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PubMed1998

Clomiphene citrate challenge test: cycle to cycle variability of cycle day 10 follicle stimulating hormone level.

The clomiphene citrate challenge test (CCCT), a means of assessing ovarian reserve, was shown by several studies to have an excellent predictive value for achieving conception in natural cycles, during ovulation induction and in-vitro fertilization cycles. Accordingly we elected to study the cycle to cycle variability of CCCT so as to determine the reliability of a single CCCT result. Two groups of patients were studied, the first (n = 40) were those patients who were performing the test because it was indicated, and the second (n = 24) were those who were receiving clomiphene citrate for ovulation induction. In both groups CCCT intercycle variability was significant in 75% of the cases, but this variability altered the prognostic values of the test in only 40% of the first group. In conclusion, our study showed a high percentage of intercycle variability of CCCT but further studies are needed to evaluate the influence of this variability on potential conception.

Adult↗
PubMed2003

Oncologic and reproductive outcome after fertility-saving surgery in ovarian cancer.

The rate of ovarian tumour diagnosis in reproductive age woman has increased parallel to the improvements in diagnostic methods and regular gynaecological visits. Because of this organ saving surgical procedures for the preservation of reproductive and endocrine functions have gained more interest. Conservative surgical approaches for ovarian tumours after surgical staging include cystectomy, unilateral salpingo-oophorectomy and unilateral salpingo-oophorectomy plus contralateral cystectomy. Ovarian tumours diagnosed in young ages tend to be low-stage low-grade malignancies. This not only enables but also necessitates preserving the fertility of women who have not completed their family. In invasive ovarian cancer, fertility saving surgery is confined to early-stage and low-grade disease. But, it also had been reported in advanced stages (up to Stage IIIc). Candidates for those procedures were selected according to the FIGO stage, grade, ploidy state, histological subtypes and patients' desire. Adjuvant chemotherapy is necessary for high-risk patients. The rate of recurrence following conservative and radical surgical procedures in low-stage and low-grade tumours are 9% and 11.6%, respectively; and disease-free and overall survival rates do not differ significantly. Prognosis of borderline ovarian tumours is excellent. Five and 20-year survival rates are 95% and 80%, respectively. Management of borderline tumours has evolved significantly in the last few decades. In contrast to invasive ovarian cancer, borderline tumours can be operated on conservatively at all stages. Chemotherapy is rarely prescribed even in advanced stages. Eighty percent of malignant germ cell tumours are diagnosed less than 30 years of age, and 70-75% of patients have Stage I disease. Conservative surgery is generally used in malignant germ cell tumours even in advanced stages. The relation between ovulation induction and tumour recurrence is not consistent in the literature. Spontaneous pregnancy rates following fertility saving surgery has been reported as 60-88%. Because of this over-treatment of these patients for fertility should be avoided. Briefly, fertility saving surgery can be performed safely in germ cell, borderline and early stage epithelial ovarian tumours in selected cases. Any increment in the rate of tumour recurrence following ovulation induction has not yet been demonstrated. Menstrual irregularities caused by chemotherapy are transient. The congenital malformation rate of ovarian cancer patients is slightly higher than that of the normal population, but no significant difference has been observed between patients who received or did not receive chemotherapy.

Adult↗
PubMed2002

[Gonadotropin-releasing hormone agonist stimulation test in anovulatory women]

OBJECTIVE: To evaluate the predictive value of ovarian response to the gonadotropin-releasing hormone agonist (GnRH-alpha) stimulation test (GAST) in anovulatory women during ovulation induction treatment. METHODS: Thirty-five patients entered and completed the study. Following administration of GnRH-alpha during the early follicular phase, the relationship between estradiol (E(2)) response, ovarian response and subsequent pregnancy was investigated. RESULTS: Three patterns of E(2) response were noted. Pattern A patients were hyper responders in induction treatment;their peak E(2) levels were the highest (14426.6 pmol/L) and they produced the most mature follicales (27.3 +/- 9.7 ). Thus pattern A patients had the highest risk of ovarian hyperstimulation syndrome (OHSS). (81.8 % ), cancellation cycle rate(72.7 % )and low pregnancy rate(18.2 % ). Pattern B patients had a favorable ovarian response with the highest pregnancy rate(62.5 % ). Pattern C was associated with a poor ovarian response. CONCLUSION: During ovulation induction treatment, GAST can be used to predict ovarian response of anovulatory women. This technique may enable us to design an ovarian induction protocol that would both reduce OHSS and increase pregnancy rate.

Journal Article↗
PubMed1986

Increased serum CA 125 levels during the first trimester of pregnancy.

An immunoradiometric assay for an ovarian tumor associated antigen (CA 125) has recently been developed. The CA 125 assay was reported to be fairly sensitive for ovarian cancer. However, elevated CA 125 levels were reportedly observed in 1% of healthy controls, 6% of patients with miscellaneous diseases and 29% of patients with non-gynecological cancer. Therefore, the specificity of the CA 125 assay must be evaluated before its wide clinical application. Furthermore, data on the CA 125 levels in pregnant women have not heretofore been reported. In the present study, CA 125 levels were determined in sera randomly obtained from normal, pregnant women at various weeks of pregnancy and in sera serially collected from women who achieved pregnancy after ovulation induction. When compared with the normal, non-pregnant state, CA 125 levels in pregnant women were significantly higher during the first trimester, but not during the second and third trimesters. Although CA 125 levels in women during the first trimester of pregnancy were significantly lower than those in patients with ovarian cancer, there was a considerable overlap between them. CA 125 levels were undetectable before pregnancy in all of the 8 patients who achieved pregnancy after ovulation induction. They rose during the first trimester of pregnancy in 7 of the 8 patients, and they decreased thereafter to undetectable levels by the end of the first trimester. The increased CA 125 level in the early pregnancy provides an important information for the clinical application of the CA 125 assay. Pregnancy should be ruled out when increased CA 125 levels are found in women during the childbearing years.

Antigens, Neoplasm↗
PubMed2003

Subfertility: causes, treatment and outcome.

Common causes of subfertility include ovulatory disorders, tubal disease, peritoneal adhesions, endometriosis, uterine abnormalities, abnormalities of sperm and advancing female age. Infertility is unexplained after thorough evaluation in about 5-10% of cases. Significant caveats must be attached to the interpretation of available data regarding infertility treatments. Successful ovulation induction in anovulatory women is possible for nearly all women except in cases of ovarian failure. Surgery is an option for some patients with tubal damage, adhesions, endometriosis and uterine abnormalities. Male factor infertility may be amenable to treatment of a specific cause, but is often empirical with the use of intra-uterine insemination (IUI) or in vitro fertilization (IVF). Egg donation is currently the most effective treatment available for age-related infertility when other treatments have not been successful. Couples with unexplained infertility may be effectively treated with ovulation induction plus IUI or IVF.

Anovulation↗
PubMed2004

Laparoscopic electrocautery of the ovaries versus recombinant FSH in clomiphene citrate-resistant polycystic ovary syndrome. Impact on women's health-related quality of life.

BACKGROUND: Ovulation induction with gonadotrophins is the standard treatment strategy for women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). Laparoscopic electrocautery of the ovaries is an alternative treatment modality, leading to a comparable cumulative pregnancy rate. In deciding which treatment to opt for, women's health-related quality of life (HRQoL) should be taken into account. METHODS: A total of 168 CC-resistant women with PCOS were randomly assigned to receive either the electrocautery strategy, entailing laparoscopic electrocautery of the ovaries followed by CC and recombinant FSH (rFSH) if anovulation persisted, or ovulation induction with rFSH. We assessed women's HRQoL with the standard questionnaires Short Form-36, Rotterdam Symptom Checklist and Center for Epidemiological Studies Depression Scale, administered before randomization and 2, 12 and 24 weeks thereafter. RESULTS: The intention to treat analysis revealed no significant differences between the treatment groups on any of the scales at any point during follow-up. In women without an ongoing pregnancy, those treated with rFSH showed significantly more depressive symptoms than women allocated to the electrocautery strategy, with or without CC, although differences were small. CONCLUSIONS: Overall, HRQoL was not affected in both groups. In women still under treatment, rFSH was slightly more burdensome for women's HRQoL than electrocautery with or without CC.

Clomiphene↗
PubMed2005

Epithelioid leiomyosarcoma of the ovary.

INTRODUCTION: Leiomyosarcoma of the ovary is a rare lesion usually seen in postmenopausal women. Epithelioid leiomyosarcoma of the ovary is exceptionally rare, with only one previously reported case. CASE: A 42-year-old nulliparous woman undergoing ovulation induction presented with a left adnexal mass. An exploratory laparotomy was performed. Frozen section diagnosis was read as fibrothecoma, and an oophorectomy was performed. The final diagnosis was epithelioid leiomyosarcoma of the ovary. Subsequently, a staging procedure including hysterectomy was performed with no residual disease. DISCUSSION: This is an unusual case for several reasons. Most leiomyosarcomas of the ovary have occurred in postmenopausal women and were of advanced stage at diagnosis. Our case had an epithelioid histology, occurred in a premenopausal woman, and was confined to the ovary. The fact that the patient was undergoing ovulation induction at the time of diagnosis raises the question of the risk of developing ovarian neoplasms with these medications.

Adult↗
PubMed1994

Adverse effects of fertility drugs.

Ovulation-induction agents are commonly used in the treatment of infertility in patients with or without ovulatory disturbances. These agents include clomifene, bromocriptine, gonadotrophin preparations and gonadotrophin-releasing hormone (GnRH) and its analogues. Each agent is associated with its own specific adverse effects. Although many of these adverse effects are benign and self-limited, some, in particular those effects associated with gonadotrophins, may be life-threatening. Commonly noted adverse effects encountered with the use of pharmacological agents to treat infertility include the following. Clomifene has been associated with hot flushes, multiple gestation, visual disturbances, cervical mucus abnormalities and luteal phase deficiency. Similarly, most of the adverse symptoms associated with bromocriptine are short-lived, such as nausea and postural hypotension. On the other hand, gonadotrophin therapy, even when used appropriately, may lead to the ovarian hyperstimulation syndrome (which is occasionally life-threatening) and a high incidence of multiple gestation. Pulsatile GnRH therapy maybe accompanied by similar adverse effects to those of gonadotrophins, but with a far lower incidence. With regards to the long term safety of these medications, the relationship between fertility drugs and epithelial ovarian cancer is controversial, and causality has yet to be proven. Indeed, a working knowledge of the many adverse effects associated with these medications is essential to any physician prescribing ovulation induction agents, in order to ensure maximum patient safety, compliance and understanding.

Bromocriptine↗
PubMed2004

Assisted reproductive technology : experience with IVF/ICSI.

OBJECTIVE: To analyze success rates of assisted reproduction techniques ART (IVF/ICSI) in couples experiencing subfertility, and factors which may help in predicting treatment outcome. DESIGN: A prospective cohort follow-up study. PLACE AND DURATION OF STUDY: Study was conducted at Concept Fertility Centre, Karachi, between July 1, 2000 and December 31, 2002. SUBJECTS AND METHODS: A cohort of 310 couples undergoing 330 in-vitro fertilization (IVF) and intra cytoplasmic sperm injection (ICSI) cycles were followed for treatment outcomes. Predictor variables included age of women, cause of subfertility, drug regimen used for ovulation induction, day of embryo transfer, and ease of embryo transfer. While outcome variables included rates of fertilization, pregnancy, live birth, miscarriages, multiple pregnancies and ovarian hyperstimulation syndrome (OHSS). RESULTS: The overall pregnancy rate was 35.2 %, while takehome live-birth rate was 25.1%. Treatment cycles which were done for male factor only, had higher probability of success as compared to female factors or for unexplained infertility. Patients who underwent transvaginal ovum pick up and embryo transfer (TVOPU + ET) had an overall pregnancy rate of 29.4% as compared to those who underwent frozen embryo transfer (FET) cycles (22.6%). There was no statistically significant difference between pregnancy rates for ovulation induction with recumbent FSH (rFSH) and HMG (32.7% v 33.6%, p-value 0.87). Quality of embryo transfer was significantly better (33.7%, v 24.2%, p-value 0.042) in patients who conceived. CONCLUSION: Our results are comparable in terms of pregnancy rates, live birth rates and complication rates, to the results reported in international literature. We however, need more data from centres in Pakistan for future reference and research.

Adult↗
PubMed2002

Medical management of pituitary adenomas: the special case of management of the pregnant woman.

The development of efficacious surgical and medical therapies for pituitary adenomas as well as the improvement of hormone therapy for ovulation induction has made pregnancy possible for women harboring pituitary tumors. However, gestational risks due to the possibility of tumor growth during pregnancy, mainly in women with macroadenomas, raise a concern. Bromocriptine has a well-established role for prolactinoma treatment before and during pregnancy, even when a symptomatic tumor increase occurs. It can also be used in acromegaly, despite its poorer results. Somatostatin analogs have been used in acromegaly even during pregnancy with uneventful outcomes, but their safety in pregnancy is not well established, yet. The largest experience with medical treatment for Cushing's disease during pregnancy involves metyrapone, a steroidogenesis inhibitor, without descriptions of congenital abnormalities. Concerning clinically non-functioning pituitary tumors, ovulation induction or even in vitro fertilization are frequently needed. The purpose of this review is to provide an update on therapeutic strategies to restore fertility as well as gestational and post-gestational management of patients with pituitary adenomas, focusing mainly on the role of medical treatment for different tumor types.

Acromegaly↗
PubMed1994

Clomiphene citrate and pregnancy outcome.

Data from Australia and elsewhere have shown consistently that adverse perinatal outcomes such as preterm birth and perinatal mortality are more common in pregnancies resulting from assisted conception with IVF and GIFT than normally conceived pregnancies. Factors that may contribute to the excess of poor outcomes include maternal factors, the assisted conception procedures themselves and possibly the influence of drugs used to induce superovulation. This review examines the medical literature describing pregnancies following ovulation induction with one of the drugs used to induce superovulation, clomiphene citrate, and compares their outcomes with Australian IVF and GIFT pregnancy outcomes. The review shows that whilst some studies have suggested higher rates of ectopic pregnancy, spontaneous abortion and congenital malformations in clomiphene citrate induced pregnancies, the findings are inconsistent and the data are flawed. There are only very poor data available on the incidence of preterm birth. Multiple pregnancy is a well-recognized adverse outcome of clomiphene citrate induced pregnancies. Attempts to improve perinatal outcomes of pregnancies following assisted conception will be helped by a better understanding of the relative contributions of maternal and treatment factors and further studies of pregnancy outcome after ovulation induction are needed.

Abortion, Spontaneous↗
PubMed1995

Follicular volume and number during in-vitro fertilization: association with oocyte developmental capacity and pregnancy rate.

This study examined the effect of the number of follicles aspirated during egg retrieval on pregnancy likelihood during an ovulation induction, in-vitro fertilization (IVF) programme. In addition, the volume of each individual follicle was related to the probability of obtaining an oocyte from that follicle. Its capacity to be fertilized, the incidence of polyspermic fertilization, the quality of early embryos derived from that oocyte and the influence of patient age were the other outcomes studied. Large follicular number and high mean follicular volume related positively to pregnancy outcome. Successful egg retrieval, normal fertilization and good embryo quality were more likely with increasing individual follicular volume. A model was constructed to quantify the predictive value of follicular fluid volume on the developmental potential of individual oocytes and embryos derived from that follicle. Successful outcome of IVF is more likely if ovulation induction results in many follicles, particularly if they have a high mean volume. Individual oocyte and embryo quality can be traced back to the follicular level.

Adult↗
PubMed2003

Thrombophilias and gynaecology.

In gynaecology, women are exposed to sex steroids when using oral contraceptives, hormone replacement therapy or when undergoing in vitro fertilization treatment and ovulation induction. Oral contraceptives and the use of hormone replacement therapy increase the risk of venous thrombosis. The risk is highest in the first year of use and higher among women with clotting defects. Women taking third-generation oral contraceptives have an almost twofold increased risk of venous thrombosis compared with those taking second-generation oral contraceptives. Inherited clotting defects, which are themselves risk factors of venous thrombosis, (e.g. factor V Leiden mutation, deficiency of protein C, protein S or antithrombin, high plasma levels of factor VIII, and prothrombin mutation) appear synergistically increase the risk of venous thrombosis caused by oral contraceptives. Recent studies also point to an interaction between hormone replacement therapy and coagulation defects in causing venous thrombosis. Emerging studies show that in vitro fertilization treatment and ovulation induction are also risk factors for venous thrombosis; the role of coagulation defects in this association is not yet clear.

Contraceptives, Oral, Hormonal↗
PubMed1996

The addition of a glucocorticoid to the protocol of programmed oocyte retrieval for in-vitro fertilization--a randomized study.

A group of 78 infertile women, diagnosed as having tubal factor infertility only, was enrolled in a prospective, randomized study conducted to determine whether the addition of different doses of glucocorticoids to the protocol of ovulation induction for in-vitro fertilization (IVF) would be beneficial. Oocyte numbers, percentage of fertilization, oestradiol, luteinizing hormone and follicle stimulating hormone serum concentrations, number of embryo transfers and pregnancy rate were evaluated. Compared to control cycles (group A; n = 24), the addition of 0.5 mg (group B; n = 27) of 1 mg dexamethasone (group C; n = 27), combined with the protocol of programmed oocyte retrieval for IVF patients in the study, demonstrated equivalent results. The mean numbers of oocytes retrieved were 10.8 +/- 3.9 in the control group, compared to 11.2 +/- 4.0 in group B and 10.5 +/- 3.6 in group C. The fertilization rates were 69 +/- 21, 66 +/- 18 and 70 +/- 15% respectively. The pregnancy rates were 20, 16 and 20.8% respectively. The addition of up to 1 mg dexamethasone daily to the protocol of ovulation induction for oocyte retrieval did not improve the overall IVF-embryo transfer outcome in patients with tubal factor infertility.

Adult↗
PubMedDate not supplied

Achieving and maintaining pregnancy after age 40.

Demographic data from the United States show the need for testing ovarian reserve in a population that is increasingly delaying reproduction. The childless rate for U.S. women over the age of 35 has nearly doubled to 25% since 1925. Yet, in 1994 approximately one-third of all first births were by women over the age of 35. The first-line treatment for the aging effect on the ovarian reservoir of oocytes is ovulation induction. Study results reveal that a delivery rate of only 2.4% was achieved at age 42, and in 119 cycles of therapy in women above that age there were no live births. The clomiphene citrate challenge test is one method of dynamic testing of ovarian reserve. It has the advantages of simplicity and reduced cost when compared with the gonadotropic stimulatory test. In one test group utilizing the clomiphene citrate challenge test only 4.8% conceived at any age following an abnormal test. As a prognostic test with an approximate 95% accuracy rate for negative predictive value it has much to offer. With oocyte donation becoming more widespread as an acceptable method of achieving pregnancy, clomiphene citrate challenge testing should be performed more frequently, in order to spare couples the emotional and financial sequelae of multiple attempts at ovulation induction and IVF when expected pregnancy rates fall below a level acceptable to both patient and physician.

Adult↗
PubMed1994

Expression of functional human chorionic gonadotropin/human luteinizing hormone receptor gene in human uterine arteries.

The present study investigated 1) whether extra- and intramyometrial arteries contain hCG/human LH receptor messenger ribonucleic acid (mRNA) and receptor protein, 2) whether hCG can bind to its vascular receptors and regulate the formation of vasoactive eicosanoids, and 3) whether hCG administration for ovulation induction can affect the vascular resistance in uterine arteries. The uterine arteries contain multiple hCG/LH receptor mRNA transcripts in endothelial and smooth muscle cells. The uterine arteries also contain an 80-kilodalton immunoreactive receptor protein in endothelial and smooth muscle cells. The extra- and intramyometrial arteries and an 80-kilodalton receptor protein bind [125I]hCG, which is inhibited by excess unlabeled hCG. The receptor mRNA, receptor protein, and ligand binding are higher in smaller intramyometrial arteries than in larger extramyometrial arteries. Incubation of uterine arteries with highly purified hCG resulted in a dose-dependent increase in immunoreactive cyclooxygenase-1, cyclooxygenase-2, prostacyclin synthase, and 6-keto-prostaglandin-F1 alpha and a decrease in prostaglandin-E2, thromboxane-A2 synthase, and thromboxane-B2. There was a significant decrease in the resistance index in uterine arteries, but not in common carotid arteries, by 16 h after the administration of 10,000 IU hCG for ovulation induction in women. This decrease is positively correlated with serum hCG levels, but not with progesterone or estradiol levels. In summary, these data, demonstrating the expression of functional hCG/LH receptors in human uterine arteries, are novel and may have important implications for physiological uterine blood flow regulation, reproductive failure, and obstetrical hemorrhage.

Adult↗
PubMed1990

Luteal rescue in in vitro fertilization-embryo transfer.

The luteal phase hormone profiles of two groups participating in the Yale in vitro fertilization (IVF) program were compared. A control group (group I) consisted of 28 women (28 cycles) who received our standard ovulation induction regimen (no luteal phase support). The treatment group (group II) consisted of 40 women (42 cycles) who were prospectively studied after receiving luteal phase support with 10,000 IU human chorionic gonadotropin (hCG) 5 days after the initial hCG dose. The groups were matched for age and cause of infertility. Estradiol (E2) and progesterone (P) were measured on the day of embryo transfer and every 3 to 4 days thereafter. Luteal phase hCG support significantly augmented (1) E2 and P levels in the conception cycles of group II compared with group I and (2) P levels in the nonconception cycles of group II compared with group I. The midluteal decline in E2 and P that was observed in group I was minimized or prevented in group II. An ongoing pregnancy rate of 19% was achieved in group II. This was not statistically different from the 13% ongoing pregnancy rate noted in a separate group of 163 tubal factor couples undergoing IVF after our standard ovulation induction regimen during the period of the study. In summary, the luteal phase hormone profiles of IVF cycles were improved by supplementation with hCG. It is concluded that this type of intervention may serve to rescue potentially failing corpora lutea and thereby optimize the peri-implantation hormonal milieu.

Adult↗
PubMed1987

Clomiphene citrate augments follicle-stimulating hormone-induced luteinizing hormone receptor content in cultured rat granulosa cells.

Although clomiphene citrate (CC) has been widely used for ovulation induction, the mechanism of its pro-fertility effect is not entirely clear. Because CC augments ovarian aromatase activity, the effect of CC on follicle-stimulating hormone (FSH)-induced luteinizing hormone (LH) receptor content was examined in primary cultures of rat granulosa cells. Control cultures contained low LH receptor content, whereas FSH stimulated LH receptor formation in a dose-dependent manner. The concomitant addition of CC enhanced FSH potency as shown by a decrease in the ED50 for FSH by 2.2-fold. Some cells were treated with a low concentration of FSH (12 ng/ml) in the presence or absence of increasing concentrations of CC (10(-8) M to 10(-6) M). The enhancement of FSH-stimulated LH receptor formation was found to be CC dose dependent, with an ED50 of 6 X 10(-8) M. Thus, CC may play a direct ovarian role in the enhancement of FSH-stimulated LH receptors. The gonadal action of this compound may be relevant in understanding the efficacy of CC in ovulation induction.

Animals↗