Use Of Ovarian Stimulation Research Articles

Fertility Preservation and Assisted Reproduction in Patients With Breast Cancer Interrupting Adjuvant Endocrine Therapy to Attempt Pregnancy.

We investigated time to pregnancy, efficacy and safety of fertility preservation, and assisted reproductive technologies (ARTs) in women with early hormone receptor-positive breast cancer (BC) desiring future pregnancy. POSITIVE is an international, single-arm, prospective trial, in which 518 women temporarily interrupted adjuvant endocrine therapy to attempt pregnancy. We evaluated menstruation recovery and factors associated with time to pregnancy and investigated if ART use was associated with achieving pregnancy. The cumulative incidence of BC-free interval (BCFI) events was estimated according to the use of ovarian stimulation at diagnosis. The median follow-up was 41 months. Two hundred seventy-three patients (53%) reported amenorrhea at enrollment, of whom 94% resumed menses within 12 months. Among 497 patients evaluable for pregnancy, 368 (74%) reported at least one pregnancy. Young age was the main factor associated with shorter time to pregnancy with cumulative incidences of pregnancy by 1 year of 63.5%, 54.3%, and 37.7% for patients age <35, 35-39, and 40-42 years, respectively. One hundred and seventy-nine patients (36%) had embryo/oocyte cryopreservation at diagnosis, of whom 68 reported embryo transfer after enrollment. Cryopreserved embryo transfer was the only ART associated with higher chance of pregnancy (odds ratio, 2.41 [95% CI, 1.75 to 4.95]). The cumulative incidence of BCFI events at 3 years was similar for women who underwent ovarian stimulation for cryopreservation at diagnosis, 9.7% (95% CI, 6.0 to 15.4), compared with those who did not, 8.7% (95% CI, 6.0 to 12.5). In POSITIVE, fertility preservation using ovarian stimulation was not associated with short-term detrimental impact on cancer prognosis. Pregnancy rates were highest among those who underwent embryo/oocyte cryopreservation followed by embryo transfer.

Disease-free survival does not differ according to fertility preservation technique for young women with breast cancer

To study whether fertility preservation strategies using ovarian stimulation or without using it impact long-term disease-free survival of patients with breast cancer. Retrospective bicentric cohort study. Two university hospitals. In this study, 740 women with breast cancer, aged 18-43 years, who received primary fertility preservation between 2013 and 2019 after a diagnosis of localized breast cancer were included. Overall, 328 patients underwent at least 1 ovarian stimulation cycle (STIM group) and 412 had a technique without hormonal administration (no STIM group). Disease-free survival and overall survival up to May 2021 were compared between the 2 groups by log-rank test. Cox proportional-hazard regression model was used for multivariable analyses. Out of the 740 women who underwent fertility preservation, follow-up data were available for 269 women in the STIM group (82%) and 330 (80%) in the no STIM group. Kaplan-Meier estimates of disease-free survival at 4 years were 87.9% (82.8%-92.2%) and 83.1% (78.4%-87.3%) in the STIM and no STIM groups, respectively. After adjustment on prognostic parameters, no significant difference in breast cancer recurrence rate was observed between the STIM and no STIM groups (hazard ratios, 0.83 [0.64-1.08]). Kaplan-Meier estimate of overall survival at 4 years was 97.6% (95.3%-99.2%) and 93.6% (90.9%-95.9%) in the STIM and no STIM groups, respectively. Overall survival was higher in the STIM group than no STIM group (log-rank test). After adjustment on prognostic parameters, the risk of death remained significantly lower in the STIM group (Hazard Ratio, 0.55 [0.35-0.85]). In our cohort, STIM for fertility preservation in breast cancer did not significantly impact disease-free survival but was associated with higher overall survival. The disease-free survival and overall survival of young patients with breast cancer were not impacted by fertility preservation techniques irrespective of the timing of chemotherapy (neoadjuvant or adjuvant) and the use of ovarian stimulation. Nevertheless, because death and recurrence were rare events, these results should be taken with caution.

O-195 Disease-free survival is not impacted by fertility preservation techniques for breast cancer women

Abstract Study question Do fertility preservation (FP) strategies using ovarian stimulation or not, impact long-term disease-free survival of breast cancer (BC) patients? Summary answer The disease-free survival of BC patients is not impacted by FP techniques whatever the timing of chemotherapy (neoadjuvant /adjuvant) and the use of ovarian stimulation. What is known already Fertility is often impaired in young women treated for BC. Therefore, FP has become a major issue in this population. Cryopreservation of oocytes or embryos after controlled ovarian hyperstimulation (COH) represents the most established method in this clinical situation. However, the hormonal consequences of COH protocols still raise safety concerns, often leading oncologists to contraindicate the use of this FP technique. Although alternative FP options without exogenous hormone administration may be considered, they remain suboptimal for treating the putative future infertility. Study design, size, duration Retrospective bicentric cohort study including including 740 BC women, 18-43 years of age, referred for FP between 2013 and 2019. Participants/materials, setting, methods Overall, 328 underwent at least one ovarian stimulation cycle (STIM group) and 412 had a technique without hormonal administration (No STIM group). Log Rank test was used to compare both groups and Cox proportional-hazard model was applied for multivariable analyses. Main results and the role of chance Women of the No STIM group were significantly younger and present with more severe disease. Follow-up data for recurrences were available for 80.9% of the cohort and the median time to follow-up was 4.2 [2.9-5.8] vs. 5.6 [4.1-6.7] years between STIM and No STIM group (p &amp;lt; 0.0001). According to log-rank test, the risk of recurrence did not differ between the two groups (p = 0.09) even after adjustment on age, SBR grade, triple negative status or type of planned chemotherapy. Limitations, reasons for caution The retrospective nature of the study represents the main limitation. The median follow-up of 4.2 to 5.6 years, might be considered short to assess the long-term safety of FP techniques. The heterogeneity between oncological centers regarding the use of COH and specific protocols may lalso be a reason for caution. Wider implications of the findings Our findings provide reassuring safety data on the use COH for FP in BC patients, whatever the timing of chemotherapy. However, further investigations with a longer follow-up are needed to definitely consider COH safe in particular in neoadjuvant situations. In addition, the benefit of letrozole supplementation during COH requires confirmation. Trial registration number Not applicable

Is intrauterine insemination a viable treatment option for women over 43years old? An analysis by ovarian stimulation protocol and sperm source.

The aim of this study was to determine how female age at the end of the reproductive spectrum effects success of natural cycle intrauterine insemination (IUI) or IUI in combination with ovarian stimulation. We performed a retrospective cohort study of women 43years of age and older at the time of IUI in a single academic fertility center between January 2011 and March 2018. Primary outcomes were both pregnancies and live births per cycle of IUI. Data are presented as percentage or mean ± SD. Fisher exact and chi-squared analyses were performed. There were 9334 IUI cycles conducted during the study period. Of these cycles, 325 IUIs (3.5%) were for women aged 43years and over at the time of insemination (43.6 ± 0.8, range 43 to 47years). Analysis of these 325 IUI cycles revealed 5 biochemical pregnancies (1.5%) and only 1 live birth (0.3%). The pregnancy rate did not differ between IUIs using donor sperm (N = 1/49, 2.0%) compared to IUIs with partner sperm (N = 4/276, 1.4%). The pregnancy rate did not differ between IUIs with gonadotropins (N = 2/211, 0.9%), clomiphene or letrozole (N = 2/78, 2.6%), or natural cycle (N = 1/36, 2.8%). The use of intrauterine inseminations in women 43years of age and older is an ineffective treatment strategy. This is irrespective of the use of ovarian stimulation or donor sperm. Costly gonadotropin injections did not increase the chance of pregnancy nor did oral medication when compared to natural cycle IUIs.

Successful Laparoscopic Diagnosis and Management of Bilateral Tubal Pregnancy: Description of a Case and Review of the Literature

Background: Bilateral tubal pregnancy is extremely rare, but, today, the incidence has increased because of the common use of ovarian stimulation and in vitro fertilization (IVF). This article reports a case of a contralateral small tubal pregnancy together with a ruptured tubal pregnancy and describes how laparoscopy assisted in this diagnosis. Case: A 28-year-old woman presented with vaginal bleeding and right-sided abdominal pain. She had undergone IVF and transfer of 2 embryos 4 weeks prior. Her serum β-human chorionic gonadotropin (β-hCG) level was 12,889 mIU/mL. Results: A diagnostic laparoscopy was performed. The patient was diagnosed with a ruptured right tubal pregnancy and a salpingectomy was performed. In addition, a small distension of the left tube was found and a left salpingectomy was performed. Pathologic examination identified chorionic villi in both fallopian tubes. The patient's postoperative course was uneventful. Conclusions: This case report highlights that clinicians need to be aware of such rare and potentially fatal conditions after IVF, and that repeated transvaginal ultrasound and hCG assays are mandatory.

Predictive factors influencing pregnancy rates after intrauterine insemination with frozen donor semen: a prospective cohort study

The extent to which certain parameters can influence pregnancy rates after intrauterine insemination with frozen donor semen was examined prospectively. Between July 2011 and September 2015, 402 women received 1264 IUI cycles with frozen donor semen in a tertiary referral infertility centre. A case report form was used to collect data prospectively. The primary outcome measure was clinical pregnancy rate (CPR), confirmed by detection of a gestational sac and fetal heartbeat using ultrasonography at 7–8 weeks of gestation. Statistical analysis was carried out using generalized estimating equations (GEE) to account for the correlation between observations from the same patient. Overall, CPR per cycle was 17.2%. Multivariate GEE analysis revealed the following parameters as predictive for a successful pregnancy outcome: female age (P = 0.0003), non-smoking or smoking fewer than 15 cigarettes a day (P = 0.0470 and P = 0.0235, respectively), secondary infertility (P = 0.0062), low progesterone levels at day zero of the cycle (P = 0.0164) and use of ovarian stimulation with HMG and recombinant FSH compared with clomiphene citrate and natural cycle (P = 0.0006 and P = 0.0004, respectively). These parameters were the most important factors influencing the success rate in a sperm donation programme.

Risk of Colorectal Cancer After Ovarian Stimulation for In Vitro Fertilization.

Apart from lifestyle factors, sex hormones also seem to have a role in the etiology of colorectal cancer. This raises interest in the possible effects of fertility drugs, especially because the use of ovarian stimulation for in vitro fertilization (IVF) has strongly increased over the past decades. In 1996, a nationwide cohort study was set up to examine cancer risk in a population that included 19,158 women who received ovarian stimulation for IVF (IVF group) and 5950 women who underwent subfertility treatments other than IVF (non-IVF group). Cancer incidence was ascertained through linkage with the Netherlands Cancer Registry. Colorectal cancer risk in the IVF group was compared with those in the general population and in the non-IVF group. After a median follow-up of 21 years, 109 colorectal cancers were observed. Compared with the general population, risk of colorectal cancer was not increased in the IVF group (standardized incidence ratio, 1.00; 95% confidence interval [CI], 0.80-1.23), and was significantly decreased in the non-IVF group (standardized incidence ratio, 0.58; 95% CI, 0.36-0.88). Women in the IVF group had a significant increase in risk compared with women in the non-IVF group (multivariable-adjusted hazard ratio, 1.80; 95% CI, 1.10-2.94). No trend emerged with more IVF cycles or more ampules of gonadotropins administered. Colorectal cancer risk did not increase with longer follow-up periods. Although women who receive ovarian stimulation for IVF do not have an increased risk for colorectal cancer compared with the general population, findings from our nationwide cohort study indicate that their risk is increased compared with women who received subfertility treatments other than IVF. Further research is warranted to examine whether ovarian stimulation for IVF contributes to development of colorectal cancer.

Uterine Artery Embolization for a Safe Surgical Abortion in Human Very High-Order Multifetal Pregnancy: A Case Report

In the last few decades, the use of ovarian stimulation with follicle stimulating hormone (FSH) or clomiphene citrate (CC) increases the percentage of multiple pregnancies. The presence of many follicles can lead to the risk of higher-order multiple pregnancy and ovarian high stimulation syndrome (OHSS). This is correlated to a significant increase in morbidity and mortality maternal and/or fetal rate. For this reason, sometime therapeutic measures are necessary to preserve woman’s health. We describe the case of a surgical abortion using a transcatheter arterial embolization (TAE), a minimally invasive, safe and effective procedure to preserve the patients.

Laparoscopic Surgery for Heterotopic Pregnancies: Two Cases

Background: Heterotopic pregnancy is a rare clinical condition, but it is increasingly being diagnosed after the common use of ovarian stimulation and the advent of assisted reproductive techniques. Two cases of heterotopic pregnancy, successful laparoscopic removal of one ectopic pregnancy, and a subsequent favorable outcome of the intrauterine pregnancy, are presented. Cases: The first case was associated with ovarian hyperstimulation syndrome following in vitro fertilization and embryo transfer, and the second case occurred after intrauterine insemination. Results: Via laparoscopy, both cases were diagnosed with ruptured tubal ectopic pregnancy, and laparoscopic salpingectomy after evacuation of the hemoperitoneum was performed. The first patient, at 39 and 1/7 weeks of gestation, was delivered of healthy newborn, weighing 3910 g. In the second patient, at 9 and 4/7 weeks of gestation, an ultrasound scan confirmed a viable intrauterine pregnancy. Since then, the patient has been lost to follow-up. Conclusions: Laparoscopy allows for both a differential diagnosis in an uncertain condition during pregnancy, and a favorable outcome of an intrauterine pregnancy. In the light of this, laparoscopy may be the treatment of choice for patients with heterotopic pregnancies. (J GYNECOL SURG 30:305)

Multiple Pregnancies After ART and How to Minimize their Occurrence

In the past few decades, the number of multiple pregnancies has increased significantly. Advanced maternal age, use of ovarian stimulation and use of IVF are all responsible for this. A multiple pregnancy carries excess maternal and neonatal risks and is associated with undesired extra health care expenses as well. Up to 1/3 of the pregnancies following IVF are multiple gestations; most being twins. The best way to minimize the risk of twins is to transfer a single embryo only. The majority of the embryos do not implant however and most clinics routinely transfer 2 or even more embryos to maintain high IVF success rates (pregnancy rates). A high success rate despite the transfer of fewer, preferably a single embryo could be maintained if we had better tools to identify the embryo with the highest implantation potential. Current selection criteria based on the cleavage rate and morphology of the embryo are not particularly effective for this. The past decade has seen a lot of research aiming to screen the embryos based on various properties. This review will discuss the perinatal outcome of IVF multiples, available screening tools for embryo selection and the current status of the development of new tools.

An integrated view on the luteal phase: diagnosis and treatment in subfertility

The term 'luteal phase deficiency' was first coined more than 60 years ago, and, since then, it has been suggested as a clinical entity per se and an aetiological factor for subfertility, implantation failure and recurrent miscarriage. Despite the existing recommendations for rational work-up in subfertility, luteal phase evaluation and progesterone therapy alone is still common in daily practice. This review comprises results from a Pubmed literature search with the terms 'luteal phase' and 'subfertility', focussing on clinical situations not primarily related to assisted reproduction techniques. Additional data from the experimental studies published in the past 10 years on follicular maturation, oocyte developmental competence and the ovulatory cascade are integrated into the clinical continuum of dysfunctional ovulation, menstrual cycle irregularity and impaired corpus luteum function. As reliable diagnostic tools for adequate luteal function are missing, the presence of clinical symptoms such as cycle irregularity or premenstrual spotting is indicative and should initiate early follicular phase diagnostic work-up. New evidence on the interdependence of oocyte and follicular maturation and resulting developmental competence of the embryo further support the use of ovarian stimulation as the first-line therapeutic option in different subsets of patients with subfertility including luteal phase deficiency.

Hormonal and molecular characterization of follicular fluid, cumulus cells and oocytes from pre-ovulatory follicles in stimulated and unstimulated cycles

The use of ovarian stimulation, to stimulate a multi-follicular response for assisted reproduction treatments, may force the production of oocytes from follicles that do not reach optimal maturation, possibly yielding oocytes that are not fully competent. The present study aimed to define the follicular environment and oocyte competence of unstimulated pre-ovulatory follicles, to compare it with that of similar-sized stimulated follicles. For this purpose, we analyzed the follicular hormonal milieu, the oocyte meiotic spindle, the embryo development and the cumulus cells gene expression (GE) profiles. The study population was divided in two groups: (i) 42 oocyte donors undergoing unstimulated cycles and (ii) 18 oocyte donors undergoing controlled ovarian stimulation cycles (COS). Follicular fluid was analyzed to quantify the concentrations of estradiol (E2), progesterone (P), FSH, LH, testosterone (T) and androstendione (Δ4). T was higher in the COS group, while Δ4, E2 and LH were significantly higher in unstimulated cycles. The cumulus oophorus cells (CC) surrounding the oocyte were removed and their GE profiles were analyzed with microarrays. There were 18 differentially expressed genes in CC: 7 were up-regulated and 11 were down-regulated in the COS cycles. The microarray was validated by qRT-PCR. The analysis of spindle structure revealed no significant differences between the groups, except for the parameter of length which presented differences. The fertilization ability and embryo morphology on Days 2, 3 and 4 did not show any significant differences between groups. The use of ovarian stimulation induces changes in the follicular fluid and in CC GE that may affect immune processes, meiosis and ovulation pathways. Although these differences do not seem to relate to early-stage embryo morphology, the implications of some of the molecules, especially ALDH1A2, CTSL and ZNF33B at the CC level, deserve to be addressed in future studies.

Aromatase inhibitors for ovulation induction and ovarian stimulation

Aromatase inhibitors (AIs) were originally developed for the treatment of advanced breast cancer in postmenopausal women. Their use in reproductive medicine has been extensively studied in the past decade. We reviewed the current strategies for ovulation induction for anovulatory women, mostly women with polycystic ovarian syndrome (PCOS), and the scientific basis for use of AIs in reproductive medicine. The AI, letrozole, is effective in ovulation induction in women with PCOS resistant to clomifene citrate and ovarian stimulation for intrauterine insemination and in vitro fertilization (IVF). Letrozole is an attractive option with its oral route of administration, cost, safety profile and effectiveness in ovulation induction and ovarian stimulation. Letrozole has the potential to be the first-line treatment option for ovulation induction in PCOS women, while its use in ovarian stimulation for IVF deserves further study.

Recombinant human follicular stimulating hormone and recombinant human luteinizing hormone in a 2:1 ratio combination. Pharmacological characteristics and clinical applications

Importance of the field: A new fixed combination of recombinant human follicle stimulating hormone (r-hFSH) and recombinant human luteinizing hormone (r-hLH) at a 2:1 ratio has been recently developed to induce ovulation in patients with hypogonadotrophic hypogonadism. Whether or not this compound is useful for controlled ovarian stimulation for in vitro fertilization is still a matter of debate.Areas covered in this review: Description of pharmacological and clinical aspects of this new product, through the analysis of the Phase I, II and II trials and post-marketing clinical randomized trials, performed since the initial assays in 1998 to nowadays.What the reader will gain: After reading this review the reader will understand the pharmacological aspects of this new compound, in terms of efficacy and safety, and will have an update of the potential role of r-LH administration in controlled ovarian stimulation for in vitro fertilization.Take home message: The 2:1 combination of r-hFSH and r-hLH has been seen as an optimum preparation in terms of safety and clinical efficacy in hypogonatrophic hypogonadism patients. Its use in ovarian stimulation for IVF remains controversial, as the target population that may receive a benefit of it is not well defined.

Focus on Breast and Ovarian Cancer

In reproductive medicine the widespread use of ovarian stimulation has focused interest on the possible relation between induction of ovulation and breast and ovarian cancer. The epidemiological studies published so far are reassuring but not devoid of methodological problems, such as small populations, short follow-ups, and lack of information on confounding factors like oral contraceptive use. In younger patients to preserve fertility before radio- or chemotherapy, the American Society of Clinical Oncology recommended embryo cryopreservation as an established procedure. Moreover, experimental procedure as oocytes cryopreservation, ovarian suppression with GnRH analogues and cortical ovarian tissue freezing probably will be routinely used in the future. A reasonable proposal to protect patients from the risk of estrogen peaks in the case of estrogen receptor positive (ER+) breast cancer, ovarian stimulation with tamoxifen or letrozole could be right. Powered studies are necessary to control the safety and effectiveness of the different fertility preservation options. In this review we evaluated the relation between induction of ovulation and breast and ovarian cancer and then the possible options for fertility preservation in patients with these types of tumors.

P-518: Effect of LBFS0101, a new recombinant follicle-stimulating hormone, in human in vitro fertilization and embryo transfer program: A prospective and randomized clinical study

The purpose of this study was to analyze the efficacy and tolerability of follitropin-heterodimeric alpha-beta subunit mixture (LBFS0101; LG Life Sciences Ltd., Seoul, South Korea), new recombinant human FSH (r-hFSH) preparations, for superovulation in patients undergoing IVF-ET. Randomized, parallel-group, open, multi-center clinical study. One hundred and three infertile women undergoing IVF-ET in 2005 were entered into the study under approval of the Institutional Reviewer Board. After down-regulation with buserelin acetate, patients were randomized to receive LBFS0101 (n=52) or Gonal-F (Serono Inc., Geneva, Switzerland, n=51). r-hFSH was administrated at 150-300 IU/d for 3∼5 days, and then dosages were adjusted according to the ovarian response. Ovarian stimulation characteristics, ovum retrieval, and IVF/ICSI outcomes were compared. Total of 15 cycles were cancelled, 88 cycles (LBFS0101 = 47 cycles; Gonal F = 41 cycles) were studied. There were no statistically significant differences in any clinical profiles of patients between the two preparations. Also, cumulative dose of r-hFSH (2371.3 ± 728.4 mIU for LBFS0101 vs.2409.8 ± 769.4 mIU for Gonal F), duration of r-hFSH treatment (9.3 ± 2.0 days vs. 9.3 ± 1.8 days), number of follicles of ≥ 14 mm on the of hCG injection (9.3 ± 4.6 days vs. 10.6 ± 5.8), and number of retrieved oocytes (14.2 ± 9.1 vs. 14.4 ± 8.8) were not different. Clinical pregnancy rate and implantation rates were similar (44.7% (21/47), 22.1% (38/169) for LBFS0101 and 56.1% (23/41), 29.5% (41/139) for Gonal F). Anti-FSH antibody was not detected in all samples. The results of this clinical study indicate that LBFS0101 may be suitable for use in ovarian stimulation for human IVF-ET program.

Maternal Drug Use, Fertility Problems, and Infant Craniostenosis

To test the hypothesis that maternal drug use or treatment for infertility is related to the occurrence of infant craniostenosis. Maternal drug use and infertility treatment were studied in 398 cases of craniostenosis, identified from various Swedish health registers. Exposure information was ascertained in early pregnancy, and comparisons after adjustment for some confounders were made with all infants born. In order to validate some findings, data from the Central-East France Registry were studied for first trimester drug exposure in 235 infants, and use of ovarian stimulation in 315 infants with craniostenosis. A statistically significant association between maternal use of anticonvulsants and infant craniostenosis was found (risk ratio [Swedish data], 6.9; 95% confidence interval, 1.10 to 7.94). With the Swedish data, an association was found with three nitrosatable drugs (risk ratio, 3.4; 95% confidence interval, 1.10 to 7.94), previously associated with the occurrence of craniostenosis, but this was based on only five exposures, and no such exposure occurred in the French data set. No association with subfertility (odds ratio, 0.72; 95% confidence interval, 0.60 to 1.86) or infertility treatment (odds ratio, 1.06; 95% confidence interval, 0.60 to 1.87) was found in the Swedish data and no statistically significant increase in the use of ovulation stimulation in the French data. A strong association was found between the maternal use of anticonvulsants and infant craniostenosis, and a tentative association was found with the use of nitrofurantoin and two other nitrosatable drugs. There was no association with maternal subfertility or infertility treatment.

EFFICACY OF INTRAUTERINE INSEMINATION WITHOUT OVARIAN HYPERSTIMULATION FOR MALE OR CERVICAL FACTOR IN WOMEN AGED 40 OR OVER

The efficacy of intrauterine insemination (IUI) for male or cervical factor by age of female partner was determined in a retrospective analysis. Patients who underwent IUI therapy for cervical and/or male factor (n = 281) were classified by age at first IUI cycle: <40 years (n = 232), > or =40 years (n = 49). The indication for IUI was cervical factor if a postcoital test failed to show sperm with good forward progression at time of mature follicle; male factor was diagnosed if the semen analysis demonstrated either low count, low motility, antisperm antibodies, or subnormal hypoosmotic swelling test. Intrauterine insemination was performed in either natural cycles or following ovarian stimulation for the treatment of anovulation or follicular maturation defects. Cumulative probability of ongoing pregnancy (viable at end of first trimester) following 3 cycles of IUI was evaluated. Cumulative probability of ongoing pregnancy following 3 cycles of IUI was 28.2% for the younger group and 0.0% for the older group. The age groups did not differ in terms of infertility history, use of ovarian stimulation, or baseline semen parameters. Thus, the treatment of male and/or cervical factor by IUI is ineffective for women > or =40 years.

Malignant melanoma of the ovary and exposure to clomiphene citrate: A case report and review of the literature

Objective: The purpose of this article is to present a case of metastatic malignant melanoma of the ovary, a review of the current literature, and current recommendations for preventative and consultative management. Study Design: This is a case report and literature review. A 34-year-old woman had symptoms of pelvic abscess 1 month after clomiphene citrate stimulation for infertility. After a failed course of antibiotic therapy, an exploratory laparotomy was performed. Bilateral malignant melanomas of the ovary were discovered. The patient died 4 weeks later of disseminated metastases. Retrospectively, a history of a “mole” with unknown histopathologic characteristics had been removed from her arm 15 years earlier. A review of the literature was performed to provide current findings regarding malignant melanomas of the ovary, as well as to evaluate the potential relationship between the use of ovarian stimulating drugs and the development of melanomas. Results: Melanomas account for 3% of cancers, but the incidence of melanoma is rising. Genital melanomas are uncommon; the primary site is the vulva. Primary malignant melanoma of the ovary is rare; however, delayed recurrence from a primary skin site with metastasis to the ovary is documented. The literature suggests a possible relationship between the use of clomiphene citrate and an increase in melanomas of the skin. Conclusion: The gynecologist, as a primary provider, must be aware of the increasing incidence of malignant melanoma, as well as the recommendations for prevention. The gynecologist, as a consultant, must be aware of the risk of delayed recurrence of malignant melanoma. The potential for development of melanomas associated with the use of ovarian stimulation for infertility needs further monitoring and analysis. (Am J Obstet Gynecol 1999;180:1499-503.)

Laparoscopic approach to acute abdomen in first trimester pregnancy: three case reports

The acute abdomen in the first trimester of pregnancy presents a difficult diagnosis. As a result of the wider use of ovarian stimulation and advanced reproductive technologies, traditionally rare causes of acute abdomen now occur more frequently. We report two cases of heterotopic pregnancy at 9 and 12 weeks of gestation and one case of twisted adnexa in pregnancy as causes of acute abdomen. Proper diagnosis was only possible after diagnostic laparoscoopy. Treatment by salpingectomy and detorsion was performed by a laparoscopic procedure. The pitfalls and advantages of this approach are discussed.