WHO laboratory manual for the examination and processing of human semen

Endometriosis

The definition presented here represents the first realistic attempt by the scientific community to standardize the definition of poor ovarian response (POR) in a simple and reproducible manner. POR to ovarian stimulation usually indicates a reduction in follicular response, resulting in a reduced number of retrieved oocytes. It has been recognized that, in order to define the poor response in IVF, at least two of the following three features must be present: (i) advanced maternal age or any other risk factor for POR; (ii) a previous POR; and (iii) an abnormal ovarian reserve test (ORT). Two episodes of POR after maximal stimulation are sufficient to define a patient as poor responder in the absence of advanced maternal age or abnormal ORT. By definition, the term POR refers to the ovarian response, and therefore, one stimulated cycle is considered essential for the diagnosis of POR. However, patients of advanced age with an abnormal ORT may be classified as poor responders since both advanced age and an abnormal ORT may indicate reduced ovarian reserve and act as a surrogate of ovarian stimulation cycle outcome. In this case, the patients should be more properly defined as 'expected poor responder'. If this definition of POR is uniformly adapted as the 'minimal' criteria needed to select patients for future clinical trials, more homogeneous populations will be tested for any new protocols. Finally, by reducing bias caused by spurious POR definitions, it will be possible to compare results and to draw reliable conclusions.

/pdf/eshre-consensus-on-the-definition-of-poor-response-to-1caz0hdbpu.pdf

ESHRE consensus on the definition of ‘poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria

Clinical Trials: A Practical Approach

Endometriosis is defined as the presence of endometrial-type mucosa outside the uterine cavity. Of the proposed pathogenic theories (retrograde menstruation, coelomic metaplasia and Mullerian remnants), none explain all the different types of endometriosis. According to the most convincing model, the retrograde menstruation hypothesis, endometrial fragments reaching the pelvis via transtubal retrograde flow, implant onto the peritoneum and abdominal organs, proliferate and cause chronic inflammation with formation of adhesions. The number and amount of menstrual flows together with genetic and environmental factors determines the degree of phenotypic expression of the disease. Endometriosis is estrogen-dependent, manifests during reproductive years and is associated with pain and infertility. Dysmenorrhoea, deep dyspareunia, dyschezia and dysuria are the most frequently reported symptoms. Standard diagnosis is carried out by direct visualization and histologic examination of lesions. Pain can be treated by excising peritoneal implants, deep nodules and ovarian cysts, or inducing lesion suppression by abolishing ovulation and menstruation through hormonal manipulation with progestins, oral contraceptives and gonadotropin-releasing hormone agonists. Medical therapy is symptomatic, not cytoreductive; surgery is associated with high recurrence rates. Although lesion eradication is considered a fertility-enhancing procedure, the benefit on reproductive performance is moderate. Assisted reproductive technologies constitute a valid alternative. Endometriosis is associated with a 50% increase in the risk of epithelial ovarian cancer, but preventive interventions are feasible.

/pdf/endometriosis-pathogenesis-and-treatment-2d0xxwf9po.pdf

Endometriosis: pathogenesis and treatment

Oocyte vitrification as an efficient option for elective fertility preservation

The classic, unproven dogma that ovarian endometrioma should be removed in all infertile women prior to IVF has been recently questioned. There is currently insufficient data to clarify whether the endometrioma-related damage to ovarian responsiveness precedes or follows surgery. Both endometrioma-related injury and surgery-mediated damage may be claimed to be involved and the relative importance of these two insults remains to be clarified. Convincing evidence has emerged showing that responsiveness to gonadotrophins after ovarian cystectomy is reduced. Conversely, the impact of surgery on pregnancy rates is unclear since no deleterious effect has been reported. Of relevance here is that surgery exposes women to risk related to a demanding procedure whereas risks associated with expectant management are mostly anecdotal or of doubtful clinical relevance. We recommend proceeding directly to IVF to reduce time to pregnancy, to avoid potential surgical complications and to limit patient costs. Surgery should be envisaged only in presence of large cysts (balancing the threshold to operate with the cyst location within the ovary), or to treat concomitant pain symptoms which are refractory to medical treatments, or when malignancy cannot reliably be ruled out.

https://www.researchgate.net/profile/Juan_Garcia-Velasco/publication/23571718_Management_of_endometriomas_in_women_requiring_IVF_To_touch_or_not_to_touch/links/00b49529778e02fe20000000.pdf

Management of endometriomas in women requiring IVF: to touch or not to touch

https://www.fertstert.org/article/S0015-0282(05)00598-4/pdf

The aromatase inhibitor letrozole increases the concentration of intraovarian androgens and improves in vitro fertilization outcome in low responder patients: a pilot study.

Five years' experience using oocyte vitrification to preserve fertility for medical and nonmedical indications

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) typically occurs when ovaries are primed with FSH/ LH and subsequently exposed to hCG. The ultimate pathophysiological step underlying this clinical picture is increased vascular permeability (VP). METHODS: A search of the literature was carried out using PubMed and the authors’ files. RESULTS: In rodents and humans, the expression of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR-2) mRNA increases during ovarian stimulation. With the administration of hCG, the expression of each rises to a maximum. Expression of VEGF/VEGFR-2 mRNAs correlates with enhanced VP, with both peaking 48 h following an injection of hCG. Immunohistochemistry shows the presence of VEGF and VEGFR-2 proteins in the granulosa-lutein and endothelial cells of the entire corpus luteum. Increased VP may be mediated through adhesion molecules such as VE-cadherin, which is involved in the loosening of endothelial intercellular junctions. These findings regarding the pathophysiology of OHSS suggest that the syndrome can be prevented by inducing ovulation with LH or GnRH analogues, which prevent VEGF overexpression. Also, co-administration of a dopamine agonist inhibits phosphorylation of the receptor VEGFR-2. In a trial of 69 oocyte donors, the incidence of moderate OHSS was 20% with the dopamine agonist cabergoline and 44% with a placebo (P 5 0.04). CONCLUSIONS: The pathophysiological mechanisms involved in OHSS suggest potential preventive approaches, but larger trials are necessary for evaluating the efficacy and safety of the pharmaco-prevention of OHSS.

/pdf/targeting-the-vascular-endothelial-growth-factor-system-to-drqc7sa0a2.pdf

Juan A. Garcia-Velasco

Papers

Oocyte vitrification as an efficient option for elective fertility preservation

Management of endometriomas in women requiring IVF: to touch or not to touch

The aromatase inhibitor letrozole increases the concentration of intraovarian androgens and improves in vitro fertilization outcome in low responder patients: a pilot study.

Five years' experience using oocyte vitrification to preserve fertility for medical and nonmedical indications

Targeting the vascular endothelial growth factor system to prevent ovarian hyperstimulation syndrome