Future Prospects

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Future Prospects



Renato Pasquali




Introduction


In the last two decades, major improvements in ovulation induction protocols and techniques, including assisted reproductive technologies (ARTs) have been achieved, leading to a steady rise in pregnancy rates as demonstrated by national statistics worldwide. Anovulatory infertility, particularly the type due to polycystic ovary syndrome (PCOS), represents one of the major factors responsible for the increasing resort to ovulation induction techniques worldwide (1). Because the increasing age of individuals with infertility problems represents a major concern, practitioners, gynecologists, and other specialists are faced with a rise in direct or indirect questions and problems about ovulation induction techniques.




Evaluation of Ovarian Reserve


The development of knowledge on the role of the anti-Müllerian hormone (AMH) in ovarian physiology and pathology has opened a new chance in the diagnostic workup of female infertility. The measurement of blood concentrations of AMH has been applied to a wide array of clinical conditions based on its ability to reflect the number of antral and pre-antral follicles in the ovaries. In addition, AMH blood levels may help in choosing the ovarian stimulation protocol and the dose of gonadotropins to begin with in order to limit the risks of ovarian hyperstimulation syndrome (OHSS) or cancellation of cycles due to poor ovarian response although this still represents a matter of further research. Despite all these premises, it should be noted that the evaluation of AMH has not yet been accepted as an alternative to ultrasonography in the diagnosis of PCOS nor in that of premature ovarian failure although it has been proved to be useful in daily practice. This is partly due to the fact that we ought to have a reliable assay to measure AMH whereas, at present, there is evidence that most assays are lacking in accuracy, precision, sensitivity, and reproducibility. AMH assays continue to evolve and technical issues remain. The absence of an international standard is a key issue, particularly in the area of infertility treatment (2).




Treatment with Gonadotropins


Ovarian stimulation with gonadotropins is considered a second-line treatment for the PCOS patients with infertility (3). At present, the use of gonadotropins and gonadotropin-releasing hormone (GnRH) analogues has allowed the tailoring, based on an individual basis, of several ovarian stimulation procedures. The two most commonly used gonadotropin forms are urinary human menopausal gonadotropin (hMG) and recombinant follicle stimulating hormone (FSH) in combination with gonadotropin-releasing hormone (GnRH) agonists or antagonists. Several studies have shown that gonadotropins may be effective after an ovarian stimulation with clomiphene citrate (CC) in patients with CC resistance; however, approximately two thirds of patients may positively respond in term of live birth rates (4). Recently, low-dose FSH treatment has been found to be superior to CC as first-line therapy for ovulation induction (4). The Thessaloniki consensus provided normative protocols while planning ovulation induction in PCOS women and emphasized the negative role of obesity on expected outcomes (3). Again, there are also studies showing that metformin administration may increase the live birth and pregnancy rate in PCOS patients who receive gonadotropins for ovulation induction (5).


In general, none of the available studies include patients who are potentially responsive, and they exclude those potentially not responsive, such as those with obesity or other dysmetabolic conditions. I suggest that much more attention should be paid to defining responsiveness before any treatment is planned on an individual or categorical basis. Defining unresponsiveness ex-post can be useful on a scientific basis, but it does not fit with the individual needs of each individual patient. In a clinical background, each patient expects the most effective treatment based on his or her condition and his or her needs. In the following section focusing on “Obesity, Infertility, PCOS, and Weight Loss: Do We Need a More Personalized Approach?”, I discuss some potential aspects that should be considered to finalize each treatment according to these concepts. For example, sustained weight loss could be very important before gonadotropin treatment for ovulation induction. Many more clinical studies are warranted in this area.




Diet Influences and Potential Effects on Infertility


A healthy diet may improve fertility for women with ovulatory dysfunction although data regarding the effects of variations in diet on fertility in anovulatory women, particularly those with PCOS, are few. Apart from lowering the malformation risk by periconceptional supplementation of folic acid, data on dietary integration with different micronutrients are often anecdotal. A potential efficacy of the Mediterranean dietary patterns has been emphasized in some studies. Other studies suggested that avoiding trans fats could also be of some help (6). Due to the potential benefit and low costs of a preconception diet, which still lacks powerful scientific evidence, much more research in this area and larger trials should be carried out, particularly before an ovulation induction protocol is planned.


Vitamin D levels are often lower than normal in obese PCOS women. The role of vitamin D in reproductive physiology has been investigated in the last year, and several studies have documented that supplementation with vitamin D may significantly improve ovulation in women with PCOS and be a possible benefit in patients undergoing ovulation induction techniques. Due to the potential benefit and low costs of a preconception diet, much more research in this area is warranted, particularly before an ovulation induction protocol is planned.


Specific interest has arisen on the potential role of advanced glycation end products (AGEs) in both the etiology of PCOS and related infertility. Once formed, AGEs may damage cellular structures via a number of mechanisms, after accumulation in various tissues, including the ovaries (7

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May 9, 2017 | Posted by in GYNECOLOGY | Comments Off on Future Prospects

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