Elagolix Represents a Less Invasive and Cheaper Option than Injectable GnRH Antagonist for Ovulation Suppression in IVF.

BACKGROUND: The injectable GnRH antagonists have traditionally been used for ovulation suppression during controlled ovarian hyperstimulation in 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: A retrospective cohort study of patients undergoing IVF received either oral elagolix 50 mg every other day or ganirelix/cetrotide injection daily for ovulation suppression during controlled ovarian hyperstimulation. A total of 269 patients, 173 in the elagolix group and 96 in the ganirelix/cetrotide group, were included. The main outcome was the suppression of luteinizing hormone (LH) blood levels reflecting ovulation suppression. RESULTS: The age, body mass index, AMH levels, baseline FSH, antral follicles count, the dose of medications used, the 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 the 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 the IVF cycle outcomes in both groups, the number of oocytes retrieved, the number of mature oocytes, the fertilization rate, the blastocyst formation rate, the euploidy rate and the endometrial lining thickness at the time of the trigger were all similar. CONCLUSIONS: 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.

Live Birth Following a Two-Way Transport In Vitro Fertilization Using a Portable Incubator: A Novel Protocol Executed During the COVID-19 Pandemic.

This case presents a live birth of a complete "two-way transport IVF" using a portable incubator during the COVID-19 pandemic, allowing the patient to undergo both oocyte collection and embryo transfer in a satellite office located 30 miles, 2-h drive, away from the central IVF laboratory. A 30-year-old patient who lives on Long Island NY, with a history of unexplained infertility and previously failed intra-uterine inseminations (IUI), had a telehealth consultation for IVF. Because of the high prevalence of the COVID-19 virus in Manhattan-NYC where the central IVF laboratory is located, the patient was consented to undergo a two-way transport IVF. She was initiated on a controlled ovarian superovulation protocol, after which follicular aspiration of 11 large follicles was performed in a regular examination room, under local vaginal anesthesia at the satellite office. The follicular fluid aspirates were collected in the usual tubes which were immediately sealed and placed inside a portable incubator. The sperm sample was also produced at the satellite location, washed, and placed in the same incubator. The aspirate tubes and the washed sperm were shipped immediately to the central laboratory. A total of ten oocytes were retrieved, out of which six were mature, leading to three good-quality blastocysts that were cryopreserved. The following month, the patient was prepared for a frozen embryo transfer (FET) cycle at the satellite location. On the day of the FET, two blastocysts were thawed and loaded in a transfer catheter in the central IVF laboratory. The catheter containing the embryos was shipped to the satellite location by an experienced embryologist using the portable incubator. The FET was performed in the same initial examination room. A singleton smooth pregnancy resulted from the FET, leading to the delivery of a healthy baby at term. This novel approach, learned during the pandemic, was able to alleviate the psychological, physical, and financial burdens on the patient, while also carrying the potential to reduce the costs of setting up an IVF laboratory, lowering prices and making IVF available to a larger portion of the population, especially when staffing IVF laboratories could be a major hurdle.

Intraovarian Platelet-rich Plasma Administration Induced Spontaneous Ovulation in an Anovulatory Woman With PCOS.

The use of platelet-rich plasma (PRP) has become popular as an adjunct to fertility treatment for women with infertility, particularly those with low ovarian reserve and premature ovarian insufficiency. Recent data in a polycystic ovary syndrome (PCOS) animal model demonstrated that intraovarian PRP administration improved folliculogenesis, ovarian antioxidant potential, and serum hormonal imbalance, suggesting that PRP could be considered a novel technique to alleviate PCOS-induced pathogenesis. With injection of PRP into the ovaries, it has been hypothesized that the infusion of cytokines and growth factors may exhibit a local effect that changes the expression of genes important in folliculogenesis and steroidogenesis, decreases inflammation, and partially restores normal ovarian function. This report is the first to present a case of a long-term amenorrheic woman with PCOS who has been trying to conceive, who resumed spontaneous ovulatory cycles, and had improvement in several aspects of her hormonal imbalance following intraovarian PRP administration. The purpose of this case report is to increase awareness regarding the possible benefits of intraovarian PRP injections for women with PCOS. There is a clear need for larger prospective studies to properly elucidate the effect of intraovarian PRP administration on both the reproductive and metabolic dysfunctions observed in women with PCOS.

Ozone sauna therapy and pulsed electromagnetic field therapy could potentially improve outcome in women with diminished ovarian reserve undergoing assisted reproductive technology.

There are limited treatment options for women with severely diminished ovarian reserve (DOR) who experience repeatedly failed in vitro fertilization (IVF) cycles and with persistently thin endometrial lining thickness (EMT) during frozen embryo transfer cycles. Therefore, a large majority of patients resort to using donor oocytes and gestational carriers. Data from existing animal and human studies suggest that ozone sauna therapy (OST) and pulsed electromagnetic field therapy (PEMF) are emerging as potential therapeutic adjuncts for female reproduction. This study was conducted to assess the fertility outcome of OST + PEMF in vivo in patients undergoing IVF/frozen embryo transfe and the effects of OST in vitro on human granulosa cell (GC) function. Forty-four women with DOR underwent their 1st IVF cycle (Cycle 1), and then were administered transdermal and intravaginal OST + PEMF, twice a week for 3 weeks, followed by a 2nd IVF cycle (Cycle 2) using the same protocol as in Cycle 1. GCs collected from another six women who underwent egg retrieval were equally split and cultured with OST (test) or placed in room temperature (control) outside the OST chamber in the same room. The results demonstrated that Cycles 1 and 2 had no significant difference in the number of days of stimulation, baseline hormones measured, number of oocytes retrieved or peak estradiol levels. However, the number of embryos formed after OST + PEMF in Cycle 2 was significantly higher than the Cycle 1. Furthermore, EMT measured in Cycle 2 demonstrated a significant increase compared to Cycle 1 and all patients reached a satisfactory EMT of approximately 7 mm. In vitro studies demonstrated that OST led to a 5-fold significant increase in the aromatase enzyme while a significant 50% reduction was noted in the side-chain cleavage enzyme in GCs. Both OST + PEMF are known for their vasodilatory, anti-inflammatory, and antioxidant actions, which could enhance endometrial receptivity and increase the number of formed embryos without increasing the number of oocytes retrieved, suggesting an improvement in oocyte quality. Finally, ozone can alter genes involved in steroidogenesis suggesting that it could improve ovarian function.

Ozone Sauna Therapy (OST) and Pulsed Electromagnetic Field Therapy (PEMF) delivered via the HOCATT machine could improve endometriosis pain along with lowering serum inflammatory markers.

PROBLEM: Endometriosis, a common and challenging condition, is a pelvic inflammatory condition that causes chronic pelvic pain (CPP) and infertility. Even though standard medical therapies and surgeries can help CPP, a large percentage of women remain symptomatic following the conventional treatments. Thus, there is a need to study new non-traditional therapeutic adjuncts in this patient population to improve their quality of life. One non-traditional therapeutic agent is Ozone Sauna Therapy (OST) which has been shown to have an anti-inflammatory action, but no studies have been performed to assess the efficacy of OST in women with endometriosis suffering with CPP. Another non-traditional therapeutic agent is Pulsed Electromagnetic Field Therapy (PEMF) where one small pilot study has shown that PEMF exposure to women with endometriosis and pelvic pain showed dramatic relief in symptoms. METHOD OF STUDY: The HOCATT machine, by delivering a combination of both OST and PEMF in one machine, has been shown to improve fertility treatment outcome via in vitro fertilization (IVF) in older women by potentially improving oocyte quality. This study was conducted to assess the effect of the HOCATT machine use on the pain scale in patients struggling with CPP due to endometriosis. In the first study, eight women with endometriosis were administered transdermal and intravaginal OST + PEMF, twice a week for 3 weeks (total of 6 sessions). Once a week, the participants were asked to fill a pain scale. In the second study, 10 women were recruited in order to evaluate the changes in serum inflammatory markers following OST + PEMF exposure after 3-week period using the HOCATT machine twice a week (total of 6 sessions). RESULTS: The participants had a mean age of 39.7 ± 1.1 years. The results showed a significant improvement in pain scale following the fourth session (p < .05) and a significant drop in serum levels of the inflammatory markers CRP (p = .0438) and IL-1ß (p = .0031) and a significant increase in serum levels of IL-8 (p = .033). CONCLUSIONS: This pilot study suggests that a combination of OST and PEMF using the HOCATT machine could potentially represent potential therapeutic adjuncts for women with inflammatory disorders such as endometriosis. There is a definite need for larger cohort studies and even randomized trials in order to better assess the efficacy of OST and PEMF in women with other inflammatory disorders.

Intraovarian platelet-rich plasma administration could improve blastocyst euploidy rates in women undergoing in vitro fertilization.

OBJECTIVE: Platelet-rich plasma (PRP) therapy has received a considerable attention as an adjunct to fertility treatments, especially in women with very low ovarian reserve and premature ovarian insufficiency. Although recent studies have demonstrated that PRP led to improvements in folliculogenesis and biomarkers of ovarian reserve, the effect of intraovarian PRP administration on embryo genetics has not been studied. METHODS: We report a pilot study of patients who had preimplantation genetic testing for aneuploidy (PGT-A) before and then within 3 months following PRP administration. Twelve infertile women with at least one prior failed in vitro fertilization (IVF) cycle underwent ovarian stimulation (cycle 1) with a gentle stimulation protocol and PGT-A performed at the blastocyst stage. Following cycle 1, autologous intraovarian PRP administration was performed. Within 3 months following PRP administration, the patients underwent cycle 2 and produced blastocysts for PGT-A. The percentage of euploid embryos between both cycles was compared. RESULTS: The mean age of all participants was 40.08±1.46 years, and their mean body mass index was 26.18±1.18 kg/m2. The number of good-quality embryos formed at the blastocyst stage was similar between cycle 1 and cycle 2 (3.08±0.88 vs. 2.17±0.49, respectively; p=0.11). Among all patients in cycle 1, 3 of 37 embryos were euploid (8.11%) while in cycle 2, 11 out of 28 embryos were euploid (39.28%, p=0.002). Three clinical pregnancies were noted among this patient group. CONCLUSION: This novel study is the first to present an improvement in the embryo euploidy rate following intraovarian PRP application in infertile women with prior failed IVF cycles. The growth factors present in PRP may exhibit a local paracrine effect that could improve meiotic aberrations in human oocytes and thus improve euploidy rates. Whether PRP improves live birth rates and lowers miscarriage rates remains to be determined in large trials.

Contribution of Advanced Glycation End Products to PCOS Key Elements: A Narrative Review.

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.

A Case of Asthenozoospermia Following COVID-19 Infection.

PURPOSE: Studies pertaining to the effect of COVID-19 infection on male fertility are scarce. This case report describes a case of transient asthenozoospermia, absence of sperm motility, following a moderately severe COVID-19 infection. CASE: A couple presenting for infertility treatment due to low ovarian reserve presented for their second intrauterine insemination (IUI). Their first IUI was performed 1 month earlier when the semen parameters were normal. A couple of weeks before the second IUI, the unvaccinated 48-year-old male partner contracted COVID-19 and was admitted to the hospital for several days. He received IV Remdesivir and continuous oxygen by nasal cannula. His hospitalization did not require intubation or intensive care unit admission. He was discharged after 12 days of hospitalization without home oxygen treatment. On the day of the second IUI, the semen analysis showed a normal sperm count with 0% motility. Three months following his COVID-19 diagnosis, a repeat semen analysis showed restored normal parameters with more than 40% motility. CONCLUSION: This aim of this report is to increase awareness that moderate COVID-19 requiring hospitalization could affect, though temporarily, sperm motility and should be considered in the differential diagnosis when male infertility is encountered.

Postnatal weaning to different diets leads to different reproductive phenotypes in female offspring following perinatal exposure to high levels of dietary advanced glycation end products.

OBJECTIVE: To examine, following perinatal exposure to a diet high in advanced glycation end products (AGEs), whether the use of standard AGE-free mouse chow during the postweaning period alters metabolism and reproduction differently than exposure to a diet low in AGEs. DESIGN: Experimental animal study. SETTING: University-based research laboratory. ANIMAL(S): Female CD1 mice. INTERVENTION(S): Seven-week-old mice were placed on a diet either low or high in AGEs perinatally, before mating and then during pregnancy and lactation. All offspring were weaned onto an AGE-free normal chow. MAIN OUTCOME MEASURE(S): Growth curve, liver and abdominal fat weight, insulin and glucose tolerance tests, vaginal opening, estrous cyclicity, and serum levels of antimüllerian hormone, leptin, and adiponectin were assessed. Ovarian histologic examination for follicular count and gene expression was also performed. RESULT(S): Compared with the mice exposed to a diet low in AGEs, the mice exposed to a diet high in AGEs showed lower body weight in pups, lower liver weight, delayed vaginal opening, higher serum antimüllerian hormone levels, lower primordial and secondary follicle pools, and higher ovarian Fshr messenger RNA levels. CONCLUSION(S): Following weaning, perinatal AGEs can target puberty onset and folliculogenesis differently to standard mouse chow.

Impact of Dietary Advanced Glycation End Products on Female Reproduction: Review of Potential Mechanistic Pathways.

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.

Ovarian response to intraovarian platelet-rich plasma (PRP) administration: hypotheses and potential mechanisms of action.

PURPOSE: Platelet-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. METHODS: A 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. RESULTS: This 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. CONCLUSIONS: Even 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.

Intraovarian PRP Injection Improved Hot Flashes in a Woman With Very Low Ovarian Reserve.

PRP, rich in growth factors and cytokines, has been gaining considerable attention as an adjunct therapy to fertility treatment for women with very low ovarian reserve and premature ovarian insufficiency. To date, most prior studies have focused on the effect of PRP on ovarian response pertaining to oocyte production and pregnancy outcome following assisted reproductive technology. This report presents a patient with very low ovarian reserve, with medical problems that preclude her from taking hormone replacement therapy, who presented for fertility treatment with PRP and then accidentally reported significant improvement of menopausal symptoms including her hot flashes for 14 weeks following PRP intra-ovarian injection. The purpose of this case report is to increase awareness of clinicians about the use of PRP as a potential alternative therapy for hot flashes in women who have contraindications for hormone replacement therapy.

Use of Intra-uterine Injection of Platelet-rich Plasma (PRP) for Endometrial Receptivity and Thickness: a Literature Review of the Mechanisms of Action.

Endometrial receptivity and thickness play an important role in achieving a pregnancy. Intrauterine autologous platelet-rich plasma (PRP) infusion has been used in infertile women with recurrent implantation failure (RIF) and thin endometrial lining thickness (EMT). Literature search was performed in PubMed for studies including in vitro, animal, and human studies as well as in abstracts presented at national conferences. Animal studies demonstrated a decrease in the expression of inflammatory markers and fibrosis, and increased endometrial proliferation rate, increased expression of proliferative genes, and increased pregnancy rates. The in vitro studies showed that PRP was associated with increased stromal and mesenchymal cell proliferation, increased expression of regenerative enzymes, and enhancement in cell migration. In infertile women undergoing assisted reproductive technology, one randomized clinical trial showed that PRP intrauterine infusion improved EMT, implantation rate, and clinical pregnancy rate (CPR) in patients with thin EMT, while 3 other trials involving subjects with RIF showed conflicting results related to CPR. Case series and cohort studies showed conflicting results pertaining to CPR. Data to date suggest that PRP may be beneficial in improving endometrial thickness and endometrial receptivity. However, further large prospective and high-quality trials are needed to assert its effect and to identify the population of patients that would benefit the most.

Perinatal exposure to high dietary advanced glycation end products affects the reproductive system in female offspring in mice.

Maternal nutrition and the intrauterine environment are important in determining susceptibility to reproductive and metabolic disturbances. Advanced glycation end products (AGEs) are widely consumed in Western diet. The purpose of this study was to determine whether perinatal exposure to a high levels of dietary AGEs affect metabolic and reproductive parameters in female mice offspring. Female CD1 mice, 7 weeks old, were placed on either a diet low (L-AGE) or high (H-AGE) in AGEs before mating and then during pregnancy and lactation. All offspring were weaned onto the L-AGE diet and studied through to 16 weeks of age; they were counted and weighed at birth and then every week for a total of 11 weeks. Vaginal opening, litter size, growth curve, liver and abdominal fat weights, serum levels of anti-Mullerian hormone, leptin and adiponectin, as well as insulin and glucose tolerance tests were compared. Ovaries were harvested for follicular count and gene expression by real-time polymerase chain reaction. Compared to perinatal exposure to the L-AGE diet, perinatal exposure to the H-AGE diet caused lower body weight at birth, and adult offspring exhibited delayed growth, lower serum leptin and adiponectin levels, delayed vaginal opening, irregular oestrous cyclicity, arrested follicular development and significant alterations in the expression of genes involved in folliculogenesis (Amh and Amhr2) and steroidogenesis (Cyp19a1). These results indicate that perinatal exposure to a diet elevated in AGEs causes deficits in perinatal growth, pubertal onset, and reproductive organ development in female mice. Whether these findings translate to humans remains to be determined in future studies.

Monocyte chemotactic protein-1 plays a role in ovarian dysfunction related to high-fat diet-induced obesity.

Obesity, known to cause a systemic elevation in monocyte chemotactic protein-1 (MCP-1), adversely affects normal ovarian function. The aim of this study was to determine whether MCP-1 plays a role in ovarian dysfunction that is related to obesity induced by high-fat (HF) diet intake. Wild type (WT) C57BL/6J mice were fed either normal chow (NC) (Group 1, control group) or HF diet (Group 2). To assess whether MCP-1 is involved in HF-diet-induced ovarian dysfunction, MCP-1 knock-out mice were fed HF diet (Group 3). Body weight, body fat composition, number of oocytes collected following ovarian superovulation with gonadotropins, ovarian macrophage markers and expression of genes important in folliculogenesis and steroidogenesis were quantified in the 3 groups of animals. Animals in Group 2 gained significant body weight and body mass, produced the fewest number of oocytes following superovulation, and had significant alterations in ovarian genes involved in folliculogenesis and steroidogenesis as well as genes involved in inflammation. Although animals in Group 3 had the highest body weight and body fat composition, they produced similar number of oocytes compared to animals in Group 1 but had different ovarian gene expression compared to Group 2. These findings suggest that MCP-1 gene knockout could reverse some of the adverse effects of obesity induced by HF diet intake. Future studies assessing ovarian histology in MCP-1 knock out mouse model will confirm our findings. MCP-1 inhibition could represent a future therapeutic target to protect ovarian health from the adverse effects of HF diet ingestion.

Dietary Advanced Glycation End Products (AGEs) could alter ovarian function in mice.

Nutrition is an important source of exogenous AGEs and thermally processed foods present in western-style diets contain a large amount of these pro-inflammatory AGEs. Additionally, the intake of dietary AGEs could upregulate ovarian gene expression of inflammatory macrophage markers. The objective of this study was to investigate the effect of diet rich in AGEs on estrous cyclicity and ovarian function in a mouse model. Six-week old C57BL/6 J female mice were randomly subjected to either a diet low in AGEs (L-AGE) or a diet high in AGEs (H-AGE) for a total of 13 weeks. Experiments performed included daily vaginal smears to assess estrous cyclicity, ovarian superovulation with gonadotropins to assess the number of oocytes released, whole ovarian tissue mRNA quantification by RT-PCR to quantify genes involved in folliculogenesis, steroidogenesis, and macrophage markers, and ovarian morphology for follicle count. Outcome measures included estrous cyclicity, number of oocytes following superovulation, expression of genes involved in folliculogenesis, steroidogenesis, and macrophage infiltration as well as the number of primordial, primary, secondary, antral follicles and corpora lutea. Compared to mice on L-AGE diet, mice on H-AGE spent significantly longer time in the diestrus phase, had similar number of oocytes released following ovarian superovulation, and showed significant alterations in genes involved in steroidogenesis (increase in Star mRNA expression levels) and folliculogenesis (increase in Gdf-9 and Fshr mRNA expression levels). Mouse macrophage marker F4/80 mRNA expression was upregulated in mice on H-AGE diet compared to mice on L-AGE diet. Finally, mice on H-AGE diet had significantly fewer corpora lutea in their ovaries. These results indicate that the ingestion of high amounts of dietary AGEs could disrupt folliculogenesis and steroidogenesis that might lead to abnormal estrous cyclicity. Intake of dietary AGEs could also upregulate ovarian gene expression of inflammatory macrophage markers.

Ozone and pulsed electro-magnetic field therapies improve endometrial lining thickness in frozen embryo transfer cycles: Three case reports.

RATIONALE: In assisted reproductive technology, a persistently thin endometrial lining represents a huge challenge during frozen embryo transfer (FET) cycles. PATIENT CONCERNS: Three patients who had a persistently thin endometrial lining despite the use of several medical agents known to improve endometrial lining thickness. DIAGNOSES: Infertility undergoing FET cycles. INTERVENTIONS: A combination of transdermal and intravaginal ozone therapy along with Pulsed Electro-Magnetic Field (PEMF) therapy. OUTCOMES: Ozone with PEMF, both of which are known to have vasodilatatory, anti-inflammatory, and anti-oxidant actions, were successful in improving the thickness of the endometrial lining in all 3 patients. Two out of 3 patients became pregnant following single embryo transfer. LESSONS: Ozone with PEMF constitute a novel experimental approach for women with persistently thin endometrial lining undergoing FET. This novel approach needs validation by large well-designed studies.

Role of adiponectin in ovarian follicular development and ovarian reserve.

Adiponectin levels are associated with anti-Müllerian hormone (AMH) and kisspeptin levels in non-ovarian tissues. The objective of the present study was to investigate the association between adiponectin and the genes important for ovarian follicular development and ovarian reserve, specifically AMH and kisspeptin, and their corresponding receptors. In the first experiment, the mRNA levels of anti-Müllerian hormone (amh) and its receptor (Amhr2), as well as those of kisspeptin (Kiss1) and its receptor (Kiss1r), were quantified by reverse transcription-polymerase chain reaction analysis in the ovaries of two groups of mice [adiponectin-knockout (KO) vs. control] that underwent oophorectomy. The second experiment measured follicular phase serum AMH and follicular fluid adiponectin levels in 25 women who underwent controlled ovarian hyperstimulation for in vitro fertilization. Compared with the control mice, adiponectin-KO mice had 6.5 times lower Kiss1 mRNA levels (P=0.009) and a tendency for lower ovarian Kiss1r mRNA expression levels (P=0.06). However, adiponectin-KO mice had significantly higher Amhr2 mRNA levels (P=0.01). In all women participants, there was a positive correlation between serum AMH and follicular fluid adiponectin concentrations (r=0.54, P=0.006). The findings of the present study indicate that adiponectin may play a role in ovarian physiology through its impact on genes crucial for ovarian follicular development and ovarian reserve, such as kisspeptin and AMH. Understanding the role of adiponectin in ovarian function may improve our knowledge of the pathophysiology underlying ovulatory dysfunction in obese women, who usually have low adiponectin levels, and overcome reproductive barriers.

Ozone therapy: a potential therapeutic adjunct for improving female reproductive health.

Ozone is emerging as a new adjunct therapeutic agent for female infertility. We here present a review of the literature, to date, pertaining to the effect of ozone therapy on tubal, ovarian, endometrial, and vaginal factors that could potentially affect female fertility. It also presents data pertaining to the relationship of ozone therapy on pelvic adhesion formation. Most data were performed on animals and very few human studies existed in the literature. Results suggested that ozone therapy could have beneficial effect on tubal occlusion, could protect from endometritis and vaginitis, might protect ovaries from ischemia and oocyte loss and finally might lead to less formation of pelvic adhesions. There is a critical need for human studies pertaining to ozone therapy, especially using safe methods of administration, such as transdermally or intravaginally, on female fertility.