Roxana M. Popovici

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.

Paracrine effects of uterine leucocytes on gene expression of human uterine stromal fibroblasts

The endometrium contains a distinct population of immune cells that undergo cyclic changes during the menstrual cycle and implantation. The majority of these leucocytes are uterine NK (uNK) cells, however how these cells interact with uterine stromal fibroblasts remains unclear. We therefore investigated the paracrine effect of medium conditioned by uterine decidual leucocytes (which are enriched for uNK cells) on the gene expression profile of endometrial stromal fibroblasts in vitro using a cDNA microarray. Our results, verified by real-time PCR, ELISA and FACS analysis, reveal that soluble factors from uterine leucocytes substantially alter endometrial stromal fibroblast gene expression. The largest group of up-regulated genes found was chemokines and cytokines. These include IL-8, CCL8 and CXCL1, which have also been shown to be stimulated by contact of stromal fibroblasts with trophoblast, suggesting that uNK cells work synergistically to support trophoblast migration during implantation. The decidual leucocytes also up-regulated IL-15 and IL-15Ralpha in stromal fibroblasts which could produce a niche for uNK cells allowing proliferation within and recruitment into the uterus, as seen in bone marrow. Overall this study demonstrates, for the first time, the paracrine communication between uterine leucocytes and uterine stromal fibroblasts, and adds to the understanding of how the uterine immune system contributes to the changes seen within the cycling endometrium.

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.

Psychotherapy With Somatosensory Stimulation for Endometriosis-associated Pain: A Randomized Controlled Trial

OBJECTIVE: To evaluate whether psychotherapy with somatosensory stimulation is effective for the treatment of pain and quality of life in patients with endometriosis-related pain. METHODS: Patients with a history of endometriosis and chronic pelvic pain were randomized to either psychotherapy with somatosensory stimulation (ie, different techniques of acupuncture point stimulation) or wait-list control for 3 months, after which all patients were treated. The primary outcome was brain connectivity assessed by functional magnetic resonance imaging. Prespecified secondary outcomes included pain on 11-point numeric rating scales (maximal and average global pain, pelvic pain, dyschezia, and dyspareunia) and physical and mental quality of life. A sample size of 30 per group was planned to compare outcomes in the treatment group and the wait-list control group. RESULTS: From March 2010 through March 2012, 67 women (mean age 35.6 years) were randomly allocated to intervention (n=35) or wait-list control (n=32). In comparison with wait-list controls, treated patients showed improvements after 3 months in maximal global pain (mean group difference −2.1, 95% confidence interval [CI] −3.4 to −0.8; P=.002), average global pain (−2.5, 95% CI −3.5 to −1.4; P<.001), pelvic pain (−1.4, 95% CI −2.7 to −0.1; P=.036), dyschezia (−3.5, 95% CI −5.8 to −1.3; P=.003), physical quality of life (3.8, 95% CI 0.5–7.1, P=.026), and mental quality of life (5.9, 95% CI 0.6–11.3; P=.031); dyspareunia improved nonsignificantly (−1.8, 95% CI −4.4 to 0.7; P=.150). Improvements in the intervention group remained stable at 6 and 24 months, and control patients showed comparable symptom relief after delayed intervention. CONCLUSION: Psychotherapy with somatosensory stimulation reduced global pain, pelvic pain, and dyschezia and improved quality of life in patients with endometriosis. After 6 and 24 months, when all patients were treated, both groups showed stable improvements. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT01321840.

Psychotherapy With Somatosensory Stimulation for Endometriosis-Associated Pain: The Role of the Anterior Hippocampus

BACKGROUND Endometriosis is a gynecological disorder affecting 6%-10% of all women in their reproductive age. There is an emerging view in the literature that psychological trauma plays a central role in the pathogenesis of pelvic pain, one of the core symptoms of endometriosis. Here we report central nervous system mechanisms of a novel combination of psychotherapy and somatosensory stimulation that has recently shown remarkable effects in reducing pain, anxiety, and depressive symptoms in these patients. METHODS We conducted a randomized controlled trial; 67 patients with severe endometriosis-associated pain (maximum pain: 7.6 ± 2.0, average pain: 4.5 ± 2.0 on a 10-point numeric rating scale) were included in the study and randomly allocated to intervention (35 patients) or waitlist control (32 patients) groups. Resting-state functional magnetic resonance imaging was used to assess brain connectivity of these patients at baseline, after 3 months of therapy, and after 6 months. The analysis focused on the hippocampus. RESULTS We identified a cortical network comprising the right anterolateral hippocampus-a region modulating the hypothalamic-pituitary-adrenal axis-and somatosensory, viscerosensory, and interoceptive brain regions. Regression analysis showed that reduction in connectivity predicted therapy-induced improvement in patients׳ anxiety. CONCLUSIONS We have identified a putative neurobiological mechanism underlying the potent combination of psychotherapy and somatic stimulation in treating symptoms of endometriosis.

Psychotherapy With Somatosensory Stimulation for Endometriosis-Associated Pain: A Randomized Controlled Trial

The underlying causal mechanisms for endometriosis are poorly understood. There is a weak correlation between the severity of organic pathology and reported pain intensity in women with endometriosis. Both systemic hormonal therapy and surgery improve symptoms of pelvic pain, but recurrence rates are high after the medication is discontinued or following surgery. A retrospective case study (Meissner 2010;Forsch Komplementarmed 17: 314) reported that a combination of psychotherapy and somatosensory stimulation (different techniques to stimulate acupuncture points) could be effective in improving pain and infertility associated with endometriosis, preferably when combined with other elements ofmultimodal pain therapy. This randomized controlled trial was designed to evaluate whether psychotherapy with somatosensory stimulation is effective for the treatment of pain and quality of life in patients with endometriosis-related pelvic pain. Eligible patients were adult females aged 18 to 40 years with a history of endometriosis and moderate to severe chronic pelvic pain. The predefined primary outcome was brain functional connectivity assessed by magnetic resonance imaging (MRI). The predefined secondary outcomes-maximal and average global pain, maximal pelvic pain, dyschezia, and dyspareunia-were assessed by validated 11-point numerical rating scales. Physical and mental quality of life was also assessed. Between March 2010 andMarch 2012, 67 patients (mean age, 35.6 years) were randomly assigned to intervention (n = 35) or wait-list control (n = 32). Follow-up data were available for 60 patients (90%) at 3 months, 41 patients (61%) at 6 months, and for 56 patients (84%) at 24 months. Compared with wait-list controls, patients in the intervention group showed improvements after 3 months in maximal global pain (mean group difference, -2.1;95% confidence interval [CI], -3.4 to -0.8;P = 0.002), average global pain (-2.5;95% CI, -3.5 to -1.4;P < 0.001), pelvic pain (-1.4;95% CI, -2.7 to -0.1;P = 0.036), dyschezia (-3.5;95% CI, -5.8 to -1.3;P = 0.003), physical quality of life (3.8;95% CI, 0.5-7.1, P = 0.026), and mental quality of life (5.9;95% CI, 0.6-11.3;P = 0.031). Improvements in dyspareunia did not differ significantly from wait-list controls (-1.8;95% CI, -4.4 to 0.7;P = 0.15). At 6 and 24 months, improvements in the intervention group remained stable, and after delayed intervention at 3 months, comparable symptom relief was achieved in the former control group at 6 and 12 months. These data show that psychotherapy with somatosensory stimulation reduces global pain, pelvic pain, and dyschezia and improved quality of life in a population of patients with endometriosis. Both groups showed stable improvements after 6 and 24 months, when all patients were treated.