How NaProTechnology compares with assisted reproductive technology

Abstract: La progresiva medicalización de la infertilidad en las últimas tres décadas se corresponde con una creciente difusión de las Tecnologías de Reproducción Asistida (TRA), que han dejado en la sombra, casi por completo, otros enfoques más fisiológicos del tratamiento de la infertilidad, que tienen menos riesgos, son más económicos y, a la vez, igualmente efectivos. Este trabajo presenta un enfoque sistemático e integrado: la NaProTecnología (NPT), que tiene como objetivo optimizar las condiciones fisiológicas en cada ciclo menstrual, para permitir, de esta forma, una concepción por métodos naturales. Este método se postula como una mejor solución para el tratamiento de la infertilidad, desde un punto de vista que no sólo es más ético, sino que, además, es compatible con otros puntos de vistas religiosos, médicos, sociales, legales y ambientales. Los gobiernos deberían promover y financiar la NPT y, al mismo tiempo, las sociedades médicas y científicas deberían diseñar estudios para comparar de una manera justa la tasa de éxito, los costos y las complicaciones de la NPT en contraposición al método TRA tradicional.


Relationship between Mast Cells, Endometriosis and Dysmenorrhea

Abstract: Case-based clinical presentation examining the role of mast cells in the pathophysiology of endometriosis and dysmenorrhea, presented by April Lind, MD (IFMCP, CFCMC, RHRI). Reviews mast-cell mediated inflammation, its relationship to endometriosis-associated pain and abnormal uterine bleeding, and functional-medicine considerations.


Seven-year-long screening of phthalate esters in clothing and textile products from a quality control laboratory

Abstract: The results of extensive yearly screening (2014–2020) of ortho-phthalate ester levels in textiles sent to a quality control laboratory by textile companies from southern European and northern African countries are presented. Six different regulated phthalates: benzyl butyl phthalate, di-butyl phthalate, di-(2-ethylhexyl) phthalate, di-iso-decyl phthalate, di-iso-nonyl phthalate and di-n-octyl phthalate, were measured in 4729 samples of textile materials from 10 different groups. Analyses were carried out according to the standard gas chromatography–mass spectroscopy procedure, as described by the US Consumer Product Safety Commission. The results revealed a high level of compliance with the European Union legislation (97.25%). In the group of noncompliant samples (total phthalate content >0.1% w/w), positive results were due to the presence of two or more phthalates in almost 60% of the cases. The phthalate esters most commonly detected were di-(2-ethylhexyl) phthalate, followed by di-iso-nonyl phthalate and di-butyl phthalate. In the group of compliant samples (total phthalate <0.1% w/w), the same frequency of occurrence was identified, but in this case most of the samples (almost 90%) contained only one phthalate. In addition, a growing tendency for a decrease in di-(2-ethylhexyl) phthalate levels and an increase in di-iso-nonyl phthalate and di-iso-decyl phthalate concentrations were detected throughout the study, due to replacement of the former by the latter in the use as a plasticizer. No significant differences between countries were noted with regard to the frequency or concentration of phthalates in the textile samples. The study findings contribute to advancing knowledge about the phthalate content of textiles and to evaluating and controlling the potential risks of exposure to these compounds.


A 10-Year Journey to Diagnosis With Endometriosis: An Autobiographical Case Report


Suspect and non-target screening of chemicals in clothing textiles by reversed-phase liquid chromatography/hybrid quadrupole-Orbitrap mass spectrometry

Abstract: AbstractThe global manufacturing of clothing is usually composed of multistep processes, which include a large number of chemicals. However, there is generally no information regarding the chemical content remaining in the finished clothes. Clothes in close and prolonged skin contact may thus be a significant source of daily human exposure to hazardous compounds depending on their ability to migrate from the textiles and be absorbed by the skin. In the present study, twenty-four imported garments on the Swedish market were investigated with respect to their content of organic compounds, using a screening workflow. Reversed-phase liquid chromatography coupled to electrospray ionization/high-resolution mass spectrometry was used for both suspect and non-target screening. The most frequently detected compound was benzothiazole followed by quinoline. Nitroanilines with suspected mutagenic and possible skin sensitization properties, and quinoline, a carcinogenic compound, were among the compounds occurring at the highest concentrations. In some garments, the level of quinoline was estimated to be close to or higher than 50,000 ng/g, the limit set by the REACH regulation. Other detected compounds were acridine, benzotriazoles, benzothiazoles, phthalates, nitrophenols, and organophosphates. Several of the identified compounds have logPand molecular weight values enabling skin uptake. This pilot study indicates which chemicals and compound classes should be prioritized for future quantitative surveys and control of the chemical content in clothing as well as research on skin transfer, skin absorption, and systemic exposure. The results also show that the current control and prevention from chemicals in imported garments on the Swedish market is insufficient.Graphical abstract


National Patient Survey 2021

National Patient Survey 2021

Human Fertilisation and Embryology Authority

Abstract:
# National Patient Survey 2021
Survey of UK fertility patients, 2 November – 7 December 2021
Published: April 2022
The key findings are published on this page with a statistical appendix available for download. A separate [Quality & Methodology report](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2021/patient-survey-2021-quality-and-methodology-report) provides details on survey methodology and patient profile.
[Download the underlying dataset as Excel Worksheet](https://www.hfea.gov.uk/media/lqwnb4lp/2022-04-07-national-patient-survey-underlying-data.xlsx "National Patient Survey Underlying Data").
## Table of contents
- [Main points](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2021/#main-points)
- [1\. Introduction](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2021/#introduction)
- [2\. Recent experience of fertility treatment](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2021/#recent-experience-of-fertility-treatment)
- [3\. Experience of speaking to a GP about fertility concerns](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2021/#experience-of-speaking-to-a-gp-about-fertility-concerns)
- [4\. Multiple embryo transfers](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2021/#multiple-embryo-transfers)
- [5\. Use of donor eggs, sperm, or embryos](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2021/#use-of-donor-eggs-sperm-or-embryos)
- [6\. Treatment add-ons](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2021/#treatment-add-ons)
- [7\. Knowledge of HFEA & Information/support sources](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2021/#knowledge-of-hfea-information-support-sources)
- [About ou...


Rapport annuel d'AMP Vigilance 2021

Rapport annuel d'AMP Vigilance 2021

Abstract: Rapport annuel d'AMP Vigilance 2021 publié par l'Agence de la biomédecine. Annual AMP (Medically Assisted Reproduction) Vigilance Report 2021 from the French Agence de la biomédecine.


JSOG-ART Annual Report 2021 (体外受精・胚移植等の臨床実施成績 2021年)

Abstract: 日本産科婦人科学会 体外受精・胚移植等の臨床実施成績 2021年. ENGLISH SUMMARY: JSOG ART annual registry report for 2021 from the Japan Society of Obstetrics and Gynecology. Reports IVF, ICSI, and frozen-embryo-transfer cycle volumes and outcomes. Mandatory professional-society reporting from all JSOG-registered ART facilities in Japan.


Abstract:
1. BMC Pregnancy Childbirth. 2022 May 2;22(1):381. doi:
10.1186/s12884-022-04693-0.

Leukocyte telomere dynamics across gestation in uncomplicated pregnancies and
associations with stress.

Panelli DM(1), Leonard SA(2), Wong RJ(3), Becker M(3)(4)(5), Mayo JA(3), Wu
E(2), Girsen AI(2), Gotlib IH(6), Aghaeepour N(3)(4)(5), Druzin ML(2), Shaw
GM(3), Stevenson DK(3), Bianco K(2).

Author information:
(1)Department of Obstetrics and Gynecology, Stanford University, 453 Quarry
Road, Palo Alto, CA, 94304, USA. dpanelli@stanford.edu.
(2)Department of Obstetrics and Gynecology, Stanford University, 453 Quarry
Road, Palo Alto, CA, 94304, USA.
(3)Department of Pediatrics, Stanford University, Stanford, CA, USA.
(4)Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford
University, Stanford, CA, USA.
(5)Department of Biomedical Data Science, Stanford University, Stanford, CA,
USA.
(6)Department of Psychology, Stanford University, Stanford, CA, USA.

BACKGROUND: Short leukocyte telomere length is a biomarker associated with
stress and morbidity in non-pregnant adults. Little is known, however, about
maternal telomere dynamics in pregnancy. To address this, we examined changes in
maternal leukocyte telomere length (LTL) during uncomplicated pregnancies and
explored correlations with perceived stress.
METHODS: In this pilot study, maternal LTL was measured in blood collected from
nulliparas who delivered live, term, singleton infants between 2012 and 2018 at
a single institution. Participants were excluded if they had diabetes or
hypertensive disease. Samples were collected over the course of pregnancy and
divided into three time periods: < 200/7 weeks (Timepoint 1); 201/7 to 366/7
weeks (Timepoint 2); and 370/7 to 9-weeks postpartum (Timepoint 3). All
participants also completed a survey assessing a multivariate profile of
perceived stress at the time of enrollment in the first trimester. LTL was
measured using quantitative polymerase chain reaction (PCR). Wilcoxon
signed-rank tests were used to compare LTL differences within participants
across all timepoint intervals. To determine whether mode of delivery affected
LTL, we compared postpartum Timepoint 3 LTLs between participants who had
vaginal versus cesarean birth. Secondarily, we evaluated the association of the
assessed multivariate stress profile and LTL using machine learning analysis.
RESULTS: A total of 115 samples from 46 patients were analyzed. LTL (mean ± SD),
expressed as telomere to single copy gene (T/S) ratios, were: 1.15 ± 0.26,
1.13 ± 0.23, and 1.07 ± 0.21 for Timepoints 1, 2, and 3, respectively. There
were no significant differences in LTL between Timepoints 1 and 2 (LTL T/S
change - 0.03 ± 0.26, p = 0.39); 2 and 3 (- 0.07 ± 0.29, p = 0.38) or Timepoints
1 and 3 (- 0.07 ± 0.21, p = 0.06). Participants who underwent cesareans had
significantly shorter postpartum LTLs than those who delivered vaginally (T/S
ratio: 0.94 ± 0.12 cesarean versus 1.12 ± 0.21 vaginal, p = 0.01). In secondary
analysis, poor sleep quality was the main stress construct associated with
shorter Timepoint 1 LTLs (p = 0.02) and shorter mean LTLs (p = 0.03).
CONCLUSIONS: In this cohort of healthy pregnancies, maternal LTLs did not
significantly change across gestation and postpartum LTLs were shorter after
cesarean than after vaginal birth. Significant associations between sleep
quality and short LTLs warrant further investigation.

© 2022. The Author(s).

DOI: 10.1186/s12884-022-04693-0
PMCID: PMC9063069
PMID: 35501726 [Indexed for MEDLINE]

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


Abstract:
1. Fertil Steril. 2022 Jan;117(1):124-130. doi: 10.1016/j.fertnstert.2021.08.035.
Epub 2021 Sep 15.

Prevalence and performance of private equity-affiliated fertility practices in
the United States.

Borsa A(1), Bruch JD(2).

Author information:
(1)Department of Sociomedical Sciences, Columbia University Mailman School of
Public Health, New York, New York. Electronic address:
asb2266@cumc.columbia.edu.
(2)Department of Health Care Policy, Harvard Medical School, Boston,
Massachusetts.

Comment in
Fertil Steril. 2022 Jan;117(1):131-132. doi:
10.1016/j.fertnstert.2021.11.001.

OBJECTIVE: To quantify the proportion of annual assisted reproductive technology
(ART) cycles performed at private equity-affiliated fertility practices and to
test for differences in services and success rates between private
equity-affiliated and nonaffiliated practices.
DESIGN: Cross-sectional analysis of national data set.
SETTING: Not applicable.
PATIENT(S): None.
INTERVENTION(S): Not applicable.
MAIN OUTCOME MEASURE(S): The primary outcome measures were the volume of ART
cycles performed, the percentage of retrievals resulting in live births, and the
percentage of transfers resulting in live births. The secondary outcomes
included the median income of the practice location, the use of preimplantation
genetic testing, the clinical service availability, and the patient reasons for
seeking treatment.
RESULT(S): Of the practices listed on the Centers for Disease Control's 2018
Fertility Clinic Success Rates Report, 14.7% had a private equity affiliation.
Of the 305,883 ART cycles performed in 2018, 29.3% (89,535) occurred at private
equity-affiliated practices. Patients at private equity-affiliated practices
were 6.75% (95% confidence interval [CI], -10.15%, -3.36%) less likely to
initiate a cycle due to male factor infertility, and 10.60% (95% CI, 3.49,
17.76) more likely to use preimplantation genetic testing before embryo
transfer. No statistically significant differences were found in success rates
among women aged <35 years. The average median household income (standard error)
in zip codes with private equity-affiliated practices compared with
nonaffiliated practices was $83,610 ($35,990) and $72,161 ($32,314),
respectively.
CONCLUSION(S): A major portion of fertility practices in the United States are
private equity-affiliated, and these practices perform an even greater portion
of ART cycles in the United States each year. Fertility appears to be the
medical specialty with the greatest market share owned by private equity. Our
findings corroborate preliminary research, which forecasts the increasing
involvement and consolidation by private equity in fertility. Future research
should continue monitoring for differences in outcomes, financing, case mix,
service use, and accessibility.

Copyright © 2021 American Society for Reproductive Medicine. Published by
Elsevier Inc. All rights reserved.

DOI: 10.1016/j.fertnstert.2021.08.035
PMCID: PMC8714667
PMID: 34538462 [Indexed for MEDLINE]


Early-Life Exposure to Formaldehyde through Clothing

Abstract: Clothes contain a wide range of chemicals, some of them potentially hazardous. Recently, there has been a growing interest in eco-friendly clothing, including the use of organic cotton. However, the process of eco-friendly fabric production does not exclude the use of toxic substances, such as formaldehyde, a known human carcinogen. The present investigation was aimed at determining the presence of formaldehyde in eco-friendly and conventional clothing of pregnant women, babies, and toddlers from the Catalan (Spain) market. The potential effects of washing were also investigated by comparing the reduction of formaldehyde in unwashed and washed clothing. Formaldehyde was detected in 20% of samples, with a mean level of 8.96 mg/kg. Formaldehyde levels were surprisingly higher in eco-friendly than in regular garments (10.4 vs. 8.23 mg/kg). However, these differences were only significant (p < 0.05) for bras (11.6 vs. 7.46 mg/kg) and panties (27.1 vs. 6.38 mg/kg) of pregnant women. Dermal exposure and health risks were assessed for three vulnerable population groups: pregnant women, babies, and toddlers. In general, exposure was higher in babies (up to 1.11 × 10−3 mg/kg/day) than in other groups (2.58 × 10−4 and 4.50 × 10−3 mg/kg/day in pregnant women and toddlers, respectively). However, both non-carcinogenic and carcinogenic risks were below the safety limits (<1 and <10−5, respectively) according to national regulations. Notwithstanding, although formaldehyde levels were below the legal limits (<75 mg/kg) and health risks were within acceptable ranges, clothing may contain other toxic substances in addition to formaldehyde, thus increasing the risks. Finally, since no formaldehyde was detected in washed textile samples, a safe and simple practice for the consumers is to wash clothing before the first use.


Sperm-friendly lubricant: Fact or fiction

Abstract: OBJECTIVE: To assess the effects of "sperm-friendly" coital lubricants on sperm motility. METHODS: This study compared the effects of five lubricants (Optilube®, Pre-Seed®, Yes Baby®, olive oil, and egg white) on sperm motility in 60 normozoospermic semen samples obtained from men attending a private fertility clinic. Samples were exposed to each of the lubricants, with untreated samples serving as controls, and were examined microscopically at four defined time-points from 2 to 72 h after liquefaction. Sperm motility was graded according to World Health Organization criteria. RESULTS: With the exception of egg white, all lubricants caused significant (P < 0.001) reductions in sperm forward progression compared with untreated controls until 24 h after liquefaction. Furthermore, between-group comparisons of the commercially available lubricants revealed statistically significant differences in forward progression motility: Pre-Seed® was superior to Optilube® (P < 0.001), which in turn was superior to Yes Baby® (P < 0.001) at 2-4 h after exposure. Significance (P < 0.001) between Pre-Seed® and Yes Baby® was maintained until 24 h. CONCLUSION: Although spermatozoa exposed to Pre-Seed® demonstrated greater motility than spermatozoa exposed to Yes Baby®, claims that these lubricants are sperm-friendly were refuted. Conversely, egg white was shown to be a sperm-friendly lubricant for couples who are trying to conceive.

International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics


ESHRE guideline: endometriosis

ESHRE guideline: endometriosis

ESHRE Endometriosis Guideline Development Group


Female reproductive dysfunctions and the gut microbiota


Allergies caused by textiles and their control


Effects of low energy availability on female reproductive function

Yu Yamamoto

Research and Development Division, Kagome, Nasushiobara, Japan. Email: Yu_Yamamoto@kagome.co.jp.

Abstract:
BACKGROUND: It is known that metabolic and nutritional disturbances induce reproductive dysfunction in females. The main cause of these alterations is reduced gonadotrophin-releasing hormone (GnRH) secretion from the hypothalamus, and the underlying mechanisms have gradually been elucidated.

METHODS: The present review summarizes current knowledge about the effects of nutrition/metabolism on reproductive functions, especially focusing on the GnRH regulation system.

MAIN FINDINGS: Various central and peripheral factors are involved in the regulation of GnRH secretion, and alterations in their activity combine to affect GnRH neurons. Satiety-related factors, i.e., leptin, insulin, and alpha-melanocyte-stimulating hormone, directly and indirectly stimulate GnRH secretion, whereas orexigenic factors, i.e., neuropeptide Y, Agouti-related protein, orexin, and ghrelin, attenuate GnRH secretion. In addition, kisspeptin, which is a potent positive regulator of GnRH, expression is reduced by metabolic and nutritional disturbances.

CONCLUSION: These neuroendocrine systems may be defensive mechanisms, which help organisms to survive adverse conditions by temporarily suppressing reproduction.


Rapport annuel d'activité 2021 - Agence de la biomédecine

Abstract: Rapport annuel d'activité 2021 de l'Agence de la biomédecine. Annual activity report covering Agence de la biomédecine activities including AMP (Medically Assisted Reproduction) registry operations for 2021. Provides governance and operational context for the French national ART registry.


Current Insights and Latest Updates in Sperm Motility and Associated Applications in Assisted Reproduction

Abstract: Spermatozoon is a motile cell with a special ability to travel through the woman's reproductive tract and fertilize an oocyte. To reach and penetrate the oocyte, spermatozoa should possess progressive motility. Therefore, motility is an important parameter during both natural and assisted conception. The global trend of progressive reduction in the number and motility of healthy spermatozoa in the ejaculate is associated with increased risk of infertility. Therefore, developing approaches for maintaining or enhancing human sperm motility has been an important area of investigation. In this review we discuss the physiology of sperm, molecular pathways regulating sperm motility, risk factors affecting sperm motility, and the role of sperm motility in fertility outcomes. In addition, we discuss various pharmacological agents and biomolecules that can enhance sperm motility in vitro and in vivo conditions to improve assisted reproductive technology (ART) outcomes. This article opens dialogs to help toxicologists, clinicians, andrologists, and embryologists in understanding the mechanism of factors influencing sperm motility and various management strategies to improve treatment outcomes.

Reproductive sciences (Thousand Oaks, Calif.)


DIR Jahrbuch 2021 (Deutsches IVF-Register Annual Report 2021)

Abstract: Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2021. 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).


Understanding the effect of endometrial microbiome composition on implantation rates


Assisted reproductive technology in Japan: A summary report for 2019 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 2019, published by the Ethics Committee of the Japan Society of Obstetrics and Gynecology (JSOG).


Wang C, Gu Y, Zhou J, Zang J, Ling X, Li H, Hu L, Xu B, Zhang B, Qin N, Lv H, Duan W, Jiang Y, He Y, Jiang T, Chen C, Han X, Zhou K, Xu B, Liu X, Tao S, Jiang Y, Du J, Dai J, Diao F, Lu C, Guo X, Huo R, Liu J, Lin Y, Xia Y, Jin G, Ma H, Shen H, Hu Z

Abstract:
1. Nat Med. 2022 Dec;28(12):2646-2653. doi: 10.1038/s41591-022-02108-3. Epub 2022
Dec 15.

Leukocyte telomere length in children born following blastocyst-stage embryo
transfer.

Wang C(#)(1)(2)(3), Gu Y(#)(1)(2), Zhou J(#)(2), Zang J(#)(2), Ling X(#)(1)(4),
Li H(#)(1)(5), Hu L(6), Xu B(7), Zhang B(8), Qin N(1)(2), Lv H(1)(9), Duan W(3),
Jiang Y(1)(2), He Y(1)(2), Jiang T(1)(10), Chen C(2), Han X(1)(2), Zhou K(1)(2),
Xu B(1)(2), Liu X(1)(2), Tao S(1)(2), Jiang Y(1)(2), Du J(1)(2), Dai J(1)(2),
Diao F(1)(11), Lu C(1)(12), Guo X(1), Huo R(1), Liu J(1)(9)(11), Lin
Y(1)(9)(13), Xia Y(1)(12), Jin G(1)(2)(9), Ma H(1)(2)(9), Shen H(1)(2)(9), Hu
Z(14)(15)(16).

Author information:
(1)State Key Laboratory of Reproductive Medicine, Nanjing Medical University,
Nanjing, Jiangsu, China.
(2)Department of Epidemiology, Center for Global Health, School of Public
Health, Nanjing Medical University, Nanjing, Jiangsu, China.
(3)Department of Bioinformatics, School of Biomedical Engineering and
Informatics, Nanjing Medical University, Nanjing, Jiangsu, China.
(4)Department of Reproduction, The Affiliated Obstetrics and Gynecology Hospital
of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital,
Nanjing, Jiangsu, China.
(5)Reproductive Genetic Center, The Affiliated Suzhou Hospital of Nanjing
Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical
University, Suzhou, Jiangsu, China.
(6)Department of Reproduction, Changzhou Maternity and Child Health Care
Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou,
Jiangsu, China.
(7)Reproductive Medicine Center, Tongji Hospital, Tongji Medicine College,
Huazhong University of Science and Technology, Wuhan, Hubei, China.
(8)Center for Reproductive Medicine, The Maternal and Child Health Hospital of
Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China.
(9)State Key Laboratory of Reproductive Medicine (Suzhou Centre), The Affiliated
Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu
School, Nanjing Medical University, Suzhou, Jiangsu, China.
(10)Department of Biostatistics, Center for Global Health, School of Public
Health, Nanjing Medical University, Nanjing, Jiangsu, China.
(11)Clinical Center of Reproductive Medicine, The First Affiliated Hospital of
Nanjing Medical University, Nanjing Medical University, Nanjing, Jiangsu, China.
(12)Key Laboratory of Modern Toxicology of Ministry of Education, School of
Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
(13)Department of Maternal, Child and Adolescent Health, School of Public
Health, Nanjing Medical University, Nanjing, Jiangsu, China.
(14)State Key Laboratory of Reproductive Medicine, Nanjing Medical University,
Nanjing, Jiangsu, China. zhibin_hu@njmu.edu.cn.
(15)Department of Epidemiology, Center for Global Health, School of Public
Health, Nanjing Medical University, Nanjing, Jiangsu, China.
zhibin_hu@njmu.edu.cn.
(16)State Key Laboratory of Reproductive Medicine (Suzhou Centre), The
Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal
Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China.
zhibin_hu@njmu.edu.cn.
(#)Contributed equally

Comment in
Nat Med. 2022 Dec;28(12):2476-2477. doi: 10.1038/s41591-022-02098-2.

Perinatal and childhood adverse outcomes associated with assisted reproductive
technology (ART) has been reported, but it remains unknown whether the initial
leukocyte telomere length (LTL), which is an indicator of age-related phenotypes
in later life, is affected. Here, we estimated the LTLs of 1,137 individuals
from 365 families, including 202 children conceived by ART and 205 children
conceived spontaneously from two centers of the China National Birth Cohort,
using whole-genome sequencing (WGS) data. One-year-old children conceived by ART
had shorter LTLs than those conceived spontaneously (beta, -0.36;
P = 1.29 × 10-3) after adjusting for plurality, sex and other potential
confounding factors. In particular, blastocyst-stage embryo transfer was
associated with shorter LTL (beta, -0.54, P = 2.69 × 10-3) in children conceived
by ART. The association was validated in 586 children conceived by ART from five
centers using different LTL quantification methods (that is, WGS or qPCR).
Blastocyst-stage embryo transfer resulted in shorter telomere lengths in mice at
postnatal day 1 (P = 2.10 × 10-4) and mice at 6 months (P = 0.042). In vitro
culturing of mice embryos did not result in shorter telomere lengths in the late
cleavage stage, but it did suppress telomerase activity in the early blastocyst
stage. Our findings demonstrate the need to evaluate the long-term consequences
of ART, particularly for aging-related phenotypes, in children conceived by ART.

© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.

DOI: 10.1038/s41591-022-02108-3
PMID: 36522605 [Indexed for MEDLINE]


Face mask—A potential source of phthalate exposure for human

Wenchao Han

Department of Pediatrics, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao 266071, China. Electronic address: hanwenchaodr@outlook.com.

Junhao Chen

Chinese Academy of Medical Sciences & Peking Union Medical College

Abstract: Face masks are necessary for fighting against the coronavirus disease 2019 around the world. As the face mask is usually made from polymers and phthalates are widely-used additives into the polymers, the face mask could be a potential source of phthalate exposure to humans. However, limited knowledge is available on the occurrence and risks of the phthalates from the face mask. In this study, twelve phthalates were determined in 56 mask samples collected from different countries. The phthalates were detected in all the samples with total levels ranging from 115 ng/g to 37,700 ng/g. Estimated daily intakes (EDIs) of the phthalates from the masks ranged from 3.71 to 639 ng/kg-bw/day, and the EDIs of the phthalates from masks for toddlers were approximately 4-5 times higher than those for adults. Non-carcinogenic risks in relation to the phthalates in masks were found to be within safe levels, yet 89.3% of the mask samples exhibited potential carcinogenic effects to humans. The extent of the risks for wearing masks located at a moderate level comparing with other skin-contacted products. This study unveiled a potential source of phthalate exposure to human, and indicated necessity of managing types and levels of additives in the face masks.


Patch test results to extracts of synthetic garments in textile dye positive patients

Abstract: AbstractBackgroundDisperse dyes (DDs) are the most prevalent causes of textile‐related allergic contact dermatitis and are used for colouring synthetic textile materials based on fibres such as polyester, acrylic, acetate and polyamide. Eight DDs are included in a textile dye mix (TDM) 6.6% petrolatum (pet.) in the European baseline patch test series.ObjectivesThe aim of this study was to patch test TDM 6.6% pet. positive individuals with the extracts of synthetic fibre clothes that do not contain any of the pure DDs present in the TDM 6.6% to study the reactivity pattern.MethodsSeventy‐three TDM‐positive former patients tested between 2012 and 2017 at the Department of Occupational and Environmental Dermatology in Malmö, Sweden were invited to join the study, 10 participated. Twenty‐four textile items (collected in nine countries in Europe, Asia and North America in 2012) were extracted in dichloromethane. The TDM 6.6% was patch tested simultaneously with the 24 textile item preparations in petrolatum made from the extracts. Prior to patch testing the participants filled the 7‐question questionnaire regarding possible symptoms from textile exposure.ResultsTen individuals, agreed to join the study. Eight of them reacted to TDM 6.6%. Nine participants reacted to 20 of 24 extracts. One reacted to 19 extracts, another to 14, 3 to 5 extracts, 1 to 4, 1 to 3 extracts and 2 to 2 extracts. One was negative to all tested preparations including TDM 6.6%. The participants mainly reacted to six textile extracts. All controls tested negatively to tested extracts. Four individuals of the 10 TDM‐allergic individuals previously had had problems after wearing clothes. Four out of the 10 participants had had atopic eczema in childhood. All women had dyed their hair with permanent hair dyes but none of the males.ConclusionTDM‐positive patients react to textile extracts made from synthetic garments, even if they do not contain any of the pure DDs present in TDM 6.6%. More studies are needed to pin‐point the culprit haptens in these extracts.


In couples with infertility, is natural procreative technology successful in achieving live birth?

Abstract: Mankato Family Medicine Residency, University of Minnesota, Mankato, MN The corresponding author is Robert D. Jeske; [email protected]. The authors declare no conflicts of interest.


Chorioamnionitis and neonatal outcomes

Chorioamnionitis and neonatal outcomes

Abstract: Chorioamnionitis or intrauterine inflammation is a frequent cause of preterm birth. Chorioamnionitis can affect almost every organ of the developing fetus. Multiple microbes have been implicated to cause chorioamnionitis, but "sterile" inflammation appears to be more common. Eradication of microorganisms has not been shown to prevent the morbidity and mortality associated with chorioamnionitis as inflammatory mediators account for continued fetal and maternal injury. Mounting evidence now supports the concept that the ensuing neonatal immune dysfunction reflects the effects of inflammation on immune programming during critical developmental windows, leading to chronic inflammatory disorders as well as vulnerability to infection after birth. A better understanding of microbiome alterations and inflammatory dysregulation may help develop better treatment strategies for infants born to mothers with chorioamnionitis.


"Trends in Egg, Sperm and Embryo Donation 2020"

Human Fertilisation and Embryology Authority

Abstract:
# Trends in egg, sperm and embryo donation 2020
Statistics on donation and donor treatments in the UK fertility sector
Published: November 2022
[Download the underlying dataset as .xlsx](https://www.hfea.gov.uk/media/ycjb2gnm/trends-in-egg-sperm-and-embryo-donation-2020-underlying-dataset.xlsx "Trends in egg, sperm and embryo donation 2020 - underlying dataset")
## Table of contents
- [Main points](https://www.hfea.gov.uk/about-us/publications/research-and-data/trends-in-egg-sperm-and-embryo-donation-2020/#main-points)
- [Foreword](https://www.hfea.gov.uk/about-us/publications/research-and-data/trends-in-egg-sperm-and-embryo-donation-2020/#foreword)
- [Section 1. Use of donor eggs, sperm and embryos has increased](https://www.hfea.gov.uk/about-us/publications/research-and-data/trends-in-egg-sperm-and-embryo-donation-2020/#section-1)
- [Section 2. Donor registrations have increased, though access to donors of ethnic minority backgrounds varies](https://www.hfea.gov.uk/about-us/publications/research-and-data/trends-in-egg-sperm-and-embryo-donation-2020/#section-2)
- [Section 3. Treatments using donor eggs, sperm and embryos less commonly funded by NHS](https://www.hfea.gov.uk/about-us/publications/research-and-data/trends-in-egg-sperm-and-embryo-donation-2020/#section-3)
- [Section 4. Donor eggs can increase birth rates for older patients](https://www.hfea.gov.uk/about-us/publications/research-and-data/trends-in-egg-sperm-and-embryo-donation-2020/#section-4)
- [Section 5. From 2023, donor-conceived people will be able to access information on their donors](https://www.hfea.gov.uk/about-us/publications/research-and-data/trends-in-egg-sperm-and-embryo-donation-2020/#section-5)
- [Section 6. Characteristics of egg and sperm donors have changed over time](https://www.hfea.gov.uk/about-us/publications/research-and-data/trends-in-egg-sperm-and-embryo-donation-2020/#section-6)
- [About our data](https://www.hfea.gov.uk/about-us/publications/research-and-data/trends-in-egg-sp...


Optimizing natural fertility: a committee opinion

Practice Committee of the American Society for Reproductive Medicine

Abstract: This committee opinion provides practitioners with suggestions for optimizing the likelihood of achieving pregnancy in couples or individuals attempting conception who have no evidence of infertility. This document replaces the document of the same name previously published in 2013 (Fertil Steril 2013;100:631-7).


Thyroid autoimmunity and its negative impact on female fertility and maternal pregnancy outcomes

Abstract: Thyroid autoimmunity (TAI) is commonly defined as the presence of thyroperoxidase antibodies (TPOAbs) and/or thyroglobulin antibodies (TgAbs), which predisposes an individual to hypothyroidism. TAI affects nearly 10% of women of reproductive age and evokes great interest from clinicians because of its potentially negative impact on female fertility and pregnancy course. In this mini-review, we review the current literature concerning the influence of TPOAb or TPOAb/TgAb positivity without thyroid dysfunction on reproduction. TAI may negatively affect female fertility; several studies have found an increased prevalence of TAI in infertile women, especially in those with unexplained infertility and polycystic ovary syndrome. According to some observations, TAI might also be connected with premature ovarian insufficiency and endometriosis. The relationship between TAI and an increased risk of pregnancy loss is well documented. The pathophysiological background of these observations remains unclear, and researchers hypothesize on the direct infiltration of reproductive organs by thyroid antibodies, co-existence of TAI with other autoimmune diseases (either organ specific or systemic), immunological dysfunction leading to inhibition of immune tolerance, and relative thyroid hormone deficiency. Interestingly, in the current literature, better outcomes of assisted reproductive technology in women with TAI have been reported compared with those reported in earlier publications. One plausible explanation is the more widespread use of the intracytoplasmic sperm injection method. The results of randomized clinical trials have shown that levothyroxine supplementation is ineffective in preventing adverse pregnancy outcomes in women with TAI, and future research should probably be directed toward immunotherapy.


Relative Energy Deficiency in Sport (RED-S): Scientific, Clinical, and Practical Implications for the Female Athlete

Abstract:
PROBLEM: If athletes develop low energy availability (LEA), it can lead to a Relative Energy Deficiency in Sport (RED-S) syndrome which has severe health consequences if not treated.

METHODOLOGY: A narrative review of the most recent and pertinent literature on the topic, with special emphasis on women.

RESULTS: In assessing the current literature, we have synthesized: i) the scientific implications of LEA and RED-S, ii) the clinical manifestations of the conditions currently available for detection, as well as iii) the practical implications for healthcare and support for female athletes and teams in planning intervention or prevention strategies (maintaining EA >45 kcal/kg FFM/day).

DISCUSSION: The 'Female Athlete Triad" emerged in the 1990s as researchers understood more of the etiological adaptation of female athlete health to sports training. In the last 10 years, the scientific community has recognized that the 'Triad' approach was too narrow in focus, and the broader concept of RED-S emerged. Both the Triad and RED-S are consequences of a frequently prevalent LEA in athletes (<30 kcal/kg FFM/day). Developing LEA and RED-S compromises training adaptation, performance capacity, and health in athletes. For these reasons, it is critical that an athlete's support team recognize the behaviors that may indicate RED-S evolution. In this way, we can assist female athletes in reaching their full potential in sports while protecting their health.

PROBLEM: Kommt es bei männlichen oder weiblichen Athleten zu einer dauerhaft niedrigen Energieverfügbarkeit (low energy availability, LEA), steigt das Risiko eines Relative Energy Deficiency in Sports (RED-S) Syndroms, welches unbehandelt schwerwiegende kurz- wie langfristige gesundheitliche Konsequenzen haben kann.

METHODIK: Ein narratives Review der aktuellsten und relevantesten Literatur mit besonderem Fokus auf weibliche Betroffene.

RESULTATE: Aus der verfügbaren Literatur haben wir i) wissenschaftliche Implikationen von LEA und RED-S, ii) klinische Manifestationen und iii) praktische Implikationen für die medizinische Behandlung, Unterstützung betroffener Teams, sowie präventive Strategien herausgearbeitet.

DISKUSSION: In den 1990er Jahren erfasste mit zunehmendem Verständnis um die frauen-spezifischen Anpassungen an sportliche Aktivität das Phänomen der “Female Athlete Triad” die Aufmerksamkeit von Wissenschaftlern und Medizinern. In der vergangenen 10 Jahren zeigte sich, dass der “Triad”-Ansatz zu kurz greift und es wurde stattdessen das breiter gefasste Konzept des RED-S etabliert. Sowohl die “Female Athlete Triad”, als auch RED-S sind letztendlich Konsequenzen der häufig prävalenten LEA in Athletinnen mit weitreichenden Konsequenzen auf die Trainingsadaptation, Wettkampfleistung und kurz-, wie langfristige Gesundheit der Betroffenen. Aus diesem Grund ist das Erkennen von Verhaltensweisen, welche auf ein RED-S hindeuten durch Trainer und weiterer Stakeholder einer Athletin beziehungsweise eines Teams essenziell für eine gesundheitsund leistungserhaltende Betreuung von betroffenen Athletinnen.


Association between Endometrial Polyps and Chronic Endometritis: Is It Time for a  Paradigm Shift in the Pathophysiology of Endometrial Polyps in Pre-Menopausal  Women? Results of a Systematic Review and Meta-Analysis

Pantaleo Greco

Department of Translational and for Romagna Medicine, University of Ferrara, 44121 Ferrara, Italy

Ettore Cicinelli

Unit of Obstetrics and Gynecology, Department of Biomedical and Human Oncologic Science, University of Bari, 70124 Bari, Italy

Abstract:
Background: Chronic endometritis (CE) and endometrial polyps (EPs) are common conditions in reproductive age women. CE is an infectious disorder of the endometrium characterized by signs of chronic inflammation at hysteroscopic and histological analyses. EPs are abnormal endometrial growths containing glands, stroma and blood vessels projecting from the lining of the uterus. During the last years, different authors have investigated the correlation between CE and EPs, with controversial results. The aim of this study was to summarize available evidence on the potential correlation between CE and EPs.
Design: Systematic literature review and meta-analysis.

Methods: Observational-studies were identified by searching electronic databases from their inception to September 2021. Only studies on pre-menopausal women were included. Statistical analysis was performed using MedCalc 16.4.3 (Ostend, Belgium) and Review Manager version 5.3 (Nordic Cochrane Centre, Cochrane Collaboration). The summary measures were reported as pooled proportion or odds ratio (OR) with 95% confidence interval (CI). The primary outcome was to evaluate the prevalence of CE in women with EPs. The secondary outcome was to determine the prevalence of CD-138-positive EPs among EPs. Tertiary outcomes were to compare the prevalence of CE in women with EPs versus women with a non-polypoid endometrium and to compare the prevalence of CE in women with a single EP versus women with multiple EPs.

Results: Eight observational studies (n = 3225 patients) were included in quantitative synthesis. Pooled prevalence of CE among women with EPs was 51.35% (95% CI, 27.24-75.13%). Pooled proportion of CD-138-positive EPs among EPs was 70.73% (95% CI, 55.73-83.68%). Women with EPs showed higher prevalence of CE compared to women without EPs (OR 3.07, 95% CI 1.59-5.95). Women with ≥3 EPs had higher prevalence of CE then women with a single EP (OR 3.43, 95% CI 1.83-6.46).

Conclusions: In pre-menopausal women, CE and EPs may have a dependent relationship and may represent two consequent steps of a common pathological process.


Increased Serum Prolactin and Excessive Daytime Sleepiness: An Attempt of  Proof-of-Concept Study

Fabio Pizza

Istituto delle Scienze Neurologiche di Bologna

Abstract: The objectives of this study were: (1) to identify subjects with hyperprolactinemia in a clinical sample of patients; (2) to compare the neurologic, psychiatric, and sleep conditions found in patients subgrouped by excessive daytime sleepiness (EDS) and hyperprolactinemia; and (3) to identify patients with hyperprolactinemia and EDS not supported by the presence of any other neurologic, psychiatric, or sleep disorder, or substance/medication use. A retrospective chart review of inpatients was carried out in order to identify all patients in whom the prolactin (PRL) serum levels were determined. A total of 130 subjects were retrieved: 55 had increased levels of PRL, while the remaining 75 participants had normal PRL levels. EDS was reported by 32 (58.2%) participants with increased PRL and 34 (45.3%) with normal PRL. Obstructive sleep apnea or other sleep or neurologic/psychiatric conditions could explain EDS in all participants with normal PRL. Among subjects with increased PRL, eight had no other neurologic/psychiatric or sleep disorder (or drug) potentially causing EDS; these participants, at polysomnography, had time in bed, sleep period time, and total sleep time longer than those with EDS associated to another condition. These findings can be considered as a preliminary indication of a role of hyperprolactinemia in EDS and represent a basis for future controlled studies able to test this hypothesis in a reliable, objective, and methodologically more appropriate way.


Immunology and Immunotherapy of Endometriosis

Marta Hoffmann-Młodzianowska

Laboratory of Molecular Oncology and Innovative Therapies, Department of Oncology, Military Institute of Medicine, 04-141 Warsaw, Poland

Claudine Kieda

Centre National de la Recherche Scientifique

Radosław B Maksym

Postgraduate School of Molecular Medicine

Abstract: Endometriosis is one of the most common gynecological and systemic diseases, with a remarkable immune background. Patients suffer from pain and fertility reduction. Due to the distinct immune component, an immunotherapeutic approach may gain importance in the future. In endometriosis, shifts in the cell fractions of the immune system are well known. Moreover, hypoxia concomitant with inflammation causes a disturbed immune response. The removal of endometriosis has a therapeutic effect, normalizes the immune disorders, and remains the most effective causative treatment in terms of pain and infertility. A key issue is whether a similar effect can be achieved for fertility with non-invasive immunotherapy where surgery is inadvisable or cannot be performed for various reasons. Numerous immunotherapy trials, including vaccines, were conducted on animals only, although the research is encouraging. Among the promising methods of non-specific immunotherapy is the administration of an ethiodized oil contrast. Moreover, due to the significant successes of immunotherapy in oncology, the possibility of immunotherapy affecting NK cells has been postulated. NK cells are responsible for the surveillance and apoptosis of ectopic cells. Expanding the arsenal of endometriosis treatment by immunotherapy is promising due to the significant contribution of immunological factors and the limitations of current treatment methods.


The Role of Genital Tract Microbiome in Fertility: A Systematic Review

Abstract: The human microbiome plays a crucial role in determining the health status of every human being, and the microbiome of the genital tract can affect the fertility potential before and during assisted reproductive treatments (ARTs). This review aims to identify and appraise studies investigating the correlation of genital microbiome to infertility. Publications up to February 2021 were identified by searching the electronic databases PubMed/MEDLINE, Scopus and Embase and bibliographies. Only full-text original research articles written in English were considered eligible for analysis, whereas reviews, editorials, opinions or letters, case studies, conference papers, and abstracts were excluded. Twenty-six articles were identified. The oldest studies adopted the exclusive culture-based technique, while in recent years PCR and RNA sequencing based on 16S rRNA were the most used technique. Regardless of the anatomical site under investigation, the Lactobacillus-dominated flora seems to play a pivotal role in determining fertility, and in particular Lactobacillus crispatus showed a central role. Nonetheless, the presence of pathogens in the genital tract, such as Chlamydia trachomatis, Gardnerella vaginalis, Ureaplasma species, and Gram-negative stains microorganism, affected fertility also in case of asymptomatic bacterial vaginosis (BV). We failed to identify descriptive or comparative studies regarding tubal microbiome. The microbiome of the genital tract plays a pivotal role in fertility, also in case of ARTs. The standardization of the sampling methods and investigations approaches is warranted to stratify the fertility potential and its subsequent treatment. Prospective tubal microbiome studies are warranted.

International Journal of Molecular Sciences


Metabolic Syndrome and PCOS: Pathogenesis and the Role of Metabolites

Weixuan Chen

Ministry of Education of the People's Republic of China

Abstract: Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases among women of reproductive age and is associated with many metabolic manifestations, such as obesity, insulin resistance (IR) and hyperandrogenism. The underlying pathogenesis of these metabolic symptoms has not yet been fully elucidated. With the application of metabolomics techniques, a variety of metabolite changes have been observed in the serum and follicular fluid (FF) of PCOS patients and animal models. Changes in metabolites result from the daily diet and occur during uncommon physiological routines. However, some of these metabolite changes may provide evidence to explain possible mechanisms and new approaches for prevention and therapy. This article reviews the pathogenesis of PCOS metabolic symptoms and the relationship between metabolites and the pathophysiology of PCOS. Furthermore, the potential clinical application of some specific metabolites will be discussed.


Ranking lifestyle risk factors for cervical cancer among Black women: A case-control study from Johannesburg, South Africa

Abstract:
Background: Aside from human papillomavirus (HPV), the role of other risk factors in cervical cancer such as age, education, parity, sexual partners, smoking and human immunodeficiency virus (HIV) have been described but never ranked in order of priority. We evaluated the contribution of several known lifestyle co-risk factors for cervical cancer among black South African women.

Methods: We used participant data from the Johannesburg Cancer Study, a case-control study of women recruited mainly at Charlotte Maxeke Johannesburg Academic Hospital between 1995 and 2016. A total of 3,450 women in the study had invasive cervical cancers, 95% of which were squamous cell carcinoma. Controls were 5,709 women with cancers unrelated to exposures of interest. Unconditional logistic regression models were used to calculate adjusted odds ratios (ORadj) and 95% confidence intervals (CI). We ranked these risk factors by their population attributable fractions (PAF), which take the local prevalence of exposure among the cases and risk into account.

Results: Cervical cancer in decreasing order of priority was associated with (1) being HIV positive (ORadj = 2.83, 95% CI = 2.53-3.14, PAF = 17.6%), (2) lower educational attainment (ORadj = 1.60, 95% CI = 1.44-1.77, PAF = 16.2%), (3) higher parity (3+ children vs 2-1 children (ORadj = 1.25, 95% CI = 1.07-1.46, PAF = 12.6%), (4) hormonal contraceptive use (ORadj = 1.48, 95% CI = 1.24-1.77, PAF = 8.9%), (5) heavy alcohol consumption (ORadj = 1.44, 95% CI = 1.15-1.81, PAF = 5.6%), (6) current smoking (ORadj = 1.64, 95% CI = 1.41-1.91, PAF = 5.1%), and (7) rural residence (ORadj = 1.60, 95% CI = 1.44-1.77, PAF = 4.4%). Conclunsion: This rank order of risks could be used to target educational messaging and appropriate interventions for cervical cancer prevention in South African women.


Effect of the Monthly Injectable Combined Contraceptives versus Oral  Contraceptive Pills on Mood

Ghada M Khafagy

Department of Family Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt.

Nagwa E Saad

Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt.

Hebatallah L Shalaby

Department of Family Medicine, Ministry of Health, Cairo, Egypt.

Abstract:
Background: Contraceptive agents are widely used by women of reproductive age, and resulting depression is the most common side effect of this usage. This study aimed to study the effect of monthly injectable combined contraceptives versus that of combined oral contraceptive pills (COC) on patients' mood.

Methods: A prospective cohort study was conducted on 124 females aged 18-45 years attending the Kom-Ashfeen Family Medicine Unit, El-Kalyubia, Egypt. Participants were divided into three groups according to their choice: group A included 44 participants who received monthly combined injectable contraceptives (CIC); group B included 40 participants who took COC; and group C included 40 participants who used the copper intrauterine device (IUD). The Patient Health Questionnaire-9 (PHQ-9) score was assessed at the beginning of the study and after 6 months of follow-up.

Results: After 6 months of follow-up, there were mild but statistically significant increases in the PHQ-9 score in groups A and B, with group A (CIC users) showing the highest increase. Approximately 34.1%, 27.5%, and 15% of CIC, COC, and IUD users, respectively, moved from the non-depression stage to mild depression after 6 months; this change was statistically significant in groups A and B only.

Conclusion: Monthly injectable combined contraceptives and oral contraceptive pills were associated with an increased risk of developing mild depression; this risk was higher in users of CICs, although the difference was not statistically significant. Thus, it is crucial to counsel patients about this possible risk and to follow them up. However, further studies are required to confirm our results.


A Scoping Review of Perinatal Palliative Care: Allowing Parents to Be Parents

Cara Buskmiller

Department of Obstetrics, Gynecology, and Women’s Health, St. Louis University, St. Louis, MO, USA

Abstract:
Objective: Perinatal palliative care (PPC) is an option for patients who discover that their infant has a life-limiting fetal condition, which decreases the burden of the condition using a multidisciplinary approach.

Study Design: This review discusses the landmark literature in the past two decades, which have seen significant growth and development in the concept of PPC.

Results: The literature describes the background, quality, and benefits of offering PPC, as well as the ethical principles that support its being offered in every discussion of fetal life-limiting diagnoses.

Conclusion: PPC shares a similar risk profile to other options after life-limiting diagnosis, including satisfaction with choice of continuation of pregnancy. The present clinical opinion closes by noting common barriers to establishing PPC programs and offers a response to overcome each one. KEY POINTS: · Perinatal palliative care serves patients who continue pregnancies with life-limiting fetal anomaly.. · Perinatal palliative care has a risk profile similar to other options such as termination.. · Health care providers can serve as champions to extend PPC to patients in their region..


Female Fertility and the Nutritional Approach: The Most Essential Aspects

Abstract: Infertility is an increasing problem that affects couples attempting pregnancy. A growing body of evidence points to a link between diet and female fertility. In fact, data show that a diet high in trans fats, refined carbohydrates, and added sugars can negatively affect fertility. Conversely, a diet based on the Mediterranean dietary patterns, i.e., rich in dietary fiber, omega-3 (ɷ-3) fatty acids, plant-based protein, and vitamins and minerals, has a positive impact on female fertility. An unhealthy diet can disrupt microbiota composition, and it is worth investigating whether the composition of the gut microbiota correlates with the frequency of infertility. There is a lack of evidence to exclude gluten from the diet of every woman trying to become pregnant in the absence of celiac disease. Furthermore, there are no data concerning adverse effects of alcohol on female fertility, and caffeine consumption in the recommended amounts also does not seem to affect fertility. On the other hand, phytoestrogens presumably have a positive influence on female fertility. Nevertheless, there are many unanswered questions with regard to supplementation in order to enhance fertility. It has been established that women of childbearing age should supplement folic acid. Moreover, most people experience vitamin D and iodine deficiency; thus, it is vital to control their blood concentrations and consider supplementation if necessary. Therefore, since diet and lifestyle seem to be significant factors influencing fertility, it is valid to expand knowledge in this area.


Nonhormonal therapy for endometriosis: a randomized, placebo-controlled, pilot study of cabergoline versus norethindrone acetate

Abstract:
OBJECTIVE: To estimate the efficacy and safety of a novel nonhormonal therapeutic agent, cabergoline, compared with that of the standard clinical therapy, norethindrone acetate (NETA), for the treatment of endometriosis-associated pain in young women with endometriosis.

DESIGN: Randomized, double-blind, placebo-controlled pilot study.

SETTING: Tertiary care center.

PATIENTS: Women (n = 9) with surgically confirmed endometriosis.

INTERVENTIONS: A random, double-blind assignment to either NETA (5 mg/day) + placebo twice weekly or cabergoline (0.5 mg) twice weekly + placebo daily for 6 months.

MAIN OUTCOME MEASURES: We collected the measures of pelvic pain and laboratory parameters every 3 months.

RESULTS: We observed a decrease in pain scores and increase in pain relief in women randomized to receive cabergoline, who appeared to show similar or more improvements than women treated with NETA. The serum measures of vascular endothelial growth factor receptor 1 declined over 6 months in those who received cabergoline. Cabergoline was well tolerated, and no serious adverse events occurred.

CONCLUSIONS: Safe, effective adjunct treatments are lacking for patients with endometriosis who do not respond to standard care. Because the growth of endometriosis requires angiogenesis, blood vessel growth is an attractive therapeutic target. This pilot study suggests that cabergoline, a vascular endothelial growth factor pathway inhibitor, is an effective therapeutic option for women with chronic pain due to endometriosis. Building upon this investigation, we will conduct larger, randomized trials of cabergoline, advancing research on the best treatments for endometriosis-particularly disease resistant to hormonal therapies.

CLINICAL TRIAL REGISTRATION NUMBER: clinicaltrials.gov; registration number NCT02542410.


Paracetamol use during pregnancy - a call for precautionary action

Abstract: Paracetamol (N-acetyl-p-aminophenol (APAP), otherwise known as acetaminophen) is the active ingredient in more than 600 medications used to relieve mild to moderate pain and reduce fever. APAP is widely used by pregnant women as governmental agencies, including the FDA and EMA, have long considered APAP appropriate for use during pregnancy when used as directed. However, increasing experimental and epidemiological research suggests that prenatal exposure to APAP might alter fetal development, which could increase the risks of some neurodevelopmental, reproductive and urogenital disorders. Here we summarize this evidence and call for precautionary action through a focused research effort and by increasing awareness among health professionals and pregnant women. APAP is an important medication and alternatives for treatment of high fever and severe pain are limited. We recommend that pregnant women should be cautioned at the beginning of pregnancy to: forego APAP unless its use is medically indicated; consult with a physician or pharmacist if they are uncertain whether use is indicated and before using on a long-term basis; and minimize exposure by using the lowest effective dose for the shortest possible time. We suggest specific actions to implement these recommendations. This Consensus Statement reflects our concerns and is currently supported by 91 scientists, clinicians and public health professionals from across the globe.


Uterine Isthmocele-A Frequently Overlooked Complication of Cesarean Sections

Abstract: Uterine isthmocele or uterine niche is a late complication of cesarean deliveries and causes chronic pelvic pain, menorrhagia or postmenstrual spotting, and infertility. As the number of cesarean sections are constantly increasing, it is important to be aware of this entity so as to make an early diagnosis. This would enable the clinicians to manage these patients efficiently. We present three patients of uterine isthmocele who were evaluated and managed at our institution.

The Indian Journal of Radiology & Imaging


Scar Tissue after a Cesarean Section—The Management of Different Complications in Pregnant Women

Abstract: The definition of a cesarean scar pregnancy (CSP) is the localization of the gestational sac (GS) in the cicatrix tissue, which is created in the front wall of the uterus after a previous cesarean section (CS). The worldwide prevalence of CSP has been growing rapidly. However, there are no general recommendations regarding prophylaxis and treatment of the abnormalities of the anterior wall of the uterus discovered in a non-pregnant myometrium, or how to deal with existing cases of CSP. We present the latest knowledge, a holistic approach to the biology, histology, imaging, and management concerning post-CS scars based on our cases, which were treated in the Department of Pregnancy and Pathology of Pregnancy in the Medical University of Lublin, Poland. In our study, we present images of tissue samples of areas with a cicatrix in the uterus, and ultrasound and MRI images of CSP. We discuss the advances in the biology of the post-CS scar tissue, the prevention techniques used to repair the scar defect (niche) before the pregnancy, and the treatment of different complications of CSP, such as the rupture of the gravid uterus or the dehiscence of the myometrium.

International Journal of Environmental Research and Public Health


Metabolic risk factors and fertility disorders: A narrative review of the female  perspective

Ronny Westerman

Federal Institute for Population Research

Abstract: Metabolic risk factors such as obesity are considered major obstacles to female fertility. Chronic infertility imposes psychological and social burdens on women because infertility violates societal gender roles. Although the prevalence of obesity among women is expected to increase in the future, the relevance of metabolic status for fertility is still underestimated. However, the assessment of metabolic risk factors is highly relevant for understanding fertility disorders and improving infertility treatment. This narrative review discusses the associations of metabolic risk factors (e.g. obesity, female athlete triad, oxidative stress) with significant infertility. An electronic search was conducted for studies published between 2006 and 2020 in Cumulative Index to Nursing and Allied Health Literature, ScienceDirect, PubMed, Scopus, Google Scholar and related databases. In total, this search identified 19,309 results for polycystic ovary syndrome, 28,969 results for endometriosis, and only 1611 results for idiopathic and/or unknown infertility. For the present narrative review, 50 relevant studies were included: 19 studies were on obesity, 24 studies investigated the female athlete triad, and seven studies addressed other risk factors, including reactive oxygen species. This narrative review confirms the direct impact of obesity on female infertility, while the effect of other risk factors needs to be confirmed by large-scale population studies.

Reproductive Biomedicine & Society Online


The Future of Fetal Surgery

The Future of Fetal Surgery

Abstract: The field of fetal medicine has evolved significantly over the past several decades. Our ability to identify and treat the unborn patient has been shaped by advancements in imaging technology, genetic diagnosis, an improved understanding of fetal physiology, and the development and optimization of in utero surgical techniques. The future of the field will be shaped by medical innovators pushing for the continued refinement of minimally invasive surgical technique, the application of pioneering technologies such as robotic surgery and in utero stem cell and gene therapies, and the development of innovative ex utero fetal support systems.

Obstetrics and Gynecology Clinics of North America


The relationship between hormonal contraception and cervical dysplasia/cancer controlling for human papillomavirus infection: A systematic review

Heidi E Jones

City University of New York (CUNY) Graduate School of Public Health and Health Policy, NY, United States; CUNY Institute for Implementation Science in Public Health, New York, NY, United States. El...

Katharine J McCarthy

City University of New York (CUNY) Graduate School of Public Health and Health Policy, NY, United States.

Janneke H H M van de Wijgert

Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Merseyside, United Kingdom.

Abstract:
ObjectiveS: tudies on the effect of long-term use of combined oral contraceptives (COCs) on cervical dysplasia and/or cancer risk have been inconsistent. Less is known about the effects of other forms of hormonal contraception (HC). We examine whether HC use increases the risk of incident cervical intraepithelial neoplasia (CIN) 2, 3 and/or cancer after accounting for preexisting human papillomavirus (HPV) infection.

Study design: Systematic review of prospective studies on HC use as risk factor for cervical dysplasia with HPV infection documented prior to outcome assessment including PubMed and EMBASE records between January 2000 and February 2020 (Prospero #CRD42019130725).

Results: Among nine eligible studies, seven described recency and type of HC use and therefore comprise the primary analysis; two studies limit comparisons to ever versus never use and are summarized separately. All seven studies explored the relationship between oral contraceptive (OC) use and cervical dysplasia/cancer incidence: two found increased risk (adjusted odds ratio, aOR = 1.5-2.7), one found no association but decreased risk when restricted to women with persistent HPV (adjusted hazard ratio = 0.5), and four found no association. None of the seven studies differentiated between COC and progestin-only pills (POPs) by use recency or duration. The only study that included injectable progestin-only contraception (DMPA) found increased CIN3 incidence among current versus never users (aOR = 1.6). The one study that included Norplant found no association. Two studies included intrauterine device (IUD) use, but did not differentiate between hormonal and copper IUDs, and found no association.

Conclusion: We found no consistent evidence that OC use is associated with increased risk for cervical dysplasia/cancer after controlling for HPV infection. There were too few studies of progestin-only injectables, implants or IUDs to assess their effect on cervical dysplasia/cancer risk.

Implications: Use of single self-reported HC measures and insufficient distinction by hormonal constituent cloud our understanding of whether some HCs increase risk for cervical cancer. Methodologically rigorous studies with distinct HCs measured as time-varying exposures are needed to inform cervical cancer prevention efforts and improve our understanding of cervical cancer etiology.


State of the Fertility Sector 2020/2021

State of the Fertility Sector 2020/2021

Human Fertilisation and Embryology Authority

Abstract:
# State of the fertility sector 2020/21
**Annual publication on HFEA licensed clinics**
Published: November 2021
[**Download the underlying dataset as .xlsx**](https://www.hfea.gov.uk/media/5czb4k2o/2024-02-26-state-of-the-sector-underlying-data.xlsx "State of the Sector 2020/21 underlying dataset").
## Table of contents
- [About this report](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2020-2021/#about-this-report)
- [HFEA regulatory response to COVID-19](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2020-2021/#hfea-regulatory-response-to-covid-19)
- [Maintaining regulatory oversight](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2020-2021/#maintaining-regulatory-oversight)
- [There were 77 inspections undertaken in 2020/21, taking a hybrid inspection approach](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2020-2021/#there-were-77-inspections-undertaken-in-2020-21-taking-a-hybrid-inspection-approach)
- [In 2020/21, 103 clinics were licensed by the HFEA to provide fertility treatment](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2020-2021/#in-2020-21-103-clinics-were-licensed-by-the-hfea-to-provide-fertility-treatment)
- [The number of incidents in 2020/21 is broadly consistent with previous years](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2020-2021/#the-number-of-incidents-in-2020-21-is-broadly-consistent-with-previous-years)
- [The number of severe incidents of OHSS reported declined in 2020/21](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2020-2021/#the-number-of-severe-incidents-of-ohss-reported-declined-in-2020-21)
- [A total of 88 patient complaints were received about licensed clinics in 2...


Fertility evaluation of infertile women: a committee opinion

Practice Committee of the American Society for Reproductive Medicine. Electronic address: asrm@asrm.org

Abstract: Diagnostic evaluation for infertility in women should be conducted in a systematic, expeditious, and cost-effective manner to identify all the relevant factors with an initial emphasis on the least invasive methods for detecting the most common causes of infertility. The purpose of this committee opinion is to provide a critical review of the current methods and procedures for the evaluation of in fertile women, and it replaces the document of the same name, last published in 2015 (Fertil Steril 2015;103:e44-50). This guidance is intended for any provider evaluating women for infertility.


Incidence, prevalence, and trends in endometriosis diagnosis: a United States population-based study from 2006 to 2015

Abstract:
BACKGROUND: Accurate estimates of incidence and prevalence of endometriosis among nonselected cohorts are lacking in the United States, and earlier reports have produced varying results.

OBJECTIVE: This study aimed to define endometriosis incidence and prevalence in a US population and evaluate factors influencing these estimates over time.

STUDY DESIGN: A 10-year retrospective cohort study using Kaiser Permanente Washington electronic health records database was completed. The primary analysis included women enrollees aged 16 to 60 years, from January 2006 to December 2015, who had a uterus, were continuously enrolled for at least 2 years before cohort entry and had at least 1 healthcare utilization. Secondary analysis included all women enrollees aged 16 to 60 years during this time. Incident endometriosis was identified using the International Classification of Diseases, Ninth Revision and Tenth Revision, diagnosis codes. Annual incidence rates were age-adjusted by direct standardization to the 2015 study population. Secular trends in incidence overall and by 5-year age group, race and ethnicity, diagnosis modality, and practitioner type were assessed using Poisson regression analyses. Prevalent cases were defined as women enrolled in 2015 and had an endometriosis diagnosis before the end of 2015. The prevalence rates of chronic pelvic pain and dysmenorrhea defined by the International Classification of Diseases, Ninth Revision and Tenth Revision, diagnosis codes in 2006-2015 were estimated.

RESULTS: Among 332,056 eligible women who contributed 1,176,329 person-years during the 10-year study period, 2863 incident endometriosis cases were identified for an average incidence of 24.3 cases per 10,000 person-years. In our primary analysis, incidence rates declined over the study interval from a high of 30.2 per 10,000 person-years in 2006 to 17.4 per 10,000 person-years in 2015 and were highest among women aged 36 to 45 years in most years. Incidence rates were similar across race and ethnicity groups. The distribution of the 2863 incident cases by the diagnosis modality was as follows: 45.5% surgical, 5.7% imaging, and 48.8% clinical. Endometriosis incidence rates per 10,000 person-years were similar in women who were surgically and clinically diagnosed and decreased significantly from 2006 to 2015 (surgically diagnosed endometriosis dropped from 13.4 to 7.4 and clinically diagnosed endometriosis dropped from 16.1 to 8.9; P value of <.001 for linear trend over time for each). Incident case distribution by diagnosing provider was as follows: 73.6% obstetrician and gynecologist, 15.7% primary care provider, and 10.7% "other." Incidence of endometriosis diagnosed by an obstetrician and gynecologist and primary care provider decreased over the study interval (P<.001 for linear trend over time for each). Method of diagnosis and provider type did not differ by race and ethnicity. Among 135,162 women who contributed person-time in 2015, 2521 women were diagnosed with endometriosis, a prevalence rate of 1.9%. In our secondary analysis, the frequency of chronic pelvic pain diagnosis increased over the study interval from 3.0% in 2006 to 5.6% in 2015.

CONCLUSION: The incidence rates of endometriosis declined over the 10-year study interval and did so uniformly across age groups, races and ethnicities, and the main diagnosing modalities and providers. Declining rates may reflect a shift in practice patterns in the United States away from the diagnosis of endometriosis both clinically and surgically, rather than favoring more general diagnoses of chronic pelvic pain. The prevalence of endometriosis in 2015 in the United States is in keeping with data from recent studies outside the United States using health record data.

American journal of obstetrics and gynecology


Testosterone Therapy in Women: A Clinical Challenge

Rebecca Dunsmoor-Su

University of Pennsylvania Health System

Abstract: The physiology of testosterone as a normal female hormone in reproductive years and beyond is poorly taught and understood. This has led to unregulated and dangerous prescribing practices by physicians and other health care professionals. There are data for safe use, and as women's health care practitioners, we owe it to our patients to follow these guidelines and practices, as well as advocate for more research and safer, regulated products to prescribe.


Deciphering mouse uterine receptivity for embryo implantation at single-cell resolution

Abstract:
OBJECTIVES: Mice are widely used as an animal model for studying human uterine receptivity for embryo implantation. Although transcriptional changes related to mouse uterine receptivity have been determined by using bulk RNA-seq, the data are of limited value because the uterus is a complex organ consisting of many cell types. Here, we aimed to decipher mouse uterine receptivity for embryo implantation at single-cell resolution.

MATERIALS AND METHODS: Single-cell RNA sequencing was performed for the pre-receptive and the receptive mouse uterus. Gene expression profiles in luminal epithelium and glandular epithelium were validated by comparing against a published laser capture microdissection (LCM)-coupled microarray dataset.

RESULTS: We revealed 19 distinct cell clusters, including 3 stromal cell clusters, 2 epithelial cell clusters, 1 smooth muscle cell cluster, 4 endothelial cell clusters and 8 immune cell clusters. We identified global gene expression changes associated with uterine receptivity in each cell type. Additionally, we predicted signalling interactions for distinct cell types to understand the crosstalk between the blastocyst and the receptive uterus.

CONCLUSION: Our data provide a valuable resource for deciphering the molecular mechanism underlying uterine receptivity in mice.


Quantitative versus qualitative estrogen and luteinizing hormone testing for  personal fertility monitoring

Abstract:
Background: A new fertility monitor is now available that provides quantitative measurement of urinary hormones, but clinical use requires validation against an established fertility monitor that provides only qualitative results. RESEARCH DESIGN AND

Methods: Two fertility monitors were compared using daily first morning urine samples over 3 cycles of use in 21 women users with experience using a fertility monitor with the Marquette Method of Natural Family Planning.

Results: Women were aged 33.4 ± 5.5 years and had menstrual cycles ranging between 23 and 41 days. The quantitative Mira Monitor estimates of ovulation were highly correlated with the qualitative ClearBlue Fertility Monitor (CBFM) estimates of ovulation. Both monitors provided an accurate estimate of the fertile window.

Conclusions: In this preliminary trial, the Mira monitor was shown to be effective at delineating the fertile window and ovulation. We demonstrated the feasibility of applying the Marquette Method algorithm with the use of the Mira monitor. Satisfaction differences between the two monitors did not reach statistical significance. We anticipate that quantitative fertility monitoring will give couples and health-care providers new and unprecedented insights into the menstrual cycle and fertility.


Near-Infrared Light and Skin: Why Intensity Matters

Abstract: Infrared light (760 nm-1 mm) constitutes approximately 40% of the solar radiation reaching the ground at sea level. Shortest wavelength near-infrared (NIR) photons (NIR or IR-A: 760-1,400 nm) can penetrate the epidermis, dermis, and subcutaneous tissue with numerous biological effects. NIR used to have a bad reputation on the basis of past studies using high-intensity artificial light sources (above the solar IR-A irradiance threshold) at high doses leading to detrimental effects (i.e., upregulation of matrix metalloproteinase-1). However, when looking at the other side of the coin and what we can learn from the sun, NIR intensity matters. Hence, mimicking sunlight NIR intensity (30-35 mW/cm2) will rather trigger beneficial cutaneous effects. It is likely that intensity is more important than the fluence (dose) delivered. Moreover, the law of reciprocity (i.e., the biological effect is directly proportional to the total dose irrespective of intensity) does not always apply when considering tissue response in photobiology. In fact, the biphasic dose curve (Arndt-Schulz curve) of photobiomodulation establishes that if irradiance is lower than the physiological threshold value for a given target, it does not produce beneficial effects, even when -irradiation duration is extended. Also, photo-inhibitory deleterious effects may occur at higher irradiances. Remarkably, the beneficial "sweet spot" in between corresponds to the irradiance of the sun. NIR might even precondition the skin from an evolutionary standpoint as exposure to early morning NIR wavelengths in sunlight may prepare the skin for upcoming mid-day harmful UVR. Consequently, NIR light appears to be the solution, not the problem.


Hiding in Plain Sight: Modern Thiamine Deficiency

Abstract: Thiamine or vitamin B1 is an essential, water-soluble vitamin required for mitochondrial energetics-the production of adenosine triphosphate (ATP). It is a critical and rate-limiting cofactor to multiple enzymes involved in this process, including those at the entry points and at critical junctures for the glucose, fatty acid, and amino acid pathways. It has a very short half-life, limited storage capacity, and is susceptible to degradation and depletion by a number of products that epitomize modern life, including environmental and pharmaceutical chemicals. The RDA for thiamine is 1.1-1.2 mg for adult females and males, respectively. With an average diet, even a poor one, it is not difficult to meet that daily requirement, and yet, measurable thiamine deficiency has been observed across multiple patient populations with incidence rates ranging from 20% to over 90% depending upon the study. This suggests that the RDA requirement may be insufficient to meet the demands of modern living. Inasmuch as thiamine deficiency syndromes pose great risk of chronic morbidity, and if left untreated, mortality, a more comprehensive understanding thiamine chemistry, relative to energy production, modern living, and disease, may prove useful.


Cyclic Progesterone Therapy in Androgenic Polycystic Ovary Syndrome (PCOS)-A  6-Month Pilot Study of a Single Woman's Experience Changes

Dharani Kalidasan

University of British Columbia, Vancouver, BC, Canada

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract:
Background and Objectives: Women with androgenic Polycystic Ovary Syndrome (PCOS) have increased endometrial cancer risk that cyclic progesterone will prevent; it may also reverse PCOS's neuroendocrine origins. This pilot study's purpose was to document 6-month experience changes in a woman with PCOS taking cyclic progesterone therapy because she was intolerant of combined hormonal contraceptive therapy, the current PCOS standard of care. A 31-year-old normal-weight woman with PCOS had heavy flow, irregular cycles, and was combined hormonal contraceptives-intolerant. She was prescribed cyclic oral micronized progesterone (OMP) (300 mg/h.s. cycle days 14-27). She kept Menstrual Cycle Diary© (Diary) records, starting with the 1st treatment cycle for six cycles; she was on no other therapy. Statistical analysis a priori hypothesized progesterone decreases high estradiol (E2) experiences (flow, cervical mucus, fluid retention, front-of-the-breast tenderness and anxiety); analysis focused on these. Our

objectives: (1) changes from cycles 1 to 6 in E2-related experiences; and (2) follicular phase E2-related changes from cycle 1 (no therapy) to cycles 3 and 6.

Materials and Methods: Data from consecutive Diaries were entered into an SPSS database and analyzed by Wilcoxon Signed Rank Test (Objective #1) within-person whole cycle ordinal data, and (Objective #2 follicular phase) repeated measures ANOVA.

Results: Cyclic OMP was associated with regular, shorter cycles (±SD) (28.2 ± 0.8 days). Comparison of cycles 1-6 showed decreased fluid retention (p = 0.001), breast tenderness (p = 0.002), and cervical mucus (p = 0.048); there were no changes in flow or anxiety. Fluid retention in the follicular phase also significantly decreased over time (F (1.2, 14.7) = 6.7, p = 0.017).

Conclusions: Pilot daily Diary data suggest women with PCOS have improved everyday experiences on cyclic progesterone therapy. Larger prospective studies with more objective outcomes and randomized controlled trials of this innovative PCOS therapy are needed.


Use of platelet-rich plasma in the treatment of infertility in poor responders in  assisted human reproduction procedures

Irina Pacu

Carol Davila University of Medicine and Pharmacy

Abstract: Couple infertility is a pathology with an absolute number of cases growing markedly over the last decade in connection mainly with the increased age of couples wishing to conceive. Platelet-rich plasma (PRP) is an alternative treatment used for several years for experimental purposes. Yet, this method is not yet defined as a standard therapeutic option in the infertility protocol for poor responders in assisted human reproduction procedures. Thus, the present study is a retrospective study conducted between February 2019 and February 2020 to evaluate the effect of ovarian PRP injection in patients with a poor ovarian response (POR) to ovarian stimulation. Women (n=20; age 31-44 years) diagnosed with POR based on the European Society of Human Reproduction and Embryology criteria underwent ovarian injection with autologous PRP injection. Markers of ovarian reserve before, during the following two menstrual cycles, and at six months after treatment were followed as well as stimulation and fertilisation parameters before and post-treatment. PRP treatment resulted in increased antral follicle count and serum anti-Mullerian hormone, while levels of serum follicle-stimulating hormone and luteinising hormone were decreased. These changes were more pronounced during the 2nd menstrual cycle following treatment. By six months following the injection, their values return to pre-treatment levels and any small differences were not considered statistically significant. The average dose of gonadotropin used and duration remained statistically unchanged, but a significant increase in estradiol achieved by the day of the human chorionic gonadotropin trigger day was achieved. The cancellation rate decreased following PRP treatment while the number of collected oocytes, number of oocytes in metaphase II rose. The number of embryos (of A and B quality) resulting also increased but fell short of the significance level set (α=0.073). Following the PRP injection, two singleton pregnancies were achieved, resulting in live births at term without complications during pregnancy. Another pregnancy was achieved spontaneously 45 months following the PRP and a failed assisted human reproduction procedure. Although the group included a small number of women, the results indicate the potential benefits of an ovarian autologous PRP injection in women with POR. Positive results appear to be short-term for 2-6 months after the procedure.


Where's the break? Critique of radiographic vertebral fracture diagnostic methods

Ling Oei

Departments of Internal Medicine and Epidemiology, Erasmus MC, Rotterdam, The Netherlands.

Fjorda Koromani

Department of EpidemiologyUniversity Medical Center RotterdamErasmus MCRotterdamThe Netherlands


Novel approaches to the management of recurrent pregnancy loss: The OPTIMUM  (OPtimization of Thyroid function, Thrombophilia, Immunity, and Uterine Milieu)  treatment strategy

Abstract:
Purpose: Does the OPtimization of Thyroid function, Thrombophilia, Immunity, and Uterine Milieu (OPTIMUM) treatment strategy, developed for treating repeated implantation failure (RIF), contribute to improving pregnancy outcomes in patients with a history of recurrent pregnancy loss (RPL)?

Methods: Between 2018 and 2019, women with RPL after two or more clinical pregnancy losses underwent RPL testing. We treated chronic endometritis with antibiotics, high Th1/Th2 cell ratios with vitamin D and/or tacrolimus, overt/subclinical hypothyroidism with levothyroxine, and thrombophilia with low-dose aspirin. Of 168 consecutive women aged ≤43 years, 115 underwent RPL testing. We compared 100 pregnancies (90 women) and 46 pregnancies (41 women) with and without the OPTIMUM treatment strategy, respectively.

Results: RPL testing identified intrauterine abnormalities in 66 (57.4%), elevated Th1/Th2 cell ratios in 50 (43.5%), thyroid dysfunction in 33 (28.7%), and thrombophilia in 33 (28.7%). The live birth rate in the OPTIMUM group was significantly higher than that in the control group among women aged <40 years (78.1% and 42.3%, respectively; p = 0.002), but no significant difference was observed in women aged ≥40 years (55.6% and 30.0%, respectively; p = 0.09).

Conclusions: The OPTIMUM treatment strategy improved pregnancy outcomes in patients with not only RIF but also RPL.


Investigating the potential of clinical and biochemical markers to differentiate between functional hypothalamic amenorrhoea and polycystic ovarian syndrome: A retrospective observational study

Roger Newman

Rutgers, The State University of New Jersey

Abstract:
OBJECTIVES: Functional hypothalamic amenorrhoea (FHA) is a common cause of amenorrhoea, but diagnosis can be challenging. The aim of this study was to investigate the clinical and biochemical features of FHA, compared to that of polycystic ovarian syndrome (PCOS) and assess the diagnostic performance of the different parameters for differentiating the two conditions.

DESIGN AND PATIENTS: This was a retrospective observational study. We analysed clinical and biochemical parameters of women diagnosed with FHA and PCOS following specialist assessment at the reproductive endocrine gynaecology clinic, St Mary's Hospital.

RESULTS: Compared with PCOS, women with FHA had significantly lower body mass index (BMI; 20.1 ± 2.9 vs. 31.1 ± 7.8 kg/m2 ; p< .0001) and a thinner endometrium (3.75 ± 2.23 vs. 6.82 ± 3.32 mm; p< .0001). Women with FHA had significantly lower luteinising hormone (LH; 3.46 ± 7.31 vs. 8.79 ± 4.98 IU/L; p< .0001), and lower LH to follicle-stimulating hormone (FSH) ratio, estradiol, thyroid-stimulating hormone, free thyroxine and prolactin levels; there was no significant difference in FSH levels. BMI had the greatest predictive performance for FHA (area under the curve [AUC]: 0.93; p< .001), followed by estradiol (AUC: 0.89; p< .001), LH (AUC: 0.88; p< .001) and LH:FSH ratio (AUC: 0.86; p< .001).

CONCLUSIONS: Our data provides quantification for diagnostic accuracy of clinical parameters to differentiate FHA from PCOS, namely low BMI, estradiol, LH and LH:FSH ratio. These data could help clinicians more reliably diagnose FHA in women with secondary amenorrhoea.


Hormonally Active Contraceptives, Part II: Sociological, Environmental, and  Economic Impact

Laura Haynes

International Federation for Therapeutic and Counseling Choice, General Board Member and USA Country Representative,Tustin, California, USA

Abstract:
To investigate the sociological, environmental, and economic impact of hormonally active contraceptives, a series of comprehensive literature surveys were employed. Sociological effects are discussed including abortion, exploitation of women, a weakening of marriage, and an increase in divorce with deleterious effects on children such as child poverty, poorer health, lower educational achievement, suicide risks, drug and alcohol abuse, criminality, and incarceration, among others. The environmental impact is discussed briefly and includes the feminization and trans-gendering of male fish downstream from the effluent of city wastewater treatment plants with declining fish populations. The potential economic impact of most of these side effects is estimated based on epidemiologic data and published estimates of costs of caring for the diseases which are linked to the use of hormonally active contraceptives. Hormonally active contraceptives appear to have a deleterious impact on multiple aspects of women's health as well as negative economic and environmental impacts. These risks can be avoided through the use of nonhormonal methods and need to be more clearly conveyed to the public.
Summary: Hormonal contraceptives have wide-ranging effects. The potential economic impact of the medical side effects is estimated. Sociological effects are discussed including abortion, exploitation of women, a weakening of marriage and an increase in divorce with negative effects on children such as child poverty, poorer health, lower educational achievement, suicide risks, drug and alcohol abuse, criminality and incarceration among others. The environmental impact includes hormonal effects on fish with declining fish populations. Women seeking birth control have a right to know about how to avoid these risks by using effective hormone-free methods like Fertility Awareness Methods.


Benefits of α-lipoic acid in high-risk pregnancies (Review)

Abstract: α-Lipoic acid (ALA) is a natural molecule that is inconsistently synthesized by the human body and must be provided from exogenous sources, such as food and dietary supplements. Once absorbed, the oxidized form of ALA is transformed into its reduced form, dihydrolipoic acid (DHLA). ALA/DHLA exert direct and indirect antioxidant, anti-inflammatory and fine immunomodulatory effects. ALA/DHLA reduce the levels of pro-inflammatory cytokines (IL-1β, IL-6, IL-8 and IL-17), while increasing the secretion of anti-inflammatory cytokines (IL-10). They also inhibit cyclooxygenase 2, thereby decreasing the secretion of prostaglandin E2 and nitrogen oxide, and reducing the risk of miscarriage in the first trimester of pregnancy. In patients at risk of abortion, administration of ALA from the first trimester has shown efficacy by accelerating subchorionic hematoma resorption, with a significant decrease in the accompanying abdominal pain. ALA has been proven to be efficient in maintaining the length of the cervix and keeping it closed following one episode of premature labor. Preeclampsia is a dysfunction caused by abnormal placentation and an excessive maternal inflammatory response, leading to extreme hypoxia in the placental bed and exaggerated oxidative stress, with release of oxygen free radicals. Oxidative stress plays a key role in the development of preeclampsia and intrauterine growth restriction. The hypothesis of antioxidant supplementation may play an essential part in disease prevention and fetal neuroprotection.


Time to Pregnancy for Women Using a Fertility Awareness Based Mobile Application  to Plan a Pregnancy

Simon P Rowland

Natural Cycles USA Corp, New York, New York, USA.

Anne Marie Z. Jukic

National Institute of Environmental Health Sciences

Elina Berglund Scherwitzl

Natural Cycles Nordic AB, Stockholm, Sweden

Kristina Gemzell-Danielsson

Department of Women's and Children's Health, Karolinska institutet, SE-17177 Stockholm, Sweden.

Abstract:
Background: Time to pregnancy (TTP) is a biomarker of fecundability and has been associated with behavioral and environmental characteristics; however, these associations have not been examined in a large population-based sample of application (app) users.

Materials and Methods: This observational study followed 5,376 women with an age range of 18 to 45 years who used an app to identify their fertile window. We included women who started trying to conceive between September 30, 2017 and August 31, 2018. TTP was calculated as the number of menstrual cycles from when the user switched to "Plan" mode up to and including the cycle in which they logged a positive pregnancy test. We examined associations with several characteristics, including age, gravidity, body mass index, cycle length and cycle length variation, frequency of sexual intercourse, and temperature measuring frequency. Discrete time fecundability models were used to estimate fecundability odds ratios.

Results: For the complete cohort the 6-cycle and 12-cycle cumulative pregnancy probabilities were found to be 61% (95% confidence interval [CI]: 59-62) and 74% (95% CI: 73-76), respectively. The median TTP was four cycles. The highest fecundability was associated with an age of less than 35 years, with cycle length variation <5 days and logging sexual intercourse on at least 20% of days added (the proportion of days in which intercourse was logged) (11.5% [n = 613] of entire sample). This group achieved a 6and 12-cycle cumulative pregnancy probability of 88% (95% CI: 85-91) and 95% (95% CI: 94-97), respectively, and a TTP of 2 cycles.

Conclusions: Natural Cycles was an effective method of identifying the fertile window and a noninvasive educational option for women planning a pregnancy. Women under age 35 with regular cycles showed a high pregnancy rate.


Cyclic progesterone and spironolactone treatment for androgenic polycystic ovary syndrome

Dharani Kalidasan

University of British Columbia, Vancouver, BC, Canada

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre


The Function of Cumulus Cells in Oocyte Growth and Maturation and in Subsequent Ovulation and Fertilization

Abstract: Cumulus cells (CCs) originating from undifferentiated granulosa cells (GCs) differentiate in mural granulosa cells (MGCs) and CCs during antrum formation in the follicle by the distribution of location. CCs are supporting cells of the oocyte that protect the oocyte from the microenvironment, which helps oocyte growth and maturation in the follicles. Bi-directional communications between an oocyte and CCs are necessary for the oocyte for the acquisition of maturation and early embryonic developmental competence following fertilization. Follicle-stimulation hormone (FSH) and luteinizing hormone (LH) surges lead to the synthesis of an extracellular matrix in CCs, and CCs undergo expansion to assist meiotic resumption of the oocyte. The function of CCs is involved in the completion of oocyte meiotic maturation and ovulation, fertilization, and subsequent early embryo development. Therefore, understanding the function of CCs during follicular development may be helpful for predicting oocyte quality and subsequent embryonic development competence, as well as pregnancy outcomes in the field of reproductive medicine and assisted reproductive technology (ART) for infertility treatment.


IDENTIFYING ANATOMICAL REGIONS ASSOCIATED WITH ENDOMETRIOSIS PAIN USING NEIGHBOR-JOINING CLUSTERING