Barbara Lawrenz

Ovarian stimulation to cryopreserve fertilized oocytes in cancer patients can be started in the luteal phase.

OBJECTIVE To analyze if oocytes can be obtained in all patients before cancer treatment within 2 weeks by initiating ovarian stimulation during the follicular or luteal phase. DESIGN Prospective controlled multicenter trial. SETTING Four university-based centers. PATIENT(S) Forty cancer patients before chemotherapy. INTERVENTION(S) Twenty-eight patients were stimulated with gonadotropins in the follicular phase (group I). In 12 patients (group II), ovarian stimulation was initiated in the luteal phase, and these received GnRH antagonists and recombinant FSH. In 14 patients, 143 oocytes were further processed for fertilization by intracytoplasmic sperm injection (ICSI). MAIN OUTCOME MEASURE(S) Number of oocytes aspirated after ovarian stimulation, cumulative FSH/hMG dosage, viability and maturity of oocytes, and fertilization rate by ICSI. RESULT(S) Patients in group I (age 27.6 +/- 4.9 yrs) were stimulated on average for 10.6 days, and patients in group II (age 31.2 +/- 5.7 yrs) for 11.4 days. Total amount of FSH was on average 2,255 IU (I) and 2,720 IU (II) per patient. Average and median numbers of aspirated oocytes were, respectively, 13.1 and 11.5 (I) versus 10.0 and 8.5 (II); 83.7% (I) and 80.4% (II) of the oocytes were mature and viable and could be treated by ICSI. Fertilization rate was 61.0% (I) versus 75.6% (II). CONCLUSION(S) This pilot study suggests that oocytes can be obtained before cancer treatment efficiently irrespective of the phase of the menstrual cycle.

ERK-mediated regulation of leukotriene biosynthesis by androgens: A molecular basis for gender differences in inflammation and asthma

5-Lipoxygenase initiates the biosynthesis of leukotrienes, lipid mediators involved in normal host defense and in inflammatory and allergic disorders. Despite an obvious gender bias in leukotriene-related diseases (e.g., asthma), gender aspects have been neglected in studies on leukotrienes and 5-lipoxygenase. Here, we show that leukotriene formation in stimulated whole blood or neutrophils from males is substantially lower compared with females, accompanied by changed 5-lipoxygenase trafficking. This is due to gender-specific differential activation of extracellular signal-regulated kinases (ERKs). The differences are directly related to variant male/female testosterone plus 5α-dihydrotestosterone levels, and addition of 5α-dihydrotestosterone to female blood or neutrophils reduced the high (female) LT biosynthesis capacity to low (male) levels. In conclusion, regulation of ERKs and leukotriene formation by androgens constitutes a molecular basis for gender differences in the inflammatory response, and in inflammatory diseases such as asthma.

Improving fertility preservation in cancer: ovarian tissue cryobanking followed by ovarian stimulation can be efficiently combined

This pilot study evaluated whether combination of partial removal of ovarian tissue for cryobanking followed by ovarian stimulation and cryopreservation of oocytes can improve the efficacy of fertility preservation without further delaying cancer treatment. Initial partial removal of ovarian tissue did not substantially affect the average number and quality of retrieved oocytes after ovarian stimulation in this study.

Efficacy and safety of ovarian stimulation before chemotherapy in 205 cases

Ovarian stimulation and cryopreservation of fertilized oocytes before cancer therapy is the best established and efficient fertility preservation technique and should still be considered before chemotherapy. Within a short time frame of 2 weeks, between 8.6 (18-25 y) and 5.1 (36-40 y) fertilized oocytes can be cryopreserved.

Fertility preservation methods in young women with systemic lupus erythematosus prior to cytotoxic therapy: experiences from the FertiProtekt network

Objectives: Despite new treatment options, some patients with systemic lupus erythematosus (SLE) need to be treated with the cytotoxic agent cyclophosphamide (CYC). Unlike malignant disease, there are no recommendations for ovarian protection in SLE. The clinical experience of the FertiPROTEKT network as well as recommendations after literature review will be presented in this paper. Methods: Retrospective analyses of counselling and treatment data from the FertiPROTEKT register with special respect to SLE patients under 40 years prior to planned CYC treatment. Results: A total of 2836 patients were advised prior to cytotoxic treatment in one of the FertiPROTEKT centres during January 2007 to November 2011. Of those, 68 patients (mean age 25 +/− 6.07years) were counselled for severe SLE. Only five women did not make use of a fertility preservation method. Sixty-three patients (92.6%) decided in favour of a fertility preservation method. The largest proportion (91.2%) opted for treatment with a GnRH analogue. Ovarian tissue removal for cryoconservation was performed in 16 patients (25%). Stimulation therapy for cryoconservation of fertilized egg cells was performed in three patients (4.4%). Conclusions: When counselling patients with SLE for fertility preservation one has to be aware of the disease-specific risks. According to the literature, a safe and effective option in SLE up to now has been the use of a GnRH analogue. Cryoconservation of ovarian tissue must still be seen as an experimental treatment, but as data on removal, cryoconservation, retransplantation and pregnancies are steadily rising, this presents a promising option for young SLE patients. Cryoconservation of oocytes must be very critically evaluated due to the need for a stimulation therapy and should only be performed after particular consideration of the individual risks.

Ovarian reserve alterations in premenopausal women with chronic inflammatory rheumatic diseases: impact of rheumatoid arthritis, Behçet’s disease and spondyloarthritis on anti-Müllerian hormone levels

OBJECTIVE Recent publications have shown a negative influence of SLE on female ovarian reserve. Other authors have not found a significant impact of Crohns disease or early RA on anti-Müllerian hormone (AMH) levels. This study aimed to investigate the potential effect of Behçets disease (BD), RA and SpA on ovarian reserve as reflected by serum AMH levels. METHODS Serum samples from 33 RA, 32 SpA and 30 BD patients without previous cytotoxic treatment were analysed and compared with age-matched, healthy controls. AMH was quantified using a standard ELISA with a standard value of 1-8 ng/ml; values <1 ng/ml defined a reduced ovarian reserve. RESULTS Median age was 26, 28.5 and 33 years and median disease duration was 6, 5.9 and 7 years for RA, SpA and BD patients, respectively. Compared with healthy controls, patients had significantly reduced AMH levels, with a median value for RA of 1.8 ng/ml (control 2.4 ng/ml; P = 0.009), for SpA of 1.5 ng/ml (control 2.3 ng/ml; P = 0.013) and for BD of 1.1 ng/ml (control 1.9 ng/ml; P = 0.007). HLA-B27 had a negative influence on ovarian reserve in SpA patients, whereas other serological parameters did not in the other diseases. CONCLUSION This is the first study to show a reduced ovarian reserve in patients with RA, SpA or BD. Together with our findings in SLE, we conclude a negative influence of chronic rheumatic diseases on ovarian reserve.

Pregnancy after Successful Cancer Treatment: What Needs to Be Considered?

Over the last decade, advances in oncology led to improved treatment results and increasing numbers of long-term cancer survivors. Fulfilling the desire to have children is important for many patients after cancer treatment. Consequently, oncologists, gynecologists and obstetricians are seeing more patients who wish to conceive after treatment. The necessary prerequisites that should be considered when supporting a planned pregnancy after cancer treatment are discussed in this article. The possible consequences of chemotherapy and radiotherapy on the course of pregnancy and the health of the offspring, as well as the interactions between cancer and pregnancy, are reviewed with the focus on childhood cancer, malignant lymphomas, and breast cancer. Despite chemo- or radiotherapy, neither the teratogenic risk nor the risk of adventitious cancers appears to be increased for the offspring of cancer survivors. However, there is a slightly higher risk of miscarriage after chemotherapy. In case of radiation to the uterus, there is a higher risk of premature birth, intrauterine growth retardation, and increased perinatal mortality. The effect is more pronounced after prepubertal radiation than for postpubertal radiation. The former cancer patient’s desire to conceive can nevertheless be supported, given that pregnancy and birth are closely monitored.

Lower Extremity Compartment Syndrome after Laparoscopic Radical Hysterectomy: Brief Report of an Unusual Complication of Laparoscopic Positioning Requirements

Compartment syndrome of the lower extremities is a clinically and medicolegally potentially devastating complication. Recently, the more widespread use of advanced laparoscopic surgical techniques, dealing with complex gynecologic diseases, including gynecologic malignancies and severe endometriosis, has led to an increasing number of laparoscopic surgeries of long duration (> 4 hours). With only very few case reports published in the gynecologic literature, increased attention is warranted with regard to this clinically insidious complication. We present a case report and review of the existing literature and discuss the main clinical features as well as preventive and therapeutic options.

Fertility preservation in young female lymphoma patients: review of available options and initial experiences with their implementation in clinical routine.

Background: High cure rates in women suffering from Hodgkin’s disease or aggressive non-Hodgkin’s lymphoma are often achieved at the cost of impaired ovarian function or infertility. Different strategies can be offered to protect fertility. Early experiences with the implementation of a specialised fertility preservation clinic are analysed with the aim to assess the need for and acceptance of the clinic, as well as the delay of treatment caused by the different approaches. Available options are reviewed. Patients and Methods: Data on underlying malignancy and fertility preservation measures in women of childbearing age treated for aggressive lymphoma and Hodgkin’s disease with curative intent between November 2006 and January 2010 were retrospectively analysed. Results: Among 111 female lymphoma patients, 30 were eligible for counselling. Nineteen accepted the offer. The main reason for declining was completed family planning. Eight further patients were referred from elsewhere. Of the counselled patients, 96% decided to pursue at least 1 protective strategy, 39% chose an invasive procedure (cryopreservation of ovarian tissue or oocyte aspiration following hormonal stimulation). These procedures deferred the start of systemic treatment within the expected range, no undue delays were observed. Conclusions: Female lymphoma patients have a large demand for counselling about measures to protect fertility. In a proper setting, counselling and intervention can be offered without undue delays menacing the chance for cure.

Characteristics and attitudes of women in relation to chosen fertility preservation techniques: a prospective, multicenter questionnaire-based study with 144 participants

OBJECTIVE What are the patients attitudes about their fertility and about the counselling process at the time when fertility preservation counselling is performed? STUDY DESIGN A survey regarding fertility concerns and counselling performance in relation to the chosen fertility preservation procedure such as no treatment, GnRH agonists, and freezing of ovarian tissue or oocytes/zygotes was prospectively conducted in four university centres and one private centre, all belonging to the network FertiPROTEKT in Germany and Switzerland. RESULTS All women (n=145) received a questionnaire at the first counselling appointment. The mean age of the patients was 30 years (±5.8, range 17-43 years). 91% were referred by their treating oncologists. Single patients preferred invasive strategies, such as freezing of oocytes/zygotes (44.3%) or freezing of ovarian tissue (36%), whereas only 19.7% opted for no treatment/GnRH agonists. In married couples, the proportions were 28.9%, 31.1% and 40.0% respectively. Women without children also opted more frequently for invasive strategies, such as freezing of oocytes/zygotes (84.5%) or freezing of ovarian tissue (74.1%), and less frequently for no treatment/GnRH agonists (63.3%). Physical and psychological status, current and future fertility concerns and satisfaction with the counselling process were equal in all treatment groups. CONCLUSION As fertility concerns and attitudes about the counselling process were independent from the fertility preservation procedure chosen, the preferred treatment can hardly be predicted and therefore all women should be counselled about all possible fertility preservation techniques.