-regulation with GnRH-a (long protocol), and 33 (group II) had responded to ovulation induction with at least four follicles but failed to conceive after embryo transfer. The average age of the patients were 37.3 +/- 3.9 years (range, 28-43) and 36.5 +/- 3.7 (range, 24-44), respectively. All patients underwent a flare-up protocol with GnRH-a (leuprolide acetate, 0.5 mg/d) on day 2 and at least 6 ampules of gonadotropins on day 3 within 6 months following failure with the long protocol. Unresponsiveness was defined as having fewer than three developing follicles on day 7, with an estradiol level < 200 pg/mL. Patients with a cycle day 2 follicle stimulating hormone (FSH) level > 15 mIU/mL before initiating GnRH-a were not included in the flare-up protocol. The average day 2 FSH levels of the patients on the flare-up protocol cycles were 9.1 +/- 3.0 in group I and 7.1 +/- 2.0 in group II. RESULTS: In group I, 44 of 111 (39.6%) patients did not respond to the flare-up protocol even with an increased dose of gonadotropins. In 67 patients, an average of 7.2 +/- 2.3 oocytes were obtained. Embryo transfer was performed on 64 patients with an average of 3.2 +/- 0.6 embryos. Fertilization did not occur in three patients. Eleven women conceived, eight of them miscarried, and three delivered. The pregnancy rate per cycle initiated was 9.9% (11/111) and live birth rate per cycle initiated, 2.5% (3/111). In group II, 3 of 33 patients were cancelled. The reasons were inadequate ovarian response, risk of hyperstimulation and absence of oocytes after aspiration. In 28 patients the average number of oocytes obtained was 6.9 +/- 3.9, and the average number of embryos replaced was 2.7 +/- 1.0. Six patients conceived, and all miscarried. The pregnancy rate per cycle initiated was 6/33 (18.1%), and no live births were achieved. CONCLUSION: Although the flare-up protocol after an unsuccessful luteal phase long protocol increases the pregnancy rate per cycle slightly, the live birth rate is not improved in poor responders.

Adult↗
PubMedDate not supplied

Heterotopic pregnancy: a reevaluation.

Heterotopic pregnancies, or combined intrauterine and extrauterine pregnancies, were first reported in 1708. Traditionally, the rate of occurrence has been thought to be 1:30,000 pregnancies. It has even been said in the recent literature that an intrauterine pregnancy would rule out an ectopic pregnancy. There is good evidence that this is no longer true. The reported incidence in Western Europe and the United States is most probably 1:2600 pregnancies and much higher in certain high-risk groups. Because heterotopic pregnancy is no longer a medical curiosity, it needs to be considered in the differential diagnosis of abdominal pain in pregnancy, in the management of ectopic pregnancy, and in ovulation induction. This report presents a case encountered in a typical family practice. The literature is reviewed, and probable factors responsible for the markedly increased rate (ovulation induction and increase in ectopics in general) are addressed.

Adult↗
PubMed2000

[Chronic low dose follicle stimulating hormone step-up regimen in the treatment of polycystic ovary syndrome related anovulatory infertility with clomiphene resistance].

OBJECTIVE: To assess the efficacy and safety of chronic low-dose follicle stimulating hormone (FSH) step-up regimen in ovulation induction of polycystic ovary syndrome(PCOS) related infertile patients with clomiphene (CC) resistance. METHODS: Nine PCOS related infertile patients with CC resistance were enrolled for ovulation induction by chronic low-dose FSH step-up regimen, using urinary FSH (Metrodin) or recombinant human FSH (Gonal-F) 5 cycles respectively. Follicular development was monitored by transvaginal ultrasonography and serum estradiol (E2) measurements. RESULTS: Nine out of ten cycles ovulated, among them 5 had monofollicle development, one achieved single pregnancy. No ovarian hyperstimulation syndrome(OHSS), local or systemic side effect was seen. CONCLUSION: Chronic low-dose FSH step-up regimen is an effective and safe choice in inducing ovulation for CC-resistant PCOS infertile cases. Transvaginal ultrasonography and serum E2 measurement are equally important for appropriate dose adjustment and avoidance of cancellation or OHSS.

Anovulation↗
PubMedDate not supplied

The role of ultrasound in female infertility management.

Ultrasound became an important help for the diagnosis of infertility by demonstration of the pelvic organs, of growing ovarian follicles, of intrafollicular structures and of cyclic uterine endometrial changes. Ultrasonic particularities of ovaries and their landmarks such as the ovarian artery, are described. Average ovarian blood flow can be measured. In hormone stimulated cycles, the ultrasonic examination is repeated through ovulation, induction and even afterward. The average diameter of the growing follicle is measured. The results of more than 8000 scans allowed the deduction that ovulation induction would be successful if the preovulatory follicular diameter was between 18 and 24 mm. Where two or more follicles of that diameter are present, multiple pregnancy occurs. The risk of overstimulation can be assessed. The importance of ultrasound is even higher than estradiol because it is impossible to differentiate between one big, some medium or many small follicles with hormone assays. It is possible to see the cumulus oöphorus, but not earlier than 1-2 days before ovulation. Following successful ovulation the mature follicle appears to have a more solid than cystic make-up. Signs of a failure of ovulation are given. Cyclic changes in the histology of the endometrium are described and make it possible to predict ovulation within 12 hr. Ultrasound is an important aid in predicting the time of ovulation more accurately than the basal body temperature and faster and cheaper than hormone profiles. Ultrasound plays a role in egg collection and replacement of the embryo. The detection of ovulation is very important in the treatment of infertility. This was only possible for a longtime by hormone profile. Nowadays ultrasound is an accepted method in the diagnostic procedures of this field. It permits the visualization of the position and size of the uterus, Fallopian tubes and ovaries, the exclusion of genital anomalies and the demonstration of physiological changes of these organs during the menstrual cycle. The main points of ultrasound in the diagnosis of infertility are as follows: Demonstration of the pelvic organs (uterus, Fallopian tube, ovary) and vascular structures. Demonstration of growing ovarian follicles (Measurement of their numbers and sizes). Demonstration of intrafollicular structures (Cumulus oöphorus, Corpus luteum). Demonstration of cyclic uterine endometrial changes. Most of the results were first obtained with high-resolution compound scanners, but the new generation of real-time scanners are equally capable. Sector scanners are superior to linear-array-parallel scanners, especially for the demonstration of specific structural ch

Corpus Luteum↗
PubMed1999

Plasma immunoglobulins in patients with severe ovarian hyperstimulation syndrome.

OBJECTIVE: To assess immunoglobulin (Ig) concentrations in plasma and ascitic fluid of patients with severe ovarian hyperstimulation syndrome (OHSS). DESIGN: Controlled clinical study. SETTING: Tertiary medical center. PATIENT(S): Ten patients with severe OHSS after ovulation induction for IVF and 10 controls who had undergone similar ovulation induction and did not develop OHSS. INTERVENTION(S): Three blood samples were obtained from each OHSS patient: one at the time of hospitalization for severe OHSS, one when significant clinical improvement was evident, and one at the first follow-up visit after discharge from the hospital. Blood samples were drawn from control patients 6-8 days after ET. Ascitic fluid was obtained from all patients with OHSS by therapeutic paracentesis. MAIN OUTCOME MEASURE(S): Immunoglobulin concentrations were assayed by radial immunodiffusion. RESULT(S): Significantly lower levels of gamma-globulins, specifically IgG and IgA, were detected in the plasma of patients with severe OHSS, whereas alpha- and beta-globulin levels as well as IgM levels were not significantly different from those in controls. Both IgG and IgA levels increased as patients clinically improved. Ascitic fluid contained high IgG, moderate IgA, and negligible IgM levels. CONCLUSION: Severe OHSS is characterized by hypogammaglobulinemia, attributed to leakage of medium-molecular-weight immunoglobulins such as IgG and IgA to the peritoneal cavity.

Adult↗
PubMed1996

Discrimination between chronological and ovarian age in infertile women aged 35 years and older: predicting pregnancy using basal follicle stimulating hormone, age and number of ovulation induction/intra-uterine insemination cycles.

A marked decline in fertility rates has been demonstrated in women > 35 years of age. We have previously demonstrated the importance of basal follicle stimulating hormone (FSH) concentrations plus chronological age to predict pregnancies in women aged >/=40 years undergoing ovulation induction therapy. The purpose of the current study was to extend our previous study and determine the impact of age, basal FSH concentrations and ovulation induction/inter-uterine insemination (IUI) treatment cycles on pregnancy rates in infertile women age >/=35 years. This prospective observational study was performed at a tertiary university fertility centre. Assessments of basal hormonal status and ovulation induction protocols were performed. The main outcome measured was clinical pregnancies. A total of 770 treatment cycles in 179 women aged >/=35 years were analysed. The impact of basal FSH concentrations on treatment outcomes could be bifurcated into a favourable group (FSH </=23 mIU/ml) and a poor prognosis group (FSH >/= mIU/ml). A multivariate logistic regression model was generated which accurately predicted pregnancies. There was a high degree of correlation between predicted pregnancies and observed pregnancies (r = 0.86). We conclude that age, number of treatment cycles and the interaction term basal FSH x age are useful and significant predictors of pregnancies in patients aged >/=35 years undergoing ovulation induction/IUI therapy.

Adult↗
PubMed1981

[Single administration of a progesterone preparation during early gravidity of gilts following synchronized ovulation and induction of puberty to lower the age of first insemination].

The action of one single injection of 62.5 mg of hydroxy-progesterone-capronate on the 14th day after first insemination was tested for the purpose of defining the fertility performance of 180 gilts with synchronised ovulation and induced puberty. Synchronised ovulation caused significant rise in litter size and enhancement in gravidity rates. By comparison with a control group, the number of piglets born additional to each first insemination was 2.3. Induction of puberty to lower first-insemination age was of significant positive effect only on the pregnancy result, and somewhat fewer piglets were actually born. Nevertheless, the surplus birth figure to each first insemination was 2.1, as compared to untreated sows. The positive effect on puberty-induced animals was inversely proportional to daily weight rise.

17 alpha-Hydroxyprogesterone Caproate↗
PubMed1994

In vitro fertilization of androgen sterilized mice.

In order to explore the effect of neonatal androgen administration on oocyte quality, ovulation induction and in vitro fertilization (IVF) were performed in androgen-sterilized mice. Androgen sterilized mice were produced by the subcutaneous injection of testosterone propionate (TP) at 5 days of age and ovulation induction was performed by pregnant mare's serum gonadotropin (PMSG)-human chorionic gonadotropin (hCG) treatment at 9 to 13 weeks old. The number of oocytes ovulated in TP-injected mice was 19.9 +/- 2.0 (Mean +/- SE) and was significantly less than that in normal mice (37.8 +/- 1.9; P < 0.01). The fertilization rate of oocytes retrieved from TP-treated mice (38.8%) was significantly lower than that from normal mice (60.3%; P < 0.01). These results indicate that neonatal androgen treatment has a detrimental effect on oocyte maturity.

Animals↗
PubMed2000

Management of patients with antiphospholipid antibodies undergoing in vitro fertilization.

Infertility affects 10-15% of all married couples of reproductive age in the United States and results in substantial emotional distress and medical investment. Though it is uncertain whether antiphospholipid syndrome (APS) is a cause of infertility, inevitably there is a small proportion of women who have both APS and infertility. In turn, some of these patients are candidates for ovulation induction, with or without assisted reproductive technologies, such as in vitro fertilization and embryo transfer, in an attempt to achieve successful pregnancy. The medications used for ovulation induction cause an increase in ovarian estrogen production beyond that typical of a normal menstrual cycle. Clinicians are appropriately concerned about the potential adverse effects of this estrogen surge on the clinical status of women with autoimmune disease. For APS, a primary concern would be that of thrombosis or embolism.

Antibodies, Antiphospholipid↗
PubMed1999

Endometrial fluid collection in women with PCOS undergoing ovarian stimulation for IVF. A report of four cases.

BACKGROUND: The presence of endometrial fluid collections' developing during ovarian-stimulation was previously reported to occur in women with hydrosalpinx. We report on the occurrence of endometrial fluid collections in four women with polycystic ovary syndrome (PCOS) undergoing ovarian stimulation for in vitro fertilization. CASES: Four women developed endometrial fluid collections during ovarian stimulation. These fluid collections were noted as early as day 5 of stimulation. The reproductive outcome when fluid collections were noted on the day of human chorionic gonadotropin (hCG) or of embryo transfer (ET) was poor. One of three women with fluid collection on the day of hCG conceived but had a missed abortion. One patient with fluid on the day of ET failed to conceive. Three of four patients who underwent repeat cycles conceived when no fluid collections were seen on day of hCG or ET. CONCLUSION: Abnormal endometrial milieu could be an underlying defect in some women with PCOS and chronic anovulation who fail to conceive with ovulation-induction agents. This is the first report of endometrial fluid collections in patients with PCOS in the absence of hydrosalpinx. Continuous monitoring of the endometrial lining during ovulation induction is mandatory to rule out any abnormality in endometrial development. Cryopreserving all embryos may be considering in cycles with fluid collections noted on the day hCG or ET.

Adult↗
PubMed2001

Soluble ICAM-1 and E-selectin levels correlate with clinical and biological aspects of severe ovarian hyperstimulation syndrome.

OBJECTIVE: To assess the potential involvement of the soluble endothelial cell-leukocyte adhesion molecules E-selectin and intercellular adhesion molecule-1 (ICAM-1) in the pathophysiology of capillary hyperpermeability in the ovarian hyperstimulation syndrome (OHSS). DESIGN: Controlled clinical study. SETTING: Women hospitalized for severe OHSS after ovulation induction for IVF at two tertiary medical centers. PATIENT(S): Eleven patients with severe OHSS undergoing IVF and 20 controls who had received a similar ovulation induction regimen and did not develop OHSS. INTERVENTION(S): Serial serum samples were obtained from all patients with OHSS from admission until discharge. Ascitic fluid was obtained from all patients by therapeutic paracentesis. Serum was obtained from all controls 4-8 days after ET. MAIN OUTCOME MEASURE(S): Samples were assayed for soluble E-selectin and soluble ICAM-1 by using enzyme-linked immunosorbent assay and results were correlated with clinical and biological aspects of OHSS. RESULT(S): Compared with controls, patients with severe OHSS had higher levels of soluble ICAM-1 and lower levels of soluble E-selectin detected in serum and ascites. Serum levels of soluble ICAM-1 decreased, while soluble E-selectin levels increased along with clinical and biological improvement. Serum soluble ICAM-1 showed significant positive correlation and serum soluble E-selectin showed significant negative correlation with clinical and biological aspects of severe OHSS. CONCLUSION(S): Soluble ICAM-1 and soluble E-selectin seem to be involved in the pathophysiology of capillary hyperpermeability in severe OHSS.

Adult↗