'An ounce of prevention is worth a pound of cure': the case for and against GnRH-agonist for fertility preservation.

The late effects of cancer treatment have recently gained a worldwide interest among reproductive endocrinologists, oncologists, and all health-care providers, and the protection against iatrogenic infertility caused by chemotherapy assumes a high priority. Here, we summarize the case for and against using GnRH-agonist for fertility preservation and minimizing chemotherapy-induced gonadotoxicity. The rationale and philosophy supporting its use is that preventing premature ovarian failure (POF) is preferable to treating it, following the dictum: 'an ounce of prevention is worth a pound of cure'. Despite many publications on this subject, there are many equivocal issues necessitating summary. Until now, 20 studies (15 retrospective and 5 randomized, controlled trials) have reported on 1837 patients treated with GnRH-a in parallel to chemotherapy, showing a significant decrease in POF rate in survivors versus 9 studies reporting on 593 patients, with results not supporting GnRH-a use. Patients treated with GnRH-a in parallel to chemotherapy preserved their cyclic ovarian function in 91% of cases when compared with 41% of controls, with a pregnancy rate of 19-71% in the treated patients. Furthermore, seven meta-analyses have concluded that GnRH-a are beneficial and may decrease the risk of POF in survivors. However, controversy still remains regarding the efficiency of GnRH-a in preserving fertility. Since not all the methods involving fertility preservation are unequivocally successful and safe, these young patients deserve to be informed of all the various modalities to minimize gonadal damage and preserve ovarian function and future fertility. Combining several methods for a specific patient may increase the odds for minimally invasive fertility preservation.

Effect of primary human endometrial stromal cells on epithelial cell receptivity and protein expression is dependent on menstrual cycle stage.

BACKGROUND: Successful implantation requires a receptive endometrium. We hypothesized that effects of endometrial stromal cells (ESC) on epithelial cell receptivity and trophoblast-endometrium interaction are menstrual cycle dependent. METHODS: An endometrial in vitro 3D co-culture model of primary human ESC with the endometrial epithelial cell line (RL95-2) was constructed. Co-cultures were prepared using primary ESC from biopsies taken before the window of implantation (ESCbw) and during the window of implantation (ESCw), on cycle days 10-17 and 19-23, respectively. RL95-2 served as a constant parameter upon which the influence of ESC from different phases of the cycle was investigated. proMMP-2 (MMP, matrix metalloproteinase) and proMMP-9 secretion was tested in response to progesterone. Progesterone receptor B (PR-B) and plexin B1 protein expression and mRNA levels were investigated using immunofluorescence and RT-PCR, respectively. RESULTS: Progesterone increased proMMP-2 secretion in primary ESCbw (P = 0.0046) but decreased proMMP-2 and proMMP-9 secretion in ESCw (P < 0.0005). In the presence of ESCbw, JAR spheroid attachment rate to overlying RL95-2 cells was decreased (P < 0.0001), whereas in the presence of ESCw, attachment rate was unchanged. Progesterone treatment restored epithelial cell receptivity in co-culture with ESCbw (P = 0.00004). A correlation between spheroid attachment rate and plexin B1 mRNA level was observed (P = 0.01). PR-B protein and mRNA level were influenced by the interplay between RL95-2 and stromal cells. CONCLUSION: The effects of human primary ESC on epithelial cell receptivity and trophoblast-endometrium interaction depended upon whether the ESC were taken before or during the window of implantation.