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Abstract Background The injectable gonadotropin-releasing hormone (GnRH) antagonists have traditionally been used for ovulation suppression during controlled ovarian hyperstimulation for in vitro fertilization (IVF), leading to increased painful daily injections and cost. The use of the oral GnRH antagonist elagolix for ovulation suppression in IVF has not been studied. Methods This retrospective cohort study of patients undergoing IVF who received either oral elagolix 50 mg every other day or ganirelix/cetrotide injection daily for ovulation suppression during controlled ovarian hyperstimulation included 269 patients, 173 in the elagolix group and 96 in the ganirelix/cetrotide group. The main outcome was the suppression of luteinizing hormone (LH) blood levels, reflecting ovulation suppression. Results Age, body mass index, anti-Müllerian hormone, baseline follicle-stimulating hormone, antral follicles count, dose of medications used, number of days of ovarian stimulation, and peak estradiol (E2) levels were similar in both groups. When blood LH and E2 levels were measured before intake and the day after intake of either elagolix or ganirelix/cetrotide, both groups had significant and similar drop in LH levels and increase in E2 levels. When comparing IVF cycle outcomes in both groups, the number of oocytes retrieved, number of mature oocytes, fertilization rate, blastocyst formation rate, euploidy rate, and endometrial lining thickness at the time of the trigger were all similar. Conclusion Oral GnRH antagonist, a much cheaper and less invasive medication that is used at a lower frequency, showed comparable ovulation suppression to the costly injectable GnRH antagonist. Further studies are required to evaluate the effect of oral GnRH antagonist on endometrial lining receptivity and pregnancy outcomes, especially when using fresh embryo transfer IVF protocols.

Background: Polycystic ovary syndrome (PCOS)-related infertility remains a major challenge and the efficacy of conventional treatments is limited in certain patient groups and often fails to address the underlying causes of ovarian dysfunction. Platelet-rich plasma (PRP) is rich in growth factors and cytokines and has emerged as a potential regenerative therapy for women with a diminished ovarian reserve. Methods: A literature search for studies pertaining to intraovarian PRP administration and PCOS was performed on PubMed. Results: Preclinical studies in PCOS animal models have demonstrated that intraovarian PRP can improve folliculogenesis, enhance antioxidant defenses, normalize steroid hormone levels, and downregulate pro-apoptotic pathways. Early clinical reports suggest that intraovarian PRP may restore ovulation and improve ovarian reserve in women with long-standing amenorrhea and poor responses to standard fertility treatments. The proposed mechanisms of how PRP could improve folliculogenesis include the modulation of local ovarian gene expression, the activation of dormant follicles, angiogenesis, and a reduction in oxidative stress and inflammation. Conclusions: Although preliminary data are promising, larger studies are needed to establish the efficacy, if any, of intraovarian PRP administration as a potential novel therapeutic adjunct in women with PCOS.

Women with polycystic ovary syndrome (PCOS) and insulin resistance (IR) commonly have elevated serum advanced glycation end-products (AGEs) that accumulate in their ovaries, potentially altering ovarian function. AGEs have been shown to interfere with insulin signaling in granulosa cells (GCs) by suppressing the translocation of glucose transporters. Additionally, PCOS has been associated with insulin receptor substrate (IRS)-1 polymorphisms and upregulation in IRS-1 gene expression in GCs. We hypothesize that AGEs are partly responsible for ovarian IR by altering IRS-1 in human GCs. Cumulus granulosa cells from women undergoing IVF were cultured in control media or media containing human glycated albumin (HGA) as a source of AGEs. The quantification of mRNA expression was compared using RT-PCR for receptors for AGEs (RAGE), IRS-1, IRS-2, Glucose Transporter Type (GLUT)-1, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). In addition, IRS-1 protein intensity was assessed by immunofluorescence. Compared to the control group, HGA-treated GCs showed a statistically significant upregulation in RAGE mRNA by 314% and in IRS-1 mRNA by 423%. Even though there was a 183% increase in GLUT-1 mRNA, it did not reach statistical significance. There was no change in IRS-2 or NF-κB mRNA expression levels. Immunofluorescence showed that IRS-1 deposition was visualized in GCs, and the addition of HGA resulted in a significant increase in the intensity of IRS-1 protein compared to control cells. The AGE-induced upregulation in IRS-1, the primary insulin receptor substrate, in GCs could indicate compensation for insulin action deficiency and potentially IR. Additionally, immunofluorescence analysis of GLUT-4 revealed a statistically significant reduction in cytoplasmic GLUT-4 signal in HGA-treated GCs compared to controls (2.10 ± 0.21 vs. 3.81 ± 0.22 arbitrary units; p = 0.010), consistent with AGE-mediated disruption of glucose transporter localization. These results suggest that AGE exposure may initiate early molecular changes consistent with altered insulin signaling, but do not establish insulin resistance per se.

Advanced glycation end products (AGEs), a heterogenous group of products formed by the reaction between protein and reducing sugars, can form endogenously due to non-enzymatic reactions or by exogenous sources such as diet where considerable increase in AGEs is observed due to the modification of food mainly by thermal processing. Recent studies have suggested that AGEs could impact, via inducing inflammation and oxidative stress, the reproductive health and fertility in both males and females. This review presents a summary of recently published data pertaining to the pathogenesis of dietary AGEs and their receptors as well as their potential impact on female reproductive health. More specifically, it will present data pertaining to dietary AGEs’ involvement in the mechanistic pathogenesis of polycystic ovary syndrome, ovarian dysfunction, as well as the AGEs’ effect perinatally on the female offspring reproduction. Understanding the mechanistic impact of dietary AGEs on female reproduction can help contribute to the development of targeted pharmacological therapies that will help curb rising female infertility.

The injectable glucagon-like peptide-1 (GLP-1) receptor agonist (RA) drugs are commonly used for weight loss among reproductive-aged women but the perception of their impact on fertility is not clear among the public. The purpose of this review was to compare scientific literature to social media discourse and online search pertaining to the potential impact of GLP-1 RAs on female fertility. Group 1 included 3 social media platforms, each of which required a different data collection method. For Reddit, VADER (Communalytic ®) was used as a sentiment analyzer and for Twitter and TikTok, we performed a manual search for posts and scored them using an objective internal scale. Group 2 included the online search engine Google Trends. Group 3 consisted of medical literature search by PubMed. All sentiments of posts/comments/articles were graded as: \"Positive, Neutral, or Negative\" and compared among groups. In Groups 1 and 2, scores showed a significantly more Positive than Neutral, and more Neutral than Negative sentiments. In Group 3, among the 52 original studies found on PubMed in women with polycystic ovary syndrome (PCOS), they all had Positive sentiments. In Groups 1, 2, and 3, there was a strong positive correlation among all sentiments (r2 = 0.83). Even though all 3 social media platforms had the majority of posts with a Positive sentiment and correlated with Google Trends posts and with PubMed studies in women with PCOS (r2 = 0.74), there was a lack of PubMed studies pertaining to the effect of GLP-1 RA in women without PCOS. The Positive sentiments among women without PCOS is not justified by evidence-based medicine and there is a clear need for studies pertaining to this topic.

Background Besides being a risk factor for multiple metabolic disorders, obesity could affect female reproduction. While increased adiposity is associated with hormonal changes that could disrupt the function of the hypothalamus and the pituitary, compelling data suggest that obesity-related hormonal and inflammatory changes could directly impact ovarian function. Objective To review the available data related to the mechanisms by which obesity, and its associated hormonal and inflammatory changes, could affect the female reproductive function with a focus on the hypothalamic-pituitary-ovarian (HPO) axis. Methods PubMed database search for publications in English language until October 2017 pertaining to obesity and female reproductive function was performed. Results The obesity-related changes in hormone levels, in particular leptin, adiponectin, ghrelin, neuropeptide Y and agouti-related protein, are associated with reproductive dysfunction at both the hypothalamic-pituitary and the ovarian levels. The pro-inflammatory molecules advanced glycation end products (AGEs) and monocyte chemotactic protein-1 (MCP-1) are emerging as relatively new players in the pathophysiology of obesity-related ovarian dysfunction. Conclusion There is an intricate crosstalk between the adipose tissue and the inflammatory system with the HPO axis function. Understanding the mechanisms behind this crosstalk could lead to potential therapies for the common obesity-related reproductive dysfunction.

Background Women with PCOS have elevated levels of the harmful Advanced Glycation End Products (AGEs), which are highly reactive molecules formed after glycation of lipids and proteins. Additionally, AGEs accumulate in the ovaries of women with PCOS potentially contributing to the well-documented abnormal steroidogenesis and folliculogenesis. Main body A systematic review of articles and abstracts available in PubMed was conducted and presented in a systemic manner. This article reports changes in steroidogenic enzyme activity in granulosa and theca cells in PCOS and PCOS-models. It also described the changes in AGEs and their receptors in the ovaries of women with PCOS and presents the underlying mechanism(s) whereby AGEs could be responsible for the PCOS-related changes in granulosa and theca cell function thus adversely impacting steroidogenesis and follicular development. AGEs are associated with hyperandrogenism in PCOS possibly by altering the activity of various enzymes such as cholesterol side-chain cleavage enzyme cytochrome P450, steroidogenic acute regulatory protein, 17α-hydroxylase, and 3β-hydroxysteroid dehydrogenase. AGEs also affect luteinizing hormone receptor and anti-Mullerian hormone receptor expression as well as their signaling pathways in granulosa cells. Conclusions A better understanding of how AGEs alter granulosa and theca cell function is likely to contribute meaningfully to a conceptual framework whereby new interventions to prevent and/or treat ovarian dysfunction in PCOS can ultimately be developed.

PurposePlatelet-rich plasma (PRP) therapy has been used as an adjunct to fertility treatments in women with very low ovarian reserve and premature ovarian insufficiency. Recent literature in both humans and animals suggest that intraovarian PRP administration in the setting of poor ovarian reserve may help ovarian function and increase the chances of pregnancy.MethodsA comprehensive literature search through PubMed, MEDLINE databases, and recent abstracts published at relevant society meetings was performed and resulted in 25 articles and 2 abstracts published that studied effect of PRP on the ovaries for the purpose of reproduction.ResultsThis review article presents all the data published to date pertaining to intraovarian PRP injection and pregnancy, both naturally and after in vitro fertilization. It also presents the most recent data on the use of ovarian PRP in in vitro and animal model studies highlighting the possible mechanisms by which PRP could impact ovarian function.ConclusionsEven though recent commentaries questioned the use of PRP as an “add-on” therapy in fertility treatment because it has not been thoroughly studied, the recent basic science studies presented here could increase awareness for considering more serious research into the efficacy of PRP as an adjunct for women with poor ovarian reserve, premature ovarian insufficiency, and even early menopause who are trying to conceive using their own oocytes. Given its low-risk profile, the hypothetical benefit of PRP treatment needs to be studied with larger randomized controlled trials.

A mounting body of the literature suggests that environmental chemicals found in food and water could affect female reproduction. Many worldwide daily-used products have been shown to contain chemicals that could incur adverse reproductive outcomes in the perinatal/neonatal periods, childhood, adolescence, and even adulthood. The potential impact of Bisphenol A (BPA), Phthalates and Perfluoroalkyl substances (PFAS) on female reproduction, in particular on puberty, PCOS pathogenesis, infertility, ovarian function, endometriosis, and recurrent pregnancy loss, in both humans and animals, will be discussed in this report in order to provide greater clinician and public awareness about the potential consequences of these chemicals. The effects of these substances could interfere with hormone biosynthesis/action and could potentially be transmitted to further generations. Thus proper education about these chemicals can help individuals decide to limit exposure, ultimately alleviating the risk on future generations.

In the last decade, data has suggested that dietary advanced glycation end products (AGEs) play an important role in both reproductive and metabolic dysfunctions associated with polycystic ovary syndrome (PCOS). AGEs are highly reactive molecules that are formed by the non-enzymatic glycation process between reducing sugars and proteins, lipids, or nucleic acids. They can be formed endogenously under normal metabolic conditions or under abnormal situations such as diabetes, renal disease, and other inflammatory disorders. Bodily AGEs can also accumulate from exogenous dietary sources particularly when ingested food is cooked and processed under high-temperature conditions, such as frying, baking, or grilling. Women with PCOS have elevated levels of serum AGEs that are associated with insulin resistance and obesity and that leads to a high deposition of AGEs in the ovarian tissue causing anovulation and hyperandrogenism. This review will describe new data relevant to the role of AGEs in several key elements of PCOS phenotype and pathophysiology. Those elements include ovarian dysfunction, hyperandrogenemia, insulin resistance, and obesity. The literature findings to date suggest that targeting AGEs and their cellular actions could represent a novel approach to treating PCOS symptoms.