Aggressive chemotherapy has improved the life expectancy for reproductive-age women with breast cancer, but it often causes infertility or premature ovarian failure due to destruction of the ovarian reserve. Many questions concerning fertility preservation in breast cancer patients remain unanswered -for example, whether fertility preservation methods interfere with chemotherapy, and whether subsequent pregnancy has negative effects on the prognosis. Fertility preservation is a critical factor in decisionmaking for younger breast cancer patients, however, and clinicians should address this. The present article reviews the incidence of chemotherapy-induced amenorrhea, and discusses fertilitypreservation options and the prognosis for patients who become pregnant after breast cancer. IntroductionBreast cancer is the most common malignancy in women of reproductive age, and about 13% of all breast cancer diagnoses are made in women younger than age 45 years [1]. In Germany, the average age of primiparas is 29.8 years [2], which means that many breast cancer patients have not completed their family planning and wish to have children after the diagnosis of breast cancer. The majority of women diagnosed with early-stage breast cancer today have an excellent long-term prognosis, but many of them will undergo a temporary or permanent cessation of menses. Although premature ovarian insufficiency can improve the breast cancer prognosis for women with hormone-positive breast cancer, these women have to face subsequent infertility and many psychological problems [3].In the present review, we discuss the effect of the most up-todate chemotherapy regimens for breast cancer on fertility, and we analyze the options for fertility preservation, as well as the various in vitro fertilization (IVF) protocols that can be applied in this specific patient group. Finally, a review of the available studies on the effect of a subsequent pregnancy on the outcome in breast cancer survivors is conducted. Effect of chemotherapy for breast cancer on fertilityThis section discusses the effect on fertility of chemotherapy for breast cancer (Table 1) [4][5][6][7][8][9][10][11][12][13]. The risk of chemotherapyrelated amenorrhea depends on the patient's age, on the specific chemotherapeutic agents used, and on the total dose administered. Older women have a higher incidence of complete ovarian failure and permanent infertility in comparison with younger women [14]. This higher incidence can be explained by younger women's larger primordial follicle reserve, which declines with age.With regard to the chemotherapy regimen, according to Meirow, alkylating agents (for example, cyclophosphamide) involve the greatest risk for inducing ovarian failure among all chemotherapeutic agents (odds ratio 3.98 in comparison with unexposed patients) [15]. The higher the cumulative dose of cyclophosphamide, the higher the observed incidence of menopause. Goldhirsch and colleagues reported that, with the classic cyclophosphamide, methotrexate, and 5-fluoroura...
Cetrorelix pretreated with OCs resulted in similar number of oocytes retrieved compared with a long buserelin protocol. Both regimens were well tolerated and allowed scheduling of the oocyte retrieval, with only small number of retrievals falling on a weekend or public holiday.
Seventy-eight follicles and their follicular fluid were aspirated from 46 women undergoing in vitro fertilization (IVF) procedures after stimulation of the ovaries with a low-dose human menopausal gonadotropin/human chorionic gonadotropin stimulation regimen. The concentrations of estradiol (E2), progesterone (P), testosterone (T), and prolactin (PRL) were measured in follicular fluid and related to the maturation of the oocyte-corona-cumulus complex (OCCC) and the fertilization of oocytes. Follicles containing mature oocytes had significantly higher follicular fluid E2 and P levels than follicles with intermediate and immature oocytes. A constant decrease in PRL and T values with advancing follicular maturation was observed. Similar results were obtained when the fertilizing ability of the oocytes was examined. The gradual decline in follicular fluid PRL and T levels during follicular development was connected with increasing E2 and P biosynthesis and therefore seems to be an important precondition for normal follicular and oocyte maturation.
The aim of this study was to examine the effect of an additional administration of recombinant luteinizing hormone (r-LH) to a gonadotropin-releasing hormone agonist (GnRHa) long protocol using recombinant follicle-stimulating hormone (r-FSH). In particular we determined whether such a stimulation protocol would be more effective in women (1) who respond poorly to stimulation with GnRHa long protocol using r-FSH only, and (2) whose LH concentrations after down-regulation in the cancelled cycle were low but above the values reported in the literature to be sufficient for folliculogenesis. After GnRHa desensitization 150 IU r-FSH and 75 IU r-LH were administered subcutaneously daily to six normogonadotropic women with low response to ovarian hyperstimulation using a GnRHa long protocol with r-FSH and low LH concentrations after down-regulation in the cancelled cycle. All six women had an oocyte retrieval and an embryo transfer after follicular stimulation. One women conceived but had a miscarriage in the eleventh week of gestation. Our results suggest that women with low response to a GnRHa long protocol with r-FSH, and whose LH concentration after down-regulation in the cancelled cycles were low, benefit from the additional administration of r-LH in a GnRHa long protocol using r-FSH. It seems that due to the additional administration of r-LH the LH concentration in the follicular phase is sufficient to support folliculogenesis.
Objective: The aim of the study was to compare the perinatal outcome of spontaneously conceived twins with those conceived after in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Material and Methods: A retrospective study was performed. Clinical data of 188 twin pregnancies was collected from the Department of Obstetrics and Gynecology, University Hospital of Mainz for the years 1996-2006. The twins were divided into 2 groups according to the manner of conception: spontaneously conceived twins (n = 142) and twins (n = 46) conceived after IVF and ICSI. In order to investigate the perinatal outcome of spontaneous twins and twins conceived by assisted reproductive technology (ART), we evaluated the following parameters: maternal age, fertility, nulliparity rate, gestational age, mode of delivery, fetal weight and Apgar score. Results: No significant difference was found in maternal age, fertility and gestational age between spontaneous twins and IVF/ICSI twins. Maternal gestational age was 255 days in the spontaneous group and 254 days in IVF/ICSI group. Fetal weight and Apgar score were similar between the two groups. The nulliparity rate was higher in IVF/ICSI group. Obviously there were more cesarean sections in the IVF/ICSI group than in the spontaneous group (76.2 % and 42.5 %, respectively). Conclusions: Duration of gestation, neonatal birth weight and Apgar score were similar between IVF/ICSI twins and spontaneous twins. IVF/ICSI twins had a higher cesarean section rate.
During cycle stimulation for in-vitro fertilisation (IVF) some patients develop hyperprolactinaemia. Since prolactin (PRL), being an aromatase inhibitor, can interfere with follicular fluid steroid metabolism, we examined the influence of high serum PRL levels on the endocrine response and fertilisation rate of oocytes. 33 consecutive patients stimulated by hMG/hCG for IVF were included in this study. Two groups of patients were established: Group 1 consisting of 18 patients with serum PRL levels less than or equal to 25 ng/ml, and group 2 containing 15 patients, who developed PRL levels greater than 25 ng/ml during cycle stimulation. The serum oestradiol (E2), progesterone (P) and PRL levels 3, 2 and 1 day before and at the day of follicle puncture were evaluated. The decrease of E2 levels at the day of oocyte retrieval was significantly steeper in group 1. The P levels 2 days before oocyte retrieval were significantly higher in group 1 indicating the onset of preovulatory luteinization. Luteinization after the hCG injection was more effective in group 1 resulting in significantly higher P levels. Fertilisation and cleavage rates were significantly higher in patients with normal PRL levels. High serum PRL levels therefore might indicate an interference in follicular and oocyte development leading to oocytes of inferior quality.
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