Inflammation and Oral Contraceptive Use in Female Athletes Before the Rio Olympic Games

Abstract: This study investigated the association between synthetic ovarian hormone use [i.e., the oral contraceptive (OC) pill] and basal C-reactive protein (CRP), peripheral blood immune cell subsets, and circulating pro- and anti-inflammatory cytokine concentrations in elite female athletes. Elite female athletes (n = 53) selected in Rio Summer Olympic squads participated in this study; 25 were taking an OC (AthletesOC) and 28 were naturally hormonally cycling (AthletesNC). Venous blood samples were collected at rest for the determination of sex hormones, cortisol, CRP, peripheral blood mononuclear memory and naïve CD4+ T-cells, CD8+ T-cells and natural killer cells, as well as pro- and anti-inflammatory cytokine concentrations. C-reactive protein concentrations were elevated (p < 0.001) in AthletesOC (median = 2.02, IQR = 3.15) compared to AthletesNC (median = 0.57, IQR = 1.07). No differences were reported for cortisol, cytokines, or PBMC immune cell subsets, although there was a trend (p = 0.062) for higher IL-6 concentrations in AthletesNC. Female Olympians had substantially higher CRP concentrations, a marker of inflammation and tissue damage, before the Rio Olympic Games if they used an OC. Future research should examine the potential consequences for athlete performance/recovery so that, if necessary, practitioners can implement prevention programs.


The central role of ovulatory disturbances in the etiology of androgenic polycystic ovary syndrome (PCOS)—Evidence for treatment with cyclic progesterone

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Sonia Shirin

University of British Columbia, Vancouver, BC, Canada


Menstrual cycle phases and exposure to environmental contaminants : Menstrual Cycle and Ovulation Study 2 (MOS2)

X. CM

University of Electronic Science and Technology of China

Abstract: In 2006-2008, 610 premenopausal, spontaneously menstruating women in the Metro Vancouver region participated in a Canadian Institutes of Health Research (CIHR)-funded singlecycle in which they collected first morning urine specimens for estrogen and progesterone metabolites1. Following that study, after analyses, we retrieved the remaining urine specimens from the analyzing laboratory (University of Washington). We sorted data so that samples from all those women who were anovulatory by the two combined urinary steroid evaluation methods2,3, plus from those who were ovulatory with the highest and the lowest urinary hormone values were shipped to Health Canada (HC) via Dr. Warren Foster’s laboratory at McMaster University. Those data on flame retardant contaminants in women’s urine have been published4, but the cycle-phase specific data are still in analysis (personal communication, S Kalyan, 2019). In 2017, HC basic scientists launched applications to HC to fund a similar study to assess flame retardant excretory changes in the same population/locale 10 years later. This application was funded in 2018 at Health Canada with Dr. JC Prior as a collaborator. Extensive negotiations by CeMCOR and HC scientists ensued about funding the process of obtaining these follow-up specimens. CeMCOR managed to obtain a HC agreement to fund the minimal cost of recruiting, training and obtaining two menstrual phase-specific urine specimens from 250 Metro Vancouver women. Because of the lack of a progesterone threshold for ovulation, we will collect one follicular and one luteal/premenstrual urine sample per woman. However, this time we will better characterize the ovulatory cycle using a validated quantitative basal temperature method5,6 that can assess luteal phase length as well as the presence/absence of evidence for ovulation. In addition we will collect serial salivary progesterone and estradiol values measured by the state-of-the-art sensitive and specific tandem mass spectrometry (LC-MS/MS) methods7 to use as the gold standard for an ovulatory cycle. There is increasing evidence that many variables differ across women’s two main menstrual cycle phases: follicular and luteal7-10. These real and potential differences in metabolism may alter the susceptibility of women to environment exposures, and also could change their urinary elimination. Those are the root reasons for doing this study.


Low-dose naltrexone as a treatment for chronic fatigue syndrome

Abstract: Naltrexone is used as an off-label treatment in low doses for several chronic immune-modulated disorders in many countries. Although only small-scale clinical trials have been performed, these suggest efficacy in several diseases including Crohn’s disease, fibromyalgia and Gulf War Illness. Despite numerous internet reports of response to low-dose naltrexone (LDN), no clinical trials exist in people with chronic fatigue syndrome. This condition is characterised by chronic profound fatigue, postexertional malaise, pain and autonomic and neurocognitive disturbances. This series of three case reports compiled by people with long-term ill-health due to chronic fatigue syndrome shows the range of responses they observed when taking LDN, from life changing to a reduction in some symptoms only. Treatment doses ranged from 4 to 12 mg. Clinical trials may be warranted to explore the potential use of naltrexone in people with these debilitating illnesses which currently have no licensed treatments available.


Reproductive capacity and recurrence of disease after surgery for moderate and severe endometriosis - a retrospective single center analysis

Abstract: Background Endometriosis can be associated with considerable pain and sterility. After surgical excision of moderate or severe endometriosis lesions, the rate of recurrence reaches up to 67%. The objective of this retrospective study was to establish the recurrence and pregnancy rates following surgical resection of stage III/IV endometriosis lesions. Indications for operation were endometriosis symptoms, sonographic findings and/or infertility. Methods A total of 456 patients who underwent stage III/IV endometriosis surgery between 2004 and 2014 were sent a questionnaire relating to their postoperative medical treatment, pregnancies, relief of symptoms and recurrence. Responses of 206 patients (45.2%) and their clinical data were analysed for this study. Results A total of 66.5% ( N = 137) of patients had stage III disease, and 33.5% ( N = 69) had stage IV disease. The average age was 37 years (17–59). A total of 63.1% ( N = 130) of surgeries were performed by laparoscopy, 21.8% ( N = 45) were performed by laparotomy and 15% ( N = 31) were performed by conversion. Complete resection of endometriosis lesions was achieved in 90.8% of patients ( N = 187). After surgery, 48.5% ( N = 100) of the women did not receive hormonal treatment; the main reason was the desire for children in 53%. Complete or partial relief in complaints was achieved in 93.2% ( N = 192). The rate of recurrence was 21.8% ( N = 45). The statistically significant factors that was associated with a higher risk to develop recurrence was an age < 35 ( p < 0.005). After surgery, 65.8% (79/120) of patients who wished to have children became pregnant. There was a statistically significant association among a higher postoperative pregnancy rate and age < 35 ( p < 0.003) in multivariate logistic regression analysis and laparoscopic surgical access in univariate logistic regression analysis ( p < 0.01). Conclusion We assessed the high percentage of complete or partial relief of symptoms of 93.2%, the high postoperative pregnancy rate of 65.8% and the low rate of recurrence of 21.8% compared to international literature to be very encouraging for women suffering from moderate and severe endometriosis. Though laparoscopy is considered the ‘gold standard’of endometriosis surgery, laparotomy still may be indicated in patients with extensive endometriosis especially to preserve reproductive function.


Balanced actions of estradiol and progesterone—A new paradigm of women’s reproductive health


DIR Jahrbuch 2019 (Deutsches IVF-Register Annual Report 2019)

Abstract: Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2019. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).


Effects of Moral Fonts on Action and Decision Making

Abstract: This landmark publication is in its second edition has been completely revised and updated to reflect recent developments in magisterial teaching and scientific research. More than thirty authors, who are experts in their fields, examine moral action theory, key ethical principles, ethics committees, the embryo and fetus, contraception, reproductive technologies, difficult pregnancies, rape protocols, the determination of death, palliative care, nutrition and hydration, the persistent vegetative state, do-not-resuscitate orders, health care proxies, organ donation, vaccination refusals, genetic medicine, human experimentation, religious freedom, triage, cooperation with evil, state mandates, organizational ethics, and other topics. Catholic Health Care Ethics is an ideal resource for classroom use in colleges and universities, as well as in nursing schools and by ethics committees in hospitals and other health care facilities.


Sustainable Use of Nanomaterials in Textiles and Their Environmental Impact

Abstract: At present, nanotechnology is a priority in research in several nations due to its massive capability and financial impact. However, due to the uncertainties and abnormalities in shape, size, and chemical compositions, the existence of certain nanomaterials may lead to dangerous effects on the human health and environment. The present review includes the different advanced applications of nanomaterials in textiles industries, as well as their associated environmental and health risks. The four main textile industry fields using nanomaterials, nanofinishing, nanocoatings, nanofibers, and nanocomposites, are analyzed. Different functional textiles with nanomaterials are also briefly reviewed. Most textile materials are in direct and prolonged contact with our skin. Hence, the influence of carcinogenic and toxic substances that are available in textiles must be comprehensively examined. Proper recognition of the conceivable benefits and accidental hazards of nanomaterials to our surroundings is significant for pursuing its development in the forthcoming years. The conclusions of the current paper are anticipated to increase awareness on the possible influence of nanomaterial-containing textile wastes and the significance of better regulations in regards to the ultimate disposal of these wastes.


Long-term risk of de novo mental health conditions after hysterectomy with ovarian conservation: a cohort study

Abstract:
OBJECTIVE: The aim of this research was to study the long-term risk of de novo mental health conditions in women who underwent hysterectomy with bilateral ovarian conservation compared with age-matched referent women.

METHODS: Using the Rochester Epidemiology Project records-linkage system, we identified a historical cohort of 2,094 women who underwent hysterectomy with ovarian conservation for benign indications at age ≥18 years and with an index date between 1980 and 2002 in Olmsted County, Minnesota. Each woman was age-matched (±1 y) to a referent woman residing in the same county who had not undergone hysterectomy or any oophorectomy before the index date. These two cohorts were followed historically to identify de novo mental health conditions. We estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) using Cox proportional hazards models adjusted for 20 preexisting chronic conditions and other potential confounders. We also calculated absolute risk increases (ARIs) and reductions (ARRs) at 30 years of follow-up.

RESULTS: Over a median follow-up of 21.9 years, women who underwent hysterectomy at any age experienced increased risks of de novo depression (adjusted HR 1.26; 95% CI, 1.12-1.41; ARI 6.6%) and anxiety (adjusted HR 1.22; 95% CI, 1.08-1.38; ARI 4.7%). The association for depression increased significantly with younger age at hysterectomy, but did not vary significantly by indication. Interactions were not significant for anxiety.

CONCLUSIONS: Hysterectomy, even with ovarian conservation, is associated with an increased long-term risk of de novo depression and anxiety, especially when performed in women who are younger. : Video Summary:http://links.lww.com/MENO/A465.


NaProTechnology: A Medical Embodiment of the Catholic Perspective on an Infertile Couple’s Right to Family Planning

Renee Mirkes

Pontifical John Paul II Institute for Studies on Marriage and Family

Abstract: This article considers one question: How does the Catholic Church guide infertile couples to exercise their right to build a family? Part One examines the principal tenets of Catholic social teaching on human rights in general. Part Two focuses in particular on the Church’s guidelines regarding the right to family planning for infertile couples. And Part Three contrasts NaProTechnology protocols for infertility with in vitro fertilization and concludes that NaPro provides infertile couples not only a responsible means of conceiving a baby that remedies the injustice of in vitro fertilization but also a medical embodiment of the Church’s teaching on the right to family planning.

The National Catholic Bioethics Quarterly


Inositol Treatment for PCOS Should Be Science-Based and Not Arbitrary

Abstract: The aim of this paper is to critically analyze the composition of many inositol-based products currently used to treat Polycystic Ovary Syndrome (PCOS). Several different combinations of myo-inositol and D-chiro-inositol, with and without additional compounds such as micro- and macroelements, vitamins, and alpha-lipoic acid, have been formulated over the years. Such therapeutic proposals do not take various features of inositol stereoisomers into consideration. As an example, it is important to know that D-chiro-inositol treatment may be beneficial when administered in low doses, yet the progressive increase of its dosage results in the loss of its advantageous effects on the reproductive performance of women and a deterioration in the quality of blastocysts created via in vitro fertilization (IVF). In addition, we have to consider that the intestinal absorption of myo-inositol is reduced by the simultaneous administration of D-chiro-inositol since the two stereoisomers compete with each other for the same transporter that has similar affinity for each of them. A decrease in myo-inositol absorption is also found when it is coadministered with inhibitors of sugar intestinal absorption and/or types of sugars such as sorbitol, maltodextrin, and sucralose. The combination of these may require higher amounts of myo-inositol in order to reach a therapeutic dosage compared to inositol administration alone, a particularly important fact when physicians strive to obtain a specific plasma level of the stereoisomer. Finally, we must point out that D-chiro-inositol was found to be an aromatase inhibitor which increases androgens and may have harmful consequences for women. Therefore, the inositol supplements used in PCOS treatment must be carefully defined. Clinical evidence has demonstrated that the 40 : 1 ratio between myo-inositol and D-chiro-inositol is the optimal combination to restore ovulation in PCOS women. Therefore, it is quite surprising to find that inositol-based treatments for PCOS seem to be randomly chosen and are often combined with useless or even counterproductive molecules, all of which can weaken myo-inositol's efficacy. Such treatments clearly lack therapeutic rationale.


Women’s reproductive system as balanced estradiol and progesterone actions—a revolutionary, paradigm-shifting concept in women’s health

Abstract: This review is to challenge current concepts of women’s reproduction with its cultural over-emphasis on estrogen and positive actions, while progesterone tends to be ignored or associated with negative effects. To explore the physiology, and the clinical implications of understanding that progesterone and estradiol interact in counterbalancing and complementary ways within a complex system that is Women’s Reproductive Health. Fundamental, descriptive, quantitative and experimental data all show that estradiol’s important cellular action is to promote growth and proliferation; by contrast, despite short-term proliferative effects, progesterone’s dominant actions are to inhibit proliferation, to enhance differentiation and promote maturation. Estradiol and progesterone variably interact in every cell and tissue in women’s bodies and across the life cycle. Since ovulation and thus progesterone’s presence is subclinical in normal-length cycles, we urgently need a convenient, home, once/cycle, inexpensive test of normal ovulation. Major funding is needed for ovulation-testing cycle-by-cycle over months or years in large population-based cohorts of adolescent, premenopausal and perimenopausal women. These women need to be followed for fertility and their later-life experiences of osteoporotic fracture, myocardial infarction, breast and endometrial cancers. In addition, all research with menstruating women participants and female mammals needs cycle-phase specific testing. It is difficult to perceive, much less to change, a current paradigm. With this journal issue, however, we have begun the important tasks of transforming concepts about women’s health, and setting the research agenda to advance the innovative understanding that women's reproductive and overall health becomes optimal when premenopausal menstrual cycle estradiol and progesterone actions are balanced within this complex system.


Endometrial Immunity for Embryo Implantation and Pregnancy Establishment

Abstract: The uterus is an organ for raising the fetus, and its lumen is lined by the endometrium. The endometrium is an important site for the implantation and maturation of fertilized eggs. The endometrium undergoes repetitive proliferation, maturation (decidualization), and exfoliation changes every menstrual cycle. At the same time, the number and type of endometrial immunocompetent cells vary during the menstrual cycle. At the implantation stage, the immunocompetent cells occupy approximately half of the endometrial cells. Immunocompetent cells normally eliminate pathogenic microorganisms to protect the body; however, they also promote immune tolerance to accept the fetus during pregnancy. The immunocompetent cells in the uterus can perform both these functions. With the establishment of pregnancy, stimuli from the trophoblast (placenta) and fetus can also change the immune environment of the uterus, and pregnancy can be maintained only when the immune system is well adapted to the stimuli of some hormones and the fetus. Immunity for the establishment of pregnancy is not simple because multiple immunocompetent cells are involved in establishing and maintaining pregnancy. To understand the immune mechanisms associated with the establishment of pregnancy, we have to learn about each immune cell. This review, therefore, discusses the roles and distribution of the immunocompetent cells inside the uterus during menstruation and early pregnancy.

The Tohoku journal of experimental medicine


Effect of antidepressant medications on semen parameters and male fertility

Abstract: Antidepressant medications are commonly used in males of reproductive age for long-term treatment of depression, as well as other disorders. Although antidepressants are known to be associated with sexual side-effects, their effects on semen parameters and other markers of male fertility have been less thoroughly described. The majority of available studies have focused on selective serotonin reuptake inhibitors, which have been shown to negatively impact semen quality in in vitro, animal and human studies. Fluoxetine, in particular, has been the subject of multiple studies and has been associated with gonadotoxic effects, including decreased sperm concentration and motility, increased deoxyribonucleic acid fragmentation, and decreased reproductive organ weights. Studies of several other selective serotonin reuptake inhibitors have yielded similar results. Reassuringly, this effect does seem to be reversible. The data regarding serotonin-norepinephrine reuptake inhibitors, norepinephrine-dopamine reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors and atypical antidepressants are sparse, varied and conflicting. Given the widespread and often long-term use of antidepressant medications, there is a clear need for further data regarding their impact on semen quality and male fertility.

International journal of urology : official journal of the Japanese Urological Association


Family Formations in Fertility Treatment 2018

Human Fertilisation and Embryology Authority

Abstract:
# Family formations in fertility treatment 2018
UK IVF and DI statistics for heterosexual, female same-sex and single patients
Published: 22 September 2020
[**Download the underlying data set in .xlsx (144KB)**](https://www.hfea.gov.uk/media/3294/family-formations-2018-complete-underlying-data-tables.xlsx).
[**Download a PDF version of this report (976KB)**](https://www.hfea.gov.uk/media/3234/family-formations-in-fertility-treatment-2018.pdf "Family formations 2018").
## Table of contents
- [Main points](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2018/#mainpoints)
- [Section 1. In vitro fertilisation (IVF) increasingly used over donor insemination (DI) for single patients and patients in female same-sex relationships](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2018/#Section1)
- [Section 2. IVF birth rates increased most for patients in female same-sex relationship as average age declined](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2018/#Section2)
- [Section 3. DI birth rates lowest for single patients due to higher average age](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2018/#Section3)
- [Section 4. Egg freezing most used by single patients](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2018/#Section4)
- [Section 5. NHS-funded cycles were more common for patients in heterosexual relationships](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2018/#Section5)
- [Section 6. Patients in female same-sex relationships used cost-reducing egg share programme at the highest rate](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2018/#...


Assisted reproductive technology in Japan: A summary report for 2017 by the Ethics Committee of the Japan Society of Obstetrics and Gynecology

Abstract: Annual summary report on assisted reproductive technology (ART) cycles performed in Japan during 2017, published by the Ethics Committee of the Japan Society of Obstetrics and Gynecology (JSOG).


Abstract:
1. Med Princ Pract. 2020;29(6):558-564. doi: 10.1159/000509016. Epub 2020 May 29.

How to Reduce the Potential Harmful Effects of Light on Blastocyst Development
during IVF.

Bódis J(1)(2), Gödöny K(1)(2), Várnagy Á(1)(2), Kovács K(1)(2), Koppán M(1)(2),
Nagy B(3)(4), Erostyák J(5)(6), Herczeg R(6), Szekeres-Barthó J(2)(6), Gyenesei
A(6), Kovács GL(2)(6)(7).

Author information:
(1)Department of Obstetrics and Gynecology, University of Pécs, Pécs, Hungary.
(2)MTA-PTE Human Reproduction Scientific Research Group, Pécs, Hungary.
(3)Department of Obstetrics and Gynecology, University of Pécs, Pécs, Hungary,
bernadett.nagy@aok.pte.hu.
(4)MTA-PTE Human Reproduction Scientific Research Group, Pécs, Hungary,
bernadett.nagy@aok.pte.hu.
(5)Institute of Physics, University of Pécs, Pécs, Hungary.
(6)Szentágothai Research Center, Pécs, Hungary.
(7)Department of Laboratory Medicine, University of Pécs, Pécs, Hungary.

PURPOSE: Earlier findings revealed the damaging effect of visible light on
zygotes and gametes. The aim of our study is to eliminate or significantly
reduce the potentially harmful effects of light exposure during in vitro
fertilization (IVF) or intracytoplasmic sperm injection (ICSI) and to
investigate the effect of light protection on embryo development and
implantation.
MATERIALS AND METHODS: To protect sperm cells, oocytes, and embryos from the
potential harmful effects of light exposure during laboratory procedures, we
created a dark environment for the cells and applied red filters on laboratory
lamps and UV or infrared filters in the microscopes in order to eliminate white
light exposure of the cells throughout all work stages.
RESULTS: The fertilization rate was significantly (p = 0.011) higher in
light-protected ICSI cycles. Blastocyst development rates (blastocyst/embryo)
were significantly (p < 0.001) higher in light-protected embryos than in those
manipulated in conventional light conditions both in IVF (20.9% difference) and
ICSI (38.6% difference). Numbers of clinical pregnancies/transfers of ICSI
fertilized day 5 blastocysts were also significantly (p = 0.040) higher in
light-protected conditions.
CONCLUSIONS: These data show that light protection has a positive effect on
fertilization rate and increases the blastocyst development as well as the
number of clinical pregnancies/transfers. Implementation of this light
protection method in IVF centers may improve the success rate while maintaining
maximal embryo safety.

© 2020 The Author(s) Published by S. Karger AG, Basel.

DOI: 10.1159/000509016
PMCID: PMC7768157
PMID: 32474560 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare that they have no conflicts
of interest.

Medical principles and practice : international journal of the Kuwait University, Health Science Centre


Melatonin and Female Reproduction: An Expanding Universe

Abstract: For more than a half century the hormone melatonin has been associated with vertebrate reproduction, particularly in the context of seasonal breeding. This association is due in large measure to the fact that melatonin secretion from the pineal gland into the peripheral circulation is a nocturnal event whose duration is reflective of night length, which of course becomes progressively longer during winter months and correspondingly shorter during the summer months. The nocturnal plasma melatonin signal is conserved in essentially all vertebrates and is accessed not just for reproductive rhythms, but for seasonal cycles of metabolic activities, immune functions, and behavioral expression. A vast literature on melatonin and vertebrate biology has accrued over the past 60 years since melatonin's discovery, including the broad topic of animal reproduction, which is far beyond the scope of this human-focused review. Although modern humans in the industrialized world appear in general to have little remaining reproductive seasonality, the relationships between melatonin and human reproduction continue to attract widespread scientific attention. The purpose of this chapter is to draw attention to some newer developments in the field, especially those with relevance to human fertility and reproductive medicine. As the vast majority of studies have focused on the female reproductive system, a discussion of the potential impact of melatonin on human male fertility will be left for others.


The Menstrual Cycle and Risk of Breast Cancer: A Review

Abstract: Cyclic hormonal stimulation of the breast tissue plays a significant role in breast carcinogenesis. Current risk factor models do not include direct measures of cycle characteristics although the effects of possible surrogates of cycle activity such as age at menarche and menopause, parity, and nursing time have been investigated. Future risk models should also include menstrual cycle length, regularity, number of cycles before first full-term pregnancy, and life-time number of cycles. New risk factor models for pre- and postmenopausal breast cancer are proposed here. Furthermore, there is a need for more long-term, prospective studies investigating menstrual cycle characteristics as data currently available are primarily retrospective and collected at one time-point only.


Unexplained recurrent pregnancy loss and unexplained infertility: twins in disguise

Abstract: Endometrial BCL6 protein levels are significantly elevated in women with unexplained recurrent pregnancy loss and unexplained infertility compared with fertile controls, with 79% of subfertile women displaying elevated BCL6. Among those with abnormal BCL6 who underwent laparoscopy, most were found to have endometriosis, suggesting a continuum of progesterone resistance and inflammatory/endometriosis-related endometrial dysfunction.


Endometriosis

Endometriosis


Prospective of low dose naltrexone use in treatment of autoimmune pathology and endometriosis

O.V. Furman

National Pirogov Memorial Medical University, Vinnytsya

Phil C Boyle

NeoFertility Clinic, Suite 7, 1st Floor, Beacon Mall, Sandyford, Dublin 18, Ireland. Phil.Boyle@NeoFertility.ie.

Abstract: There are still many complex issues in the management of autoimmune pathologies in gynecology and reproductology, endometriosis in particular. Naltrexone, a competitive antagonist of opiate receptors in the central and peripheral nervous systems, reveals new qualities such as effects on autoimmune processes. Naltrexone in low doses of 1.7–5 mg (Low Dose Naltrexone, LDN) revealed the opposite effect on opiate receptors in the form of a rebound effect and, as a consequence, a strong increase in endogenous endorphins and enkephalins. Studies of elevated levels of these neurotransmitters have provided evidence of a multidisciplinary beneficial effect on the immune system of people with endorphin and enkephalin deficiency, an association between the endogenous opiate system and cells and tissue growth in general and healthy immune function was confirmed. The most explored effects of them are such as blocking the synthesis ofpro inflammatory cytokines IL-6, IL-12, tumor necrosis factor, the effect on neuroglia through toll-like receptors, the effect on the cycle cells growth, especially malignant tumor cells, through interaction with opiate growth factor, modulation synthesis of T- and B-lymphocytes. Growing evidence of LDN efficacy is becoming a potentially effective clinical practice in autoimmune pathologies, but still off-label used.Some data of clinical trials is presented. Four studies with Crohn's disease with results of relief of symptoms and remission, including experience in pediatrics. Three clinical trials with LDN results in multiple sclerosis with improved quality of life and improved symptoms. The scientific hypothesis suggests the success of LDN due to the reduction of induced nitric oxide synthase activity. The success of management of patients with malignant tumors is also presented. The article contains the latest data from clinical trials on reported serious and non-serious side effects of naltrexone at various doses, including data confirming the safety of taking mid-therapeutic naltrexone doses throughout pregnancy. These effects of LDN may prove to be effective in management patients with endometriosis.


Dmitry M. Kissin

Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, CDC

Abstract: Assisted Reproductive Technology Surveillance - United States, 2017. Sunderam S, Kissin DM, Zhang Y, Jewett A, Boulet SL, Warner L, Kroelinger CD, Barfield WD. PROBLEM/CONDITION: Since the first U.S. infant conceived with assisted reproductive technology (ART) was born in 1981, both the use of ART and the number of fertility clinics providing ART services have increased steadily in the United States. ART includes fertility treatments in which eggs or embryos are handled in the laboratory (i.e., in vitro fertilization [IVF] and related procedures). Although the majority of infants conceived through ART are singletons, women who undergo ART procedures are more likely than women who conceive naturally to have multiple-birth infants because multiple embryos may be transferred. Multiple births can pose substantial risks for both mothers and infants, including obstetric complications, preterm birth (<37 weeks), and low birthweight (<2,500 g). This report provides state-specific information for the United States (including the District of Columbia and Puerto Rico) on ART procedures performed in 2017 and compares birth outcomes that occurred in 2017 (resulting from ART procedures performed in 2016 and 2017) with outcomes for all infants born in the United States in 2017. PERIOD COVERED: 2017. DESCRIPTION OF SYSTEM: In 1995, CDC began collecting data on ART procedures performed in fertility clinics in the United States as mandated by the Fertility Clinic Success Rate and Certification Act of 1992 (Public Law 102-493 [October 24, 1992]). Data are collected through the National ART Surveillance System (NASS), a web-based data collection system developed by CDC. This report includes data from the 50 states, the District of Columbia, and Puerto Rico. RESULTS: In 2017, a total of 196,454 ART procedures (range: 162 in Alaska to 24,179 in California) with at least one embryo transferred were performed in 448 U.S. fertility clinics and reported to CDC. These procedures resulted in 68,908 live-birth deliveries (range: 67 in Puerto Rico to 8,852 in California) and 78,052 infants born (range: 85 in Puerto Rico to 9,926 in California). Nationally, the number of ART procedures performed per 1 million women of reproductive age (15-44 years) was 3,040. ART use rates exceeded the national rate in 14 states (Connecticut, Delaware, District of Columbia, Hawaii, Illinois, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, Utah, Vermont, and Virginia). ART use exceeded 1.5 times the national rate in seven states (Connecticut, the District of Columbia, Illinois, Maryland, Massachusetts, New Jersey, and New York). Nationally, among all ART transfer procedures, the average number of embryos transferred increased slightly with increasing age (1.3 among women aged <35 years, 1.4 among women aged 35-37 years, and 1.5 among women aged >37 years). This year, single-embryo transfer (SET) rates among all embryo-transfer procedures are presented instead of elective single-embryo transfer procedures previously reported. Nationally, SET rates were 67.3% (range: 38.9% in South Dakota to 90.4% in Delaware), 65.0% (range: 23.6% in Puerto Rico to 89.4% in Delaware), and 60.0% (range: 28.6% in Puerto Rico to 83.1% in Delaware) among women aged <35 years, aged 35-37 years, and aged >37 years, respectively. In 2017, ART contributed to 1.9% of all infants born in the United States (range: 0.4% in Puerto Rico to 5.0% in Massachusetts). Approximately 73.6% of ART-conceived infants were singleton infants. Overall, ART contributed to 14.7% of all multiple births, including 14.7% of all twin infants and 17.3% of all triplets and higher-order infants. ART-conceived twins accounted for approximately 96.5% (18,890 of 19,570) of all ART-conceived infants born in multiple deliveries. The percentage of multiple births was higher among infants conceived with ART (26.4%) than among all infants born in the total birth population (3.4%). Approximately 25.5% of ART-conceived infants were twins, and 0.9% were triplets and higher-order infants. Nationally, infants conceived with ART contributed to 4.5% of all low birthweight (<2,500 g) infants. Among ART-conceived infants, 20.2% had low birthweight, compared with 8.3% among all infants. ART-conceived infants contributed to 5.3% of all preterm (gestational age <37 weeks) infants. The percentage of preterm births was higher among infants conceived with ART (27.8%) than among all infants born in the total birth population (9.9%). The percentage of low birthweight among singletons was 8.1% among ART-conceived infants and 6.6% among all infants born. The percentage of preterm births among ART-conceived singleton infants was 14.0%, compared with 8.1% among all singleton infants. The percentages of small for gestational age infants was 7.6% among ART-conceived infants, compared with 9.9% among all infants. INTERPRETATION: Although singleton infants accounted for the majority of ART-conceived infants, multi

Morbidity and mortality weekly report. Surveillance summaries (Washington, D.C. : 2002)


Effectiveness of Cherries in Reducing Uric Acid and Gout: A Systematic Review

Ching-Wen Chien

Institute for Hospital Management, Tsing Hua University, Shenzhen Campus, China

Abstract:
Background: Previous studies have reported the use of complementary therapies to reduce the risk of gout attacks. In this study, we assessed the effectiveness of cherries in reducing uric acid levels associated with gout.

Methods: We searched for relevant studies on PubMed, Embase, and the Cochrane Library without restrictions on language from inception until August 15, 2019. The risk of bias was evaluated using the PRISMA statement and checklist, and the methodological quality was assessed using the Cochrane Collaboration tool.

Results: The six studies included in this systematic review reported decreases in the incidence and severity of gout following the ingestion of cherries. Gout patients regularly ingesting cherry extract/juice reported fewer gout flare ups than those patients who did not supplement their diets with cherry products. Overall, we observed a positive correlation between the consumption of tart cherry juice and a decrease in serum uric acid concentration.

Conclusions: Current evidence supports an association between cherry intake and a reduced risk of gout attacks. Note however that we were unable to conduct effective meta-analysis due to a lack of relevant studies and a high degree of variation in the methodologies and metrics used in previous studies. Further comprehensive trials or long-term follow-up studies will be required to evaluate the efficacy of cherry intake in treating patients with gout or hyperuricemia.

Evidence-based Complementary and Alternative Medicine : eCAM


Ovarian reserve markers in women using various hormonal contraceptives

Abstract:
Objectives: The aim of the study was to assess whether the ovarian reserve markers anti-Müllerian hormone (AMH) and antral follicle count (AFC) were lower among women using the progestin-only pill (POP) or levonorgestrel-releasing intrauterine system (LNG-IUS) and similar to the decrease observed in combined oral contraceptive (COC) pill users.

Methods: This retrospective study comprised 565 hormonal contraceptive users (COC, POP, LNG-IUS or contraceptive vaginal ring) and 983 non-hormonal contraceptive users, who were seen in two Danish fertility assessment and counselling clinics between 2015 and 2019. Adjusted multiple regression analysis was used to examine the differences in AMH and AFC between hormonal and non-hormonal contraceptive users.

Results: Compared with non-hormonal contraceptive users, AMH was 31.1% lower among COC users [95% confidence interval (CI) -39.6%, -25.9%; p < 0.001], 35.6% lower among POP users (95% CI -49.0%, -18.6%; p < 0.001) and 17.1% lower among LNG-IUS users (95% CI -31.4%, 0.002%; p = 0.052); no significant differences were seen among vaginal ring users. Compared with non-hormonal contraceptive users, AFC was 31.3% lower among COC users (95% CI -35.0%, -25.3%; p < 0.001) and 29.7% lower among POP users (-39.1%, -17.9%; p < 0.001); no significant differences were seen among LNG-IUS or vaginal ring users. Ovarian volume was more than 50% reduced among COC and vaginal ring users (p < 0.001) but was unchanged among POP and LNG-IUS users.

Conclusion: Assessment of ovarian reserve markers among users of all types of hormonal contraception should be interpreted cautiously and the type of contraceptive method considered.

The European Journal of Contraception & Reproductive Health Care : the Official  Journal of the European Society of Contraception


Theological and Anthropological Analysi of Procreation in the Context of Contemporary Debate on Naprotechnology

Abstract: Immersed in the world dominated by pragmatism, contemporary man seems to be thinking and functioning only according to the criteria of effective acting. However, life experience, philosophical reflection, and the truth of Revelation lead to the conclusion that the laws of nature must be respected in the name of care for man and for one’s genuine good, even though they may, in certain cases, limit the effectiveness of acting and the possibility to acquire current profit. This article justifies the necessity to respect natural law in the sphere of transmission of human life. The starting point of this scientific reflection is the theological vision of values and of the inviolability of human life on the basis of the description of creation from the Book of Genesis. The fundamental truths and moral norms are being neglected nowadays as—being so proud of modern technological achievements—man makes himself the creator and the master of human life. Although such activities seem impressive from the scientific point of view, they actually result in a number of serious contemporary and future threats. The second part of the article presents alarming aspects of artificial interventions in the sphere of life transmission. By exposing the threats and by trying to prevent them in the sphere of infertility treatment, the Church opposes the methods of artificial insemination and becomes engaged in promoting naprotechnology which is a method that expresses genuine humanism, and which gives hope not only to the parents who want to have a baby but also to the mankind that longs for propitious future.


Gut microbiome and CAR-T therapy

Gut microbiome and CAR-T therapy

Abstract: Considerable progress has been made in cancer therapeutics recently with targeted strategies that are efficacious and less toxic. Immunotherapy and chimeric antigen receptor (CAR) T-cells are increasingly being evaluated in a variety of tumors in the relapsed/refractory as well as frontline disease settings, predominantly in hematologic malignancies (HM). Despite impressive outcomes in select patients, there remains significant heterogeneity in clinical response to CAR T-cells. The gut microbiome has emerged as one of the key host factors that could potentially be modulated to enhance responses to immunotherapy. Several recent human studies receiving immunotherapy showed a significantly superior response and survival in patients with the more diverse gut microbiome. Currently, it is unknown if gut microbiota modulates anti-tumor responses to CAR T-cells. Based on molecular and immunological understanding, we hypothesize that strategically manipulating gut microbiota may enhance responses to CAR T-cells. In this review, we further discuss resistance mechanisms to CAR T-cells in HM, potential approaches to overcome resistance by harnessing gut microbiota and other related novel strategies.


The effect of oral contraceptive pills on the macula, the retinal nerve fiber layer, the ganglion cell layer and the choroidal thickness

Abstract:
BACKGROUN: To evaluate the effect of oral contraceptive pills (OCP) on the macula, the retinal nerve fiber layer (RNFL), the ganglion cell layer (GCL), and the choroidal thickness (CT).

METHODS: In this prospective observational cross-sectional study, 60 eyes of 30 healthy women taking monophasic OCP (0.03 mg ethinylestradiol and 0.15 mg levonorgestrel) for contraception for at least 1 year were compared with 60 eyes of a control group of 30 healthy women who were not taking any OCP. Spectral-Domain Optical Coherence Tomography (SD-OCT) was used to evaluate the macula, the RNFL, the GCL, and the CT. Measurements were taken in the follicular phase (day 3) of the last menstrual cycle in all women. The body mass index (BMI) scores of all participants were also recorded.

RESULTS: No disparity in terms of age and BMI between both groups was observed (p = 0.444, p = 0.074, respectively). All the macular parameters measurements were considerably lower in the OCP group compared to the control group (p < 0.001). Also, the RNFL thickness, the GCL thickness, and the CT were all significantly thinner in the OCP group (p < 0.001).

CONCLUSIONS: The use of OCP can cause significant changes in the retina and choroid thickness over 1 year period. The women who are using OCP for a longer duration could have some eye problems. OCT should be routinely done for follow up. Further long term studies are required, using different preparations of OCP. It is important to find out when this thickness alterations can be clinically significant or symptomatic and if these changes are reversible or not.


Association Between Fertility Treatment and Cancer Risk in Children

Susanne K Kjaer

Virus, Lifestyle and Genes, Danish Cancer Institute, Copenhagen, Denmark; Department of Gynaecology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. Electronic address: susanne@...

Abstract:
IMPORTANCE: An increasing number of children worldwide are born after the use of fertility treatment, although it remains unclear whether the treatment affects the risk of childhood cancer and whether any associations observed are due to the use of specific drugs, the use of specific procedures, or the underlying infertility.

OBJECTIVE: To examine the association between different types of fertility treatments and cancer risk in children.

DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study based on Danish population-based registry data and the Danish Infertility Cohort (individual record linkage) that included 1 085 172 children born in Denmark between January 1, 1996, and December 31, 2012, linked with parental information. There were a total of 2217 children diagnosed with cancer (follow-up occurred during 1996-2015).

EXPOSURES: Maternal fertility treatment during the index pregnancy, including the use of fertility drugs (clomiphene [n = 33 835], gonadotropins [n = 57 136], gonadotropin-releasing hormone analogs [n = 38 653], human chorionic gonadotropin [n = 68 181], progesterone [n = 41 628], and estrogen [n = 16 948]) and assisted reproductive technology (in vitro fertilization [n = 19 448], intracytoplasmic sperm injection [n = 13 417], and frozen embryo transfer [n = 3356]). Each exposure was examined separately and compared with children born to fertile women.

MAIN OUTCOMES AND MEASURES: Hazard ratios and incidence rate differences for childhood cancer.

RESULTS: After 12.2 million person-years of follow-up (mean, 11.3 years), the incidence rate of childhood cancer was 17.5 per 100 000 for children born to fertile women (n = 910 291) and 44.4 per 100 000 for children born after the use of frozen embryo transfer (n = 3356). Compared with children born to fertile women, the use of frozen embryo transfer was associated with an elevated risk of childhood cancer (14 cancer cases; hazard ratio, 2.43 [95% CI, 1.44 to 4.11]; incidence rate difference, 26.9 [95% CI, 2.8 to 51.0] per 100 000), mainly due to an increased risk of leukemia (5 cancer cases; incidence rate, 14.4 per 100 000; hazard ratio, 2.87 [95% CI, 1.19 to 6.93]; incidence rate difference, 10.1 [95% CI, -4.0 to 24.2] per 100 000) and sympathetic nervous system tumors (<5 cancer cases; hazard ratio, 7.82 [95% CI, 2.47 to 24.70]). There were no statistically significant associations with the use of the other types of fertility treatment examined.

CONCLUSIONS AND RELEVANCE: Among children born in Denmark, the use of frozen embryo transfer, compared with children born to fertile women, was associated with a small but statistically significant increased risk of childhood cancer; this association was not found for the use of other types of fertility treatment examined.


Nocturnal finger skin temperature in menstrual cycle tracking: ambulatory pilot  study using a wearable Oura ring

Abstract:
Background: Body temperature is a common method in menstrual cycle phase tracking because of its biphasic form. In ambulatory studies, different skin temperatures have proven to follow a similar pattern. The aim of this pilot study was to assess the applicability of nocturnal finger skin temperature based on a wearable Oura ring to monitor menstrual cycle and predict menstruations and ovulations in real life.

Methods: Volunteer women (n = 22) wore the Oura ring, measured ovulation through urine tests, and kept diaries on menstruations at an average of 114.7 days (SD 20.6), of which oral temperature was measured immediately after wake-up at an average of 1.9 cycles (SD 1.2). Skin and oral temperatures were compared by assessing daily values using repeated measures correlation and phase mean values and differences between phases using dependent t-test. Developed algorithms using skin temperature were tested to predict the start of menstruation and ovulation. The performance of algorithms was assessed with sensitivity and positive predictive values (true positive defined with different windows around the reported day).

Results: Nocturnal skin temperatures and oral temperatures differed between follicular and luteal phases with higher temperatures in the luteal phase, with a difference of 0.30 °C (SD 0.12) for skin and 0.23 °C (SD 0.09) for oral temperature (p < 0.001). Correlation between skin and oral temperatures was found using daily temperatures (r = 0.563, p < 0.001) and differences between phases (r = 0.589, p = 0.004). Menstruations were detected with a sensitivity of 71.9-86.5% in window lengths of ±2 to ±4 days. Ovulations were detected with the best-performing algorithm with a sensitivity of 83.3% in fertile window from - 3 to + 2 days around the verified ovulation. Positive predictive values had similar percentages to those of sensitivities. The mean offset for estimations were 0.4 days (SD 1.8) for menstruations and 0.6 days (SD 1.5) for ovulations with the best-performing algorithm.

Conclusions: Nocturnal skin temperature based on wearable ring showed potential for menstrual cycle monitoring in real life conditions.


Strong Evidences of the Ovarian Carcinoma Risk in Women after IVF Treatment: A Review Article

Abstract:
BACKGROUND: In-vitro fertilization (IVF) has been very popular since the birth of the first "test-tube" baby. This method is the last hope and the most serious solution for couples with infertility problems. Although childbearing is a concern of many couples, it must always be noted that any method can also have disadvantages. Thus, many studies have been done on the problems encountered by this method.

METHODS: We searched for relevant articles in Pub Med, Springer, Elsevier, and Google Scholar databases, and studied more than 70 papers. Keywords used included ovarian cancer, in vitro fertilization, gonadotropin hormone, clomiphene citrate, and infertility.

RESULTS: Due to the large number of studies, high doses of the ovulation-stimulating drugs and their repeated use in this method can increase the risk of the ovarian hyper stimulation syndrome (OHSS), and ovarian cysts, which can lead to ovarian cancer. Also, an increase in the risk of developing ovarian cancer can be due to the increased duration of treatment for up to 12 months and the high doses of medications that are followed by defecation and failure of this treatment.

CONCLUSION: Due to the increase in the rates of infertility treatments and the incidence of gynecological cancers, especially ovarian cancer, this method need to be used with caution. IVF clients and candidates should be informed about potential future risks. People should be evaluated genetically for their history of ovarian cancer and be more aware of the importance of "Personalized medicine".


Oral contraceptive and intrauterine device use and the risk of cervical intraepithelial neoplasia grade III or worse: a population-based study

Leon F A G Massuger

Department of Obstetrics and Gynaecology, Radboud university medical center, PO Box 9101, 6500HB, Nijmegen, the Netherlands. Electronic address: leon.massuger@radboudumc.nl.

Ruud L M Bekkers

Department of Obstetrics and Gynaecology, Catharina Hospital, PO Box 1350, 5602ZA, Eindhoven, the Netherlands. Electronic address: ruud.bekkers@radboudumc.nl.

Abstract:
Objective: Hormonal contraceptive use has been associated with the development of cervical cancer, although inconsistent results are reported on the association with intrauterine device (IUD) use. The aim of this study was to evaluate the association between the type of contraceptive use and the development of cervical intraepithelial neoplasia grade III or worse (CIN3+).

Methods: A retrospective population-based cohort study including women aged 29-44 years attending the cervical cancer screening program with normal cytology between 2005 and 2009 identified from the Dutch Pathology Registry. Subgroups with at least 5 years registered use of an oral contraceptive (OC) or IUD were compared with non-users. Risk ratios of CIN3+ were estimated per contraceptive type.

Result: s702,037 women were included with a median follow-up of 9.7 years, of which 6705 (0.96%) and 559 (0.08%) women developed CIN3 and cervical cancer, respectively. IUD use was associated with an increased risk of developing CIN3+ (risk ratio (RR) 1.51, 95% confidence interval (CI) 1.32-1.74), and OC use was associated with an increased risk of developing CIN3+ (RR 2.77, 95%CI 2.65-3.00) and cervical cancer (RR 2.06, 95%CI 1.52-2.79). The risk of developing CIN3+ and cervical cancer was higher for OC users compared with IUD users (RR 1.83, 95%CI 1.60-2.09 and RR 1.70, 95%CI 1.00-2.90, respectively).

Conclusions: Both OC use and IUD use were associated with an increased risk of developing CIN3+. However, for women with a contraceptive wish, an IUD seems safer than an OC as the risk of developing CIN3+ and cervical cancer was higher for OC users.


Fecundability in relation to use of fertility awareness indicators in a North American preconception cohort study

Elizabeth E Hatch

Department of Epidemiology Boston University School of Public Health Boston MA USA

Kenneth J Rothman

Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA

Lauren A Wise

Slone Epidemiology Center at Boston University, Boston, Massachusetts and 2Lombardi Comprehensive Cancer Center at Georgetown University Medical Center, Washington, District of Columbia

Abstract:
OBJECTIVE: To quantify the frequency of use of selected fertility awareness indicators and to assess their influence on fecundability.

DESIGN: Web-based prospective cohort study.

SETTING: Not applicable.

PATIENT(S): Female pregnancy planners, aged 21-45 years, attempting conception for ≤6 cycles at study entry.

INTERVENTION(S): None.

MAIN OUTCOME MEASURE(S): We ascertained time to pregnancy, in menstrual cycles, with bimonthly questionnaires. We estimated adjusted fecundability ratios (FRs) and confidence intervals (CIs) using proportional probabilities models, controlling for age, income, education, smoking, intercourse frequency, and other lifestyle and reproductive factors.

RESULT(S): A total of 5,688 women were analyzed, with a mean age of 29.9 years and mean time trying of 2.1 cycles at baseline; 30% had ever been pregnant. At baseline, 75% were using one or more fertility indicators (counting days or charting menstrual cycles [71%], measuring basal body temperature [BBT, 21%], monitoring cervical fluid [39%], using urine LH tests [32%], or feeling for changes in position of the cervix [12%]). Women using any fertility indicator at baseline had higher subsequent fecundability (adjusted FR 1.25, 95% CI 1.16-1.35) than those not using any fertility indicators. For each individual indicator, adjusted FRs ranged from 1.28-1.36, where 1.00 would indicate no relation with fecundability. The adjusted FR for women using a combination of charting days, cervical fluid, and urine LH was 1.48 (95% CI 1.31-1.67) relative to women using no fertility indicators.

CONCLUSION(S): In a North American preconception cohort study, use of fertility indicators indicating the fertile window was common, and was associated with greater fecundability.


NaProTechnology: Healthcare women really need

Renee Mirkes

Pontifical John Paul II Institute for Studies on Marriage and Family

Research and Reports in Gynecology and Obstetrics


Chronic Endometritis: Old Problem, Novel Insights and Future Challenges

Luis Alonso

Unidad de Endoscopia Ginecológica, Centro Gutenberg, Málaga, Spain.

Jvan Casarin

Department of Obstetrics and Gynecology, "Filippo Del Ponte" Hospital, University of Insubria, Varese, Italy.

Elena Puente

Assisted Reproduction Unit, Fertia Clinic, Fuengirola, Málaga, Spain.

Abstract: Chronic endometritis (CE) is a poorly investigated pathology which has been related to adverse reproductive outcomes, such as implantation failure and recurrent miscarriage. In this paper, we aim to provide an overview of diagnosis, etiology, pathophysiology and treatment of CE, its impact on endometrial microenvironment and its association with infertility. We present a narrative review of the current literatures, synthesizing the findings retrieved from searches of computerized databases. CE is more prevalent in infertile patients. Effective antibiotic treatment of CE seems to improve the pregnancy and live birth rate in patients with unexplained recurrent pregnancy loss (RPL), and increase ongoing pregnancy rate in patients with recurrent implantation failure. In order to increase the diagnostic accuracy, immunohistochemistry is recommended besides the conventional histology. In addition, hysteroscopy could be considered as gold standard tool for diagnosis, considering its high correlation with histological findings. CE, as the chronic inflammation of endometrium, is usually asymptomatic and probably underestimated. Interaction of bacteria with endometrial microenvironment promotes changes in leukocyte population, cytokine production and growth factors which support its negative impact on endometrial receptivity. Nevertheless, standardization of the criteria for histopathological diagnosis and immunohistochemistry technique needs to be defined.

International Journal of Fertility & Sterility


Early- and Late-Luteal-Phase Estrogen and Progesterone Levels of Women with Premenstrual Dysphoric Disorder

Abstract: : Objective/introduction: The dynamics of ovarian hormone fluctuations during the luteal phase of the menstruation cycle were previously suggested to contribute to the development of premenstrual dysphoric disorder (PMDD) symptoms, but adequate empirical evidence has not been obtained from hormone concentration studies. We prospectively evaluated estrogen and progesterone levels in the early luteal (EL) and late luteal (LL) phases in women with PMDD and the association of these levels with PMDD symptom severity. Methods: 63 women with PMDD and 53 controls without such severe symptoms were evaluated for the estrogen and progesterone levels, and PMDD severity in the EL and LL phases. Results: The results demonstrated that the women with PMDD had a lower EL-phase estrogen level than the controls. Covariant analysis demonstrated that the interaction term between EL-phase estrogen and EL-phase progesterone level was associated with PMDD severity. Among women with lower EL estrogen levels, higher EL-phase progesterone was observed among the women with PMDD versus controls. These results suggest that low EL-phase estrogen level could moderate the provoking effect of EL progesterone in women with PMDD. Overall, these data suggest a possible role of estrogen and progesterone in the development of PMDD symptoms.

International journal of environmental research and public health


A Case-Control Study of Breast Cancer in Northeast of Iran: The Golestan Cohort  Study

Abstract:
Background: The incidence and survival of breast cancer (BC) vary across countries. This study aimed to determine risk factors for BC and estimate the overall survival rate in BC patients of the Golestan Cohort Study (GCS).

Methods: This case-control study was performed among participants of the GCS. Cases (N = 99) consisted of women who were diagnosed with BC and controls (n = 400) were selected out of women participating in the same cohort and had not developed any cancer during the follow-up period. Controls were frequency matched to case on both place of residency and 5-year categories of age.

Results: Considering confounding variables, logistic regression analysis manifested a reverse association between parity and BC (OR [odds ratio] = 0.87, 95% CI: 0.80-0.95, P = 0.001). In addition, we found women who had family history of any cancer (OR = 1.63, 95% CI: 1.02-2.60, P = 0.04) and long term oral contraceptive (OCP) use (≥10 years) (OR = 3.17, 95% CI: 1.27-7.95, P = 0.01) were at higher risk of BC. Of the total patients, 23 (23.2%) were died due to BC after a mean follow-up of 102.4 ± 5.31 months. Using the Kaplan-Meier analysis, the 5-year survival in these patients was 74%.

Conclusion: In the Golestan Cohort population, long term OCP use and family history of cancer were risk factors for BC, while parity was a protective factor. The 5-year survival of BC patients in the GCS is still lower relative to Europe and the United States.


Preconception Perceived Stress Is Associated with Reproductive Hormone Levels and Longer Time to Pregnancy

Sunni L Mumford

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Abstract:
Background: Women who experience pregnancy loss are especially prone to high stress, though the effects of stress on reproductive outcomes in this vulnerable population are unknown. We assessed relationships between perceived stress and hormones, anovulation, and fecundability among women with prior loss.

Methods: One thousand two hundred fourteen women with 1-2 prior losses were followed for ≤6 cycles while attempting pregnancy and completed end-of-cycle stress assessments. For cycles 1 and 2, women also collected daily urine and completed daily perceived stress assessments. We assessed anovulation via. an algorithm based on human chorionic gonadotropin (hCG), pregnanediol-3-glucuronide (PdG), luteinizing hormone (LH), and fertility monitor readings. Pregnancy was determined via. hCG. Adjusted weighted linear mixed models estimated the effect of prospective phase-varying (menses, follicular, periovulatory, and luteal) perceived stress quartiles on estrone-1-glucuronide (E1G), PdG, and LH concentrations. Marginal structural models accounted for time-varying confounding by hormones and lifestyle factors affected by prior stress. Poisson and Cox regression estimated risk ratios and fecundability odds ratios of cycle-varying stress quartiles on anovulation and fecundability. Models were adjusted for age, race, body mass index (BMI), parity, and time-varying caffeine, alcohol, smoking, intercourse, and pelvic pain.

Results: Women in the highest versus lowest stress quartile had lower E1G and PdG concentrations, a marginally higher risk of anovulation [1.28; 95% confidence interval (CI) = 1.00, 1.63], and lower fecundability (0.71; 95% CI = 0.55, 0.90).

Conclusion: Preconception perceived stress appears to adversely affect sex steroid synthesis and time to pregnancy. Mechanisms likely include the effects of stress on ovulatory function, but additional mechanisms, potentially during implantation, may also exist.


Occult Uterine Malignancy at the Time of Surgery for Uterine Fibroids: A Systematic Review

Journal of Minimally Invasive Gynecology


State of the Fertility Sector 2018/2019

State of the Fertility Sector 2018/2019

Human Fertilisation and Embryology Authority


Pre-conception 25-hydroxyvitamin D (25(OH)D) and fecundability

D D Baird

Epidemiology Branch, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709, USA

A Z Steiner

University of North Carolina at Chapel Hill

Abstract:
STUDY QUESTION: Is pre-conception 25(OH)D associated with the per cycle probability of conception, i.e fecundability, in a prospective cohort study?

SUMMARY ANSWER: There are suggestive associations of high 25(OH)D (at least 50 ng/ml) with increased fecundability and low 25(OH)D (<20 ng/ml) with reduced fecundability, but the estimates were imprecise.

WHAT IS KNOWN ALREADY: Vitamin D has been associated with reproductive function and fertility in animal studies, but few human studies exist.

STUDY DESIGN, SIZE, DURATION: This community-based prospective cohort study included 522 women attempting to become pregnant between 2010 and 2016. The women completed online daily and monthly diaries until a positive home pregnancy test was observed or 12 months had elapsed.

PARTICIPANTS/MATERIALS, SETTING, METHODS: The study included women from central North Carolina who were aged 30-44 with no history of infertility, with no more than 3 months of attempt time at recruitment. Women recorded vaginal bleeding so that the ongoing number of attempt cycles could be counted and used to quantify a woman's pregnancy attempt time. Blood collected at the study entry was analysed for 25(OH)D using liquid chromatography tandem mass spectrometry. Associations with fecundability were estimated with a log-binomial discrete time-to-event model.

MAIN RESULTS AND THE ROLE OF CHANCE: Among 522 women, 257 conceived during the study. The mean age was 33 years and the mean 25(OH)D was 36 ng/ml. There was an estimated 10% higher fecundability with each 10 ng/ml increase in 25(OH)D (fecundability ratio (FR) 1.10, 95% CI: 0.96, 1.25). The suggestive dose-response association with the continuous measure of 25(OH)D was driven by women in the lowest and the highest categories of 25(OH)D. Compared to women with 25(OH)D of 30-40 ng/ml, women below 20 ng/ml had an estimated 45% reduction in fecundability (FR (CI): 0.55 (0.23, 1.32)), and women with at least 50 ng/ml had an estimated 35% increase in fecundability (FR (CI): 1.35 (0.95, 1.91)). Across these three categories (25(OH)D of <20 ng/ml, 30-40 ng/ml and > 50 ng/ml), the probability of taking longer than 6 months to conceive was, respectively, 51% (17%, 74%), 28% (17%, 39%) and 15% (10%, 37%).

LIMITATIONS, REASONS FOR CAUTION: While the distribution of 25(OH)D was wide, the number of observed cycles with high 25(OH)D (N = 107) or low 25(OH)D (N = 56) was small.

WIDER IMPLICATIONS OF THE FINDINGS: Our findings are consistent with prior reports of reduced fertility in women with 25(OH)D concentrations below the clinically defined deficiency level (20 ng/ml). Further studies are needed to evaluate the possible reproductive benefits of considerably higher 25(OH)D concentration (>50 ng/ml).

STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (NIH) under award numbers R00HD079659 and R01HD067683 and supported in part by the Intramural Research Program of the National Institute of Environmental Health Sciences, under projects ES103086, ES049003 and ES044003. ClearBlue ovulation predictor kits were generously donated to AMZJ and AJW by Swiss Precision Diagnostics. Drs Wilcox and Jukic report non-financial support from Swiss Precision Diagnostics during the conduct of the study; Dr Jukic reports non-financial support from Theralogix, LLC, outside the submitted work. Otherwise there are no competing interests.

TRIAL REGISTRATION NUMBER: N/A.


The Preconception Period analysis of Risks and Exposures Influencing health and Development (PrePARED) consortium

Harville EW, Mishra GD, Yeung E, Mumford SL, Schisterman EF, Jukic AM, Hatch EE, Mikkelsen EM, Jiang H, Ehrenthal DB, Porucznik CA, Wen SW, Harvey A, Symons Downs D, Yajnik C, Santillan D, Santillan M, McElrath TF, Woo JG, Urbina EM, Chavarro JE, Sotres-Alvarez D, Bazzano L, Zhang J, Steiner A, Gunderson EP, Wise LA, Stanford JB

Abstract:
BACKGROUND: Preconception health may have intergenerational influences. We have formed the PrePARED (Preconception Period Analysis of Risks and Exposures influencing health and Development) research consortium to address methodological, conceptual, and generalisability gaps in the literature.

OBJECTIVES: The consortium will investigate the effects of preconception exposures on four sets of

outcomes: (1) fertility and miscarriage; (2) pregnancy-related conditions; (3) perinatal and child health; and (4) adult health outcomes.

POPULATION: A study is eligible if it has data measured for at least one preconception time point, has a minimum of selected core data, and is open to collaboration and data harmonisation.

DESIGN: The included studies are a mix of studies following women or couples intending to conceive, general-health cohorts that cover the reproductive years, and pregnancy/child cohort studies that have been linked with preconception data. The majority of the participating studies are prospective cohorts, but a few are clinical trials or record linkages.

METHODS: Data analysis will begin with harmonisation of data collected across cohorts. Initial areas of interest include nutrition and obesity; tobacco, marijuana, and other substance use; and cardiovascular risk factors.

PRELIMINARY

RESULTS: Twenty-three cohorts with data on almost 200 000 women have combined to form this consortium, begun in 2018. Twelve studies are of women or couples actively planning pregnancy, and six are general-population cohorts that cover the reproductive years; the remainder have some other design. The primary focus for four was cardiovascular health, eight was fertility, one was environmental exposures, three was child health, and the remainder general women's health. Among other cohorts assessed for inclusion, the most common reason for ineligibility was lack of prospectively collected preconception data.

CONCLUSIONS: The consortium will serve as a resource for research in many subject areas related to preconception health, with implications for science, practice, and policy.


Stratification of fertility potential according to cervical mucus symptoms:  achieving pregnancy in fertile and infertile couples

Marian Corkill

Ovulation Method Research and Reference Centre of Australia, Melbourne, Australia

Abstract: Women wishing to conceive are largely unaware of fertility symptoms at the time of ovulation. This study investigated the effectiveness of fertility-awareness in achieving pregnancy, particularly fertile mucus pattern, in the context of infertility. The 384 eligible participants were taken from consecutive women desiring pregnancy who attended 17 Australian Billings Ovulation Method(®) clinics from 1999-2003. This cohort included couples with infertility ≥12 months (51%) and female age >35 years (28%). Under fertility-awareness instruction, pregnancy was achieved by 240 couples (62.5%) after maximum follow-up of two years. Mucus symptom observations effectively stratified 'low pregnancy-potential' (35.2%) and 'high pregnancy-potential' groups. Pregnancy rates were ∼30% higher in the latter group (44.4% versus 72.3%) in addition to consistent effects observed on pregnancy achievements within subgroups defined by prognostic factors such as duration of infertility (p = 0.001) and increasing female age (p = 0.04). Fertile symptoms were also associated with significantly shorter time to conception (4.2 versus 6.4 months) in a survival analysis (p = 0.003). Billings Ovulation Method(®) observations strongly predicted successful conception. This has the capacity to provide a rapid, reliable and cost-effective approach to stratifying fertility potential, including directing timely and targeted investigations/management, and is accessible for women who may be remote from primary or specialist care.


Lowered Plasma Steady-State Levels of Progesterone Combined With Declining Progesterone Levels During the Luteal Phase Predict Peri-Menstrual Syndrome and Its Major Subdomains

Abstract:
Background: It is unknown whether lowered steady state levels of sex hormones coupled with changes in those hormones during the menstrual cycle are associated with premenstrual syndrome (PMS).

Objective: To examine associations between levels of progesterone and oestradiol during the menstrual cycle and PMS considering different diagnostic criteria for PMS.

Methods: Forty-one women aged 18-45 years with a regular menstrual cycle completed the Daily Record of Severity of Problems (DRSP) for all 28 consecutive days of the menstrual cycle. Blood was sampled at days 7, 14, 21, and 28 to assay oestradiol and progesterone.

Results: We developed a new diagnosis of peri-menstrual syndrome, which is characterized by increased DRSP severity in pre and post-menstrual periods and increased scores on the major DRSP dimensions, i.e., depression, physio-somatic symptoms, breast tenderness and appetite, and anxiety. This new diagnosis performed better than classical diagnoses of PMS, including that of the American College of Obstetricians and Gynecologists (ACOG). Lowered steady state levels of progesterone, when averaged over the menstrual cycle, together with declining progesterone levels during the luteal phase predict severity of peri-menstrual symptoms. Steady state levels of oestradiol and declining oestradiol levels during the cycle are also related to DRSP severity although most of these effects appeared to be mediated by progesterone.

Conclusion: A significant increase in menstrual-cycle related symptoms can best be conceptualized as "peri-menstrual syndrome" and may result from insufficient progesterone production (relative corpus luteum insufficiency), which, in part may result from lowered oestradiol production indicating suboptimal pre-ovulatory follicular development.


Vertebral Fractures in Individuals With Type 2 Diabetes: More Than Skeletal  Complications Alone

Fjorda Koromani, Ling Oei, Enisa Shevroja, Katerina Trajanoska, Josje Schoufour, Taulant Muka, Oscar H Franco, M Arfan Ikram, M Carola Zillikens, Andr\ue G Uitterlinden, Gabriel P Krestin, Tassos Anastassiades, Robert Josse, Stephanie M Kaiser, David Goltzman, Brian C Lentle, Jerilynn C Prior, William D Leslie, Eugene McCloskey, Olivier Lamy, Didier Hans, Edwin H Oei, Fernando Rivadeneira

Abstract:
Objective: We aimed to assess whether individuals with type 2 diabetes (T2D) have increased risk of vertebral fractures (VFs) and to estimate nonvertebral fracture and mortality risk among individuals with both prevalent T2D and VFs. RESEARCH DESIGN AND

Methods: A systematic PubMed search was performed to identify studies that investigated the relationship between T2D and VFs. Cohorts providing individual participant data (IPD) were also included. Estimates from published summary data and IPD cohorts were pooled in a random-effects meta-analysis. Multivariate Cox regression models were used to estimate nonvertebral fracture and mortality risk among individuals with T2D and VFs.

Results: Across 15 studies comprising 852,705 men and women, individuals with T2D had lower risk of prevalent (odds ratio [OR] 0.84 [95% CI 0.74-0.95]; I (2) = 0.0%; P (het) = 0.54) but increased risk of incident VFs (OR 1.35 [95% CI 1.27-1.44]; I (2) = 0.6%; P (het) = 0.43). In the IPD cohorts (N = 19,820), risk of nonvertebral fractures was higher in those with both T2D and VFs compared with those without T2D or VFs (hazard ratio [HR] 2.42 [95% CI 1.86-3.15]) or with VFs (HR 1.73 [95% CI 1.32-2.27]) or T2D (HR 1.94 [95% CI 1.46-2.59]) alone. Individuals with both T2D and VFs had increased mortality compared with individuals without T2D and VFs (HR 2.11 [95% CI 1.72-2.59]) or with VFs alone (HR 1.84 [95% CI 1.49-2.28]) and borderline increased compared with individuals with T2D alone (HR 1.23 [95% CI 0.99-1.52]).

Conclusions: Based on our findings, individuals with T2D should be systematically assessed for presence of VFs, and, as in individuals without T2D, their presence constitutes an indication to start osteoporosis treatment for the prevention of future fractures.


322. Prolonged Amenorrhea Is Associated with Decreased Hip Bone Mineral Density in Women Living with HIV

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Hélène C F Côté

Women's Health Research Institute, H214-4500 Oak St, Vancouver, British Columbia V6H 3N1, Canada; Department of Pathology & Laboratory Medicine, University of British Columbia, Rm. G227 - 2211 Wesb...

Melanie C M Murray

Oak Tree Clinic, BC Women's Hospital and Health Centre, 4500 Oak St, Vancouver, British Columbia V5Z 0A7, Canada; Women's Health Research Institute, H214-4500 Oak St, Vancouver, British Columbia V6...

Abstract: Background Women living with HIV (WLWH) have higher rates of long-term amenorrhea (no flow for ≥12 months) than HIV-negative women. However, little is known about the consequences of amenorrhea for WLWH. Both amenorrhea and HIV are associated with lower areal bone mineral density (BMD); though the combined effect of both on BMD remains unclear. In this cross-sectional study we investigated whether prolonged amenorrhea adversely affects BMD among WLWH. Methods We investigated BMD (using a Hologic bone densitometer) and prolonged amenorrhea among WLWH and HIV-negative control women of similar socioeconomic backgrounds aged 19–68 in the CARMA cohort. Participants were stratified by HIV status and history of prolonged secondary amenorrhea defined as a self-reported absence of menses for at least one year in the past or present, occurring at age <45 years and not due to surgery, breastfeeding, pregnancy or hormonal contraception. Hip and spine Z-scores (ageand racestandardized BMD values) were compared between groups using linear models, followed by multivariable analysis of BMD-related factors. Results WLWH (N = 129) had significantly lower hip (mean±SD −0.4 ± 0.9 vs. 0.3 ± 1.1; P < 0.001) and spine (−0.5 ± 1.3 vs. 0.2 ± 1.3; P = 0.001) Z-scores vs. controls (N = 129). Multivariable linear regression found prolonged amenorrhea was independently related to lower hip (P = 0.01), but not spine (P = 0.94) BMD. Within WLWH, the effect of amenorrhea was also additive to that of HIV, with hip Z-scores of -0.8±0.9for those with amenorrhea vs. -0.3±0.8for those normally cycling (P = 0.01). Amongst WLWH, those with prolonged amenorrhea had higher rates of illicit substance use, smoking, chronic opioid therapy, hepatitis C viral infection, and poorer HIV viral control than those with normal menstruation. Conclusion These data suggest that WLWH having prolonged amenorrhea of ≥1 year’s duration are at increased risk for hip bone loss, a finding influenced by comorbid, HIV-associated conditions. Screening WLWH for menstrual history will allow early discovery of osteoporosis risk, and stimulate preventative measures to mitigate bone loss. Disclosures All authors: No reported disclosures.


Reprint of: Dating the Endometrial Biopsy


Myo-Inositol for the Prevention of Gestational Diabetes Mellitus. A Brief Review

Rosario D'Anna

Department of Obstetrics and Gynecology, University of Messina, Italy.

Abstract: Gestational Diabetes Mellitus (GDM) is one of the most frequent complications of pregnancy and is characterized by a carbohydrate intolerance which is diagnosed with the oral glucose tolerance test. The prevalence of GDM in our population is about 12%, but risk factors like a previous GDM, ethnicity, a parent with diabetes mellitus type 2 and maternal overweight may increase its occurrence. Complications of GDM are a pre-term birth (before 37 wk gestation), macrosomia (birth weight ≥4 kg) and gestational hypertension. Actually, GDM is principally treated with diet and, if it is necessary, with insulin; but the challenge is the prevention of GDM. Among the measures used, changes in life-style (diet+exercise) failed to prevent GDM whereas metformin showed conflicting results. A promising supplement is myo-inositol (MI) which was given from first trimester until delivery to women at risk for GDM reporting a significant decrease in GDM occurrence by more than 60% comparing to the placebo group. Recently, a secondary analysis from 3 randomized controlled trials demonstrated that MI may also significantly reduce some of GDM complications such as pre-term birth and macrosomia with a favorable impact on mother and fetus well being.

Journal of Nutritional Science and Vitaminology


Vaginal microbiome transplantation in women with intractable bacterial vaginosis

Debra Goldman-Wohl

Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Abstract: We report the results of a first exploratory study testing the use of vaginal microbiome transplantation (VMT) from healthy donors as a therapeutic alternative for patients suffering from symptomatic, intractable and recurrent bacterial vaginosis (ClinicalTrials.gov NCT02236429 ). In our case series, five patients were treated, and in four of them VMT was associated with full long-term remission until the end of follow-up at 5-21 months after VMT, defined as marked improvement of symptoms, Amsel criteria, microscopic vaginal fluid appearance and reconstitution of a Lactobacillus-dominated vaginal microbiome. One patient presented with incomplete remission in clinical and laboratory features. No adverse effects were observed in any of the five women. Notably, remission in three patients necessitated repeated VMT, including a donor change in one patient, to elicit a long-standing clinical response. The therapeutic efficacy of VMT in women with intractable and recurrent bacterial vaginosis should be further determined in randomized, placebo-controlled clinical trials.


Association of Use of Oral Contraceptives With Depressive Symptoms Among  Adolescents and Young Women

Erik J Giltay

Department of Psychiatry, Leiden University Medical Center, Leiden, the Netherlands

Albertine J Oldehinkel

Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands

Abstract:
Importance: Oral contraceptives have been associated with an increased risk of subsequent clinical depression in adolescents. However, the association of oral contraceptive use with concurrent depressive symptoms remains unclear.

Objectives: To investigate the association between oral contraceptive use and depressive symptoms and to examine whether this association is affected by age and which specific symptoms are associated with oral contraceptive use. DESIGN, SETTING, AND

Participants: Data from the third to sixth wave of the prospective cohort study Tracking Adolescents' Individual Lives Survey (TRAILS), conducted from September 1, 2005, to December 31, 2016, among females aged 16 to 25 years who had filled out at least 1 and up to 4 assessments of oral contraceptive use, were used. Data analysis was performed from March 1, 2017, to May 31, 2019.

Exposure: Oral contraceptive use at 16, 19, 22, and 25 years of age.

MAIN OUTCOMES AND MEASURES: Depressive symptoms were assessed by the DSM-IV-oriented affective problems scale of the Youth (aged 16 years) and Adult Self-Report (aged 19, 22, and 25 years).

Results: Data from a total of 1010 girls (743-903 girls, depending on the wave) were analyzed (mean [SD] age at the first assessment of oral contraceptive use, 16.3 [0.7]; (mean [SD] age at the final assessment of oral contraceptive use, 25.6 [0.6] years). Oral contraceptive users particularly differed from nonusers at age 16 years, with nonusers having a higher mean (SD) socioeconomic status (0.17 [0.78] vs -0.15 [0.71]) and more often being virgins (424 of 533 [79.5%] vs 74 of 303 [24.4%]). Although all users combined (mean [SD] ages, 16.3 [0.7] to 25.6 [0.6] years) did not show higher depressive symptom scores compared with nonusers, adolescent users (mean [SD] age, 16.5 [0.7] years) reported higher depressive symptom scores compared with their nonusing counterparts (mean [SD] age, 16.1 [0.6] years) (mean [SD] score, 0.40 [0.30] vs 0.33 [0.30]), which persisted after adjustment for age, socioeconomic status and ethnicity (β coefficient for interaction with age, -0.021; 95% CI, -0.038 to -0.005; P = .0096). Adolescent contraceptive users particularly reported more crying (odds ratio, 1.89; 95% CI, 1.38-2.58; P < .001), hypersomnia (odds ratio, 1.68; 95% CI, 1.14-2.48; P = .006), and more eating problems (odds ratio, 1.54; 95% CI, 1.13-2.10; P = .009) than nonusers.

Conclusions and Relevance: Although oral contraceptive use showed no association with depressive symptoms when all age groups were combined, 16-year-old girls reported higher depressive symptom scores when using oral contraceptives. Monitoring depressive symptoms in adolescents who are using oral contraceptives is important, as the use of oral contraceptives may affect their quality of life and put them at risk for nonadherence.


Cannabis and Male Fertility: A Systematic Review

Abstract:
PURPOSE: With cannabis consumption on the rise and use prominent among males of reproductive age it is essential to understand the potential impact of cannabis on male fertility. We reviewed the literature regarding the effects of cannabis on male fertility.

MATERIALS AND METHODS: We performed a literature search using PubMed®/MEDLINE® to identify relevant studies of the effects of cannabis on male fertility. Relevant studies were identified and reviewed.

RESULTS: The strongest evidence of cannabis induced alterations in male fertility is in the category of semen parameters. Research supports a role for cannabis in reducing sperm count and concentration, inducing abnormalities in sperm morphology, reducing sperm motility and viability, and inhibiting capacitation and fertilizing capacity. Animal models demonstrate a role for cannabis in testicular atrophy, and reduced libido and sexual function but to our knowledge these results have not yet been replicated in human studies. Studies of hormonal changes suggest inconclusive effects on testosterone levels, lowered luteinizing hormone levels and unchanged follicle-stimulating hormone levels.

CONCLUSIONS: Current research suggests that cannabis may negatively impact male fertility. Further studies are needed to validate that robust findings in animal models will carry over into human experience. Clinicians should be aware of these potential effects when prescribing medical marijuana therapies to men of reproductive age, and they should consider the degree of cannabis use as a possible component of a complete male infertility workup.


Levothyroxine to increase live births in euthyroid women with thyroid antibodies trying to conceive: the TABLET RCT

Dhillon-Smith RK, Middleton LJ, Sunner KK, Cheed V, Baker K, Farrell-Carver S, Bender-Atik R, Agrawal R, Bhatia K, Edi-Osagie E, Ghobara T, Gupta P, Jurkovic D, Khalaf Y, MacLean M, McCabe C, Mulbagal K, Nunes N, Overton C, Quenby S, Rai R, Raine-Fenning N, Robinson L, Ross J, Sizer A, Small R, Tan A, Underwood M, Kilby MD, Boelaert K, Daniels J, Thangaratinam S, Chan SY, Coomarasamy A

Abstract: Thyroid autoantibodies, specifically thyroid peroxidase antibodies, have been associated with miscarriage and pre-term birth in women with a normal thyroid function. Small randomised controlled trials have found that treatment with levothyroxine may reduce such adverse outcomes in pregnancy. The Thyroid AntiBodies and LEvoThyroxine (TABLET) trial was conducted to explore the effects of levothyroxine in euthyroid women with thyroid peroxidase antibodies. This was a randomised, double-blind, placebo-controlled, multicentre study conducted in 49 hospitals across the UK between 2011 and 2016. Euthyroid women who tested positive for thyroid peroxidase antibodies, were aged between 16 and 41 years and were trying to conceive either naturally or through assisted conception were eligible. Participants were randomised to levothyroxine at a dose of 50 mcg daily or placebo. The primary outcome was live birth at >= 34 completed weeks of gestation. Of the 19,556 women screened, 1420 were eligible and 952 were randomised. The live birth rate was 37% in the levothyroxine group and 38% in the placebo group (relative risk 0.97, 95% CI 0.83 to 1.14; p = 0.74). Levothyroxine therapy in a dose of 50 mcg per day does not improve live birth rate in euthyroid women with thyroid peroxidase antibodies.


Risk of prostate cancer for men fathering through assisted reproduction: nationwide population based register study

Abstract:
OBJECTIVE: To compare the risk and severity of prostate cancer between men achieving fatherhood by assisted reproduction and men conceiving naturally.

DESIGN: National register based cohort study.

SETTING: Sweden from January 1994 to December 2014.

PARTICIPANTS: 1 181 490 children born alive in Sweden during 1994-2014 to the same number of fathers. Fathers were grouped according to fertility status by mode of conception: 20 618 by in vitro fertilisation (IVF), 14 882 by intra-cytoplasmic sperm injection (ICSI), and 1 145 990 by natural conception.

MAIN OUTCOME MEASURES: Prostate cancer diagnosis, age of onset, and androgen deprivation therapy (serving as proxy for advanced or metastatic malignancy).

RESULTS: Among men achieving fatherhood by IVF, by ICSI, and by non-assisted means, 77 (0.37%), 63 (0.42%), and 3244 (0.28%), respectively, were diagnosed as having prostate cancer. Mean age at onset was 55.9, 55.1, and 57.1 years, respectively. Men who became fathers through assisted reproduction had a statistically significantly increased risk of prostate cancer compared with men who conceived naturally (hazard ratio 1.64, 95% confidence interval 1.25 to 2.15, for ICSI; 1.33, 1.06 to 1.66, for IVF). They also had an increased risk of early onset disease (that is, diagnosis before age 55 years) (hazard ratio 1.86, 1.25 to 2.77, for ICSI; 1.51, 1.09 to 2.08, for IVF). Fathers who conceived through ICSI and developed prostate cancer received androgen deprivation therapy to at least the same extent as the reference group (odds ratio 1.91; P=0.07).

CONCLUSIONS: Men who achieved fatherhood through assisted reproduction techniques, particularly through ICSI, are at increased risk for early onset prostate cancer and thus constitute a risk group in which testing and careful long term follow-up for prostate cancer may be beneficial.


Daily perceived stress and time to pregnancy: A prospective cohort study of women trying to conceive

Abstract:
BACKGROUND: Prior studies among women with impaired fecundity have consistently demonstrated a positive association between daily perceived stress and the ability to conceive. However, the effects of daily stress on time to pregnancy (TTP) among women with proven fertility is not known.

MATERIALS AND METHODS: One hundred and forty-three women ages 18-35, in a relationship of proven fertility, who desired to conceive were included in the analysis. Daily diaries recording perceived stress (scale 0-10) were completed for up to 7 menstrual cycles or until pregnancy. Cox proportional hazards regression models were used to estimate the association between time-varying perceived stress tertiles (high [>4.1-7.2], moderate [>2.7-4.1], and low [0.1-2.7]) and adjusted fecundability odds ratio (aFOR), 95% confidence intervals (CI), after taking into account age, parity, education, time-varying caffeine and alcohol intake, fertility awareness tracking, and cycle intent to conceive.

RESULTS: Among the 111 participants who completed daily diaries, 90 (81.1%) conceived. Women reporting high or moderate stress, versus low stress, had no difference in probability of achieving pregnancy (aFOR: 1.11 [95% CI: 0.58, 2.14]; and aFOR: 1.37 [0.71, 2.67]), respectively. Additional adjustment for intercourse frequency during narrow fertile window, or narrowing exposure focus to pre-ovulatory or pre-implantation stress did not appreciably alter the estimates.

CONCLUSION: Daily perceived stress was not adversely associated with TTP among women with proven fertility. While a growing body of evidence supports adverse effects of more severe stressful life events on female reproductive function, moderate psychological stress, commonly referred to as eustress, among relatively healthy women with proven fertility does not appear to adversely impact TTP.


Impact of aging on obstetric outcomes: defining advanced maternal age in Barcelona

Abstract:
BACKGROUND: Women of advanced maternal age (AMA) are a growing population, with higher obstetric risks. The Mediterranean population has specific characteristics different from other areas. Thus, the objective of this study was to establish a cut-off to define AMA in a selected mediterranean population coming from a tertiary referral private/mutual health hospital in Barcelona.

METHODS: Retrospective cohort of euploid singleton pregnancies delivered from January 2007 to June 2017. Main maternal outcomes were: gestational diabetes, preeclampsia, placenta previa, c-section and prolonged hospitalization (≥ 7 days). Main adverse perinatal outcomes were: stillbirth, prematurity, preterm prelabor rupture of membranes, low birth weight, need of admission at a neonatal intensive care unit and perinatal mortality. Adjustment for confounding factors (smoking, previous comorbilities, parity, assisted reproductive techniques (ART) and obesity) was performed.

RESULTS: A total of 25054 pregnancies were included. Mean maternal age was 34.7 ± 4.2 years, with 2807 patients in the group of age between 40 and 44 years (11.2%) and 280 patients ≥45 years (1.1%). Women at AMA had higher incidence of previous comorbilities (compared to the reference group of women < 30 years): prior c-section, chronic hypertension and obesity. In addition, they were more likely to use ART. After adjusting for confounding factors, maternal age was an independent and statistically significant risk factor for gestational diabetes (OR 1.66/2.80/3.14) for ages 30-39, 40-44 and ≥ 45 years respectively, c-section (OR 1.28/2.41/7.27) and placenta previa (OR 2.56/4.83) for ages 40-44 and ≥ 45 years respectively, but not for preeclampsia (neither early-onset nor late-onset). Risk of emergency c-section was only increased in women ≥45 years (OR, 2.03 (95% CI, 1.50-2.74). In the other groups of age, the increase in c-section rate was because of elective indications. Age ≥ 45 years was associated with iatrogenic prematurity < 37 weeks (OR 2.62, 95% CI 1.30-5.27). No other relevant associations between AMA and maternal or neonatal outcomes were found.

CONCLUSIONS: Maternal age is an independent risk factor for adverse obstetric outcomes. Age ≥ 40 years was associated to relevant increased risks and reveals to be an adequate cut-off to define AMA in our population.


Nutraceutical Supplements in the Thyroid Setting: Health Benefits beyond Basic Nutrition

Ulla Feldt-Rasmussen

Medical Endocrinology and Metabolism PE 2132, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark

Abstract: In recent years, there has been a growing interest in nutraceuticals, which may be considered as an efficient, preventive, and therapeutic tool in facing different pathological conditions, including thyroid diseases. Although iodine remains the major nutrient required for the functioning of the thyroid gland, other dietary components play important roles in clinical thyroidology-these include selenium, l-carnitine, myo-inositol, melatonin, and resveratrol-some of which have antioxidant properties. The main concern regarding the appropriate and effective use of nutraceuticals in prevention and treatment is due to the lack of clinical data supporting their efficacy. Another limitation is the discrepancy between the concentration claimed by the label and the real concentration. This paper provides a detailed critical review on the health benefits, beyond basic nutrition, of some popular nutraceutical supplements, with a special focus on their effects on thyroid pathophysiology and aims to distinguish between the truths and myths surrounding the clinical use of such nutraceuticals.


A brief update on the evidence supporting the treatment of infertility in  polycystic ovary syndrome

Costello MF, Misso ML, Balen A, Boyle J, Devoto L, Garad RM, Hart R, Johnson L, Jordan C, Legro RS, Norman RJ, Moran L, Mocanu E, Qiao J, Rodgers RJ, Rombauts L, Tassone EC, Thangaratinam S, Vanky E, Teede HJ

Abstract:
Background: Polycystic ovary syndrome (PCOS) is complex with reproductive, metabolic and psychological features. Infertility is a prevalent presenting feature of PCOS with approximately 75% of these women suffering infertility due to anovulation, making PCOS by far the most common cause of anovulatory infertility. Previous guidelines either lacked rigorous evidence-based processes, did not engage consumer and international multidisciplinary perspectives, or were outdated.

Aims: This review paper aims to provide a brief update on the best available and most current research evidence supporting the treatment of PCOS which informed the recommendations in the assessment and treatment of infertility section of the international evidence-based guideline on PCOS 2018.

MATERIALS AND Methods: International evidence-based guideline development engaged professional societies and consumer organisations with multidisciplinary experts and women with PCOS directly involved at all stages.

Results: Lifestyle change alone is considered the first-line treatment for the management of infertile anovulatory PCOS women who are overweight or obese. Letrozole should now be considered first-line pharmacological treatment for ovulation induction to improve fertility outcomes. Clomiphene citrate alone and metformin alone could also be used as first-line pharmacological therapy, although both are less effective than letrozole and metformin is less effective than clomiphene citrate in obese women. Gonadotrophins or laparoscopic ovarian surgery are usually second-line ovulation induction therapies. In the absence of an absolute indication for in vitro fertilisation (IVF) / intracytoplasmic sperm injection, women with PCOS and anovulatory infertility could be offered IVF as third-line therapy where firstor second-line ovulation induction therapies have failed.

Conclusion: This review provides the best available evidence informing recommendations (along with clinical expertise and consumer preference) which provide clinicians with clear advice on best practice for the management of infertile women with PCOS.

The Australian & New Zealand Journal of Obstetrics & Gynaecology