Cytokines and immuno-endocrine factors in recurrent miscarriage

Comparison of the prevalence of chronic endometritis as determined by means of different diagnostic methods in women with and without reproductive failure

Liu Y et al., 2018 · Fertility and sterility

To compare the prevalence of chronic endometritis (CE) when different diagnostic methods are used. Prospective observational study. University-affiliated hospital. PATIENT(S): Four groups of women were studied, including women with proven fertility (Fertile; n = 40), unexplained recurrent miscarriage (RM; n = 93), recurrent implantation failure (RIF; n = 39), and infertile subjects undergoing endometrial scratch in a natural cycle preceding frozen-thawed embryo transfer (Infertility; n = 48). INTERVENTION(S): Endometrial biopsy was performed precisely 7 days after LH surge (LH+7). Plasma cells were identified by means of traditional hematoxylin and eosin (HE) staining and by means of immunohistochemistry (IHC) for Syndecan-1 (CD138). MAIN OUTCOME MEASURE(S): Prevalence of CE. RESULT(S): The use of CD138 epitope was more sensitive than HE staining in identifying plasma cells. The use of plasma cell count per unit area had the lowest observer variability compared with cell count per ten randomly chosen high-power fields and cell count per section. Using this method, the prevalence of CE in women with RM, RIF, and Infertility were 10.8%, 7.7%, and 10.4%, respectively, not significantly higher than that of Fertile subjects (5.0%). CONCLUSION(S): Using what may be a new method of plasma cell assessment, it appears that the prevalence rates of CE reported in many earlier studies may have been overestimated. CLINICAL ChiCTR-IOC-16007882.

The International Glossary on Infertility and Fertility Care, 2017

Zegers-Hochschild F et al., 2017 · Hum Reprod · Free full text on PubMed Central

Can a consensus and evidence-driven set of terms and definitions be generated to be used globally in order to ensure consistency when reporting on infertility issues and fertility care interventions, as well as to harmonize communication among the medical and scientific communities, policy-makers, and lay public including individuals and couples experiencing fertility problems? A set of 283 consensus-based and evidence-driven terminologies used in infertility and fertility care has been generated through an inclusive consensus-based process with multiple stakeholders. In 2006 the International Committee for Monitoring Assisted Reproductive Technologies (ICMART) published a first glossary of 53 terms and definitions. In 2009 ICMART together with WHO published a revised version expanded to 87 terms, which defined infertility as a disease of the reproductive system, and increased standardization of fertility treatment terminology. Since 2009, limitations were identified in several areas and enhancements were suggested for the glossary, especially concerning male factor, demography, epidemiology and public health issues. STUDY DESIGN, SIZE, Twenty-five professionals, from all parts of the world and representing their expertise in a variety of sub-specialties, were organized into five working groups: clinical definitions; outcome measurements; embryology laboratory; clinical and laboratory andrology; and epidemiology and public health. Assessment for revisions, as well as expansion on topics not covered by the previous glossary, were undertaken. A larger group of independent experts and representatives from collaborating organizations further discussed and assisted in refining all terms and definitions. PARTICIPANTS/MATERIALS, SETTING, Members of the working groups and glossary co-ordinators interacted through electronic mail and face-to-face in international/regional conferences. Two formal meetings were held in Geneva, Switzerland, with a final consensus meeting including independent experts as well as observers and representatives of international/regional scientific and patient organizations. MAIN A consensus-based and evidence-driven set of 283 terminologies used in infertility and fertility care was generated to harmonize communication among health professionals and scientists as well as the lay public, patients and policy makers. Definitions such as 'fertility care' and 'fertility awareness' together with terminologies used in embryology and andrology have been introduced in the glossary for the first time. Furthermore, the definition of 'infertility' has been expanded in order to cover a wider spectrum of conditions affecting the capacity of individuals and couples to reproduce. The definition of infertility remains as a disease characterized by the failure to establish a clinical pregnancy; however, it also acknowledges that the failure to become pregnant does not always result from a disease, and therefore introduces the concept of an impairment of function which can lead to a disability. Additionally, subfertility is now redundant, being replaced by the term infertility so as to standardize the definition and avoid confusion. LIMITATIONS, All stakeholders agreed to the vast majority of terminologies included in this glossary. In cases where disagreements were not resolved, the final decision was reached after a vote, defined before the meeting as consensus if passed with 75%. Over the following months, an external expert group, which included representatives from non-governmental organizations, reviewed and provided final feedback on the glossary. Some terminologies have different definitions, depending on the area of medicine, for example demographic or clinical as well as geographic differences. These differences were taken into account and this glossary represents a multinational effort to harmonize terminologies that should be used worldwide. None. N/A.

A Randomized Trial of Progesterone in Women with Recurrent Miscarriages

Coomarasamy A et al., 2015 · N Engl J Med

Progesterone is essential for the maintenance of pregnancy. However, whether progesterone supplementation in the first trimester of pregnancy would increase the rate of live births among women with a history of unexplained recurrent miscarriages is uncertain. We conducted a multicenter, double-blind, placebo-controlled, randomized trial to investigate whether treatment with progesterone would increase the rates of live births and newborn survival among women with unexplained recurrent miscarriage. We randomly assigned women with recurrent miscarriages to receive twice-daily vaginal suppositories containing either 400 mg of micronized progesterone or matched placebo from a time soon after a positive urinary pregnancy test (and no later than 6 weeks of gestation) through 12 weeks of gestation. The primary outcome was live birth after 24 weeks of gestation. A total of 1568 women were assessed for eligibility, and 836 of these women who conceived naturally within 1 year and remained willing to participate in the trial were randomly assigned to receive either progesterone (404 women) or placebo (432 women). The follow-up rate for the primary outcome was 98.8% (826 of 836 women). In an intention-to-treat analysis, the rate of live births was 65.8% (262 of 398 women) in the progesterone group and 63.3% (271 of 428 women) in the placebo group (relative rate, 1.04; 95% confidence interval [CI], 0.94 to 1.15; rate difference, 2.5 percentage points; 95% CI, -4.0 to 9.0). There were no significant between-group differences in the rate of adverse events. Progesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with a history of unexplained recurrent miscarriages. (Funded by the United Kingdom National Institute of Health Research; PROMISE Current Controlled Trials number, ISRCTN92644181.).

How precise is histologic dating of endometrium using the standard dating criteria?

Li TC et al., 1989 · Fertil Steril

Sixty-three endometrial biopsies were dated histologically by using the standard criteria on two separate occasions by the same observer. Overall, it was found that exact agreement occurred in 15 (24%), but disagreement of more than 2 days occurred in 6 (10%). The proportion of exact agreement in the first half of the luteal phase (32%) was found to be significantly higher (P less than 0.05) than that in the second half of the luteal phase (9%). In a separate part of the study, 27 women had two endometrial biopsies, each performed in a separate cycle. The within-subject between-cycle variation of the results of endometrial dating (exact agreement: 4%, disagreement of more than 2 days: 41%) was found to be significantly different from intraobserver variation (P less than 0.01 for both). The amount of intraobserver variation suggests that the traditional dating criteria are not precise enough to quantify corpus luteum function in the second half of the luteal phase, whereas the amount of within-subject between-cycle variation implies that the result of endometrial dating in one cycle cannot be used reliably to predict that of another cycle.

Chapter 57: Recurrent Spontaneous Abortion

Hilgers TW, 2004 · The Medical and Surgical Practice of NaProTECHNOLOGY

Recurrent spontaneous abortion is examined through a systematic NaProTECHNOLOGY diagnostic framework that includes hormonal, anatomical, immunological, and infectious etiologies identified via CrMS cycle charting and targeted laboratory evaluation. Correcting underlying pathology—particularly luteal phase deficiency and uterine structural abnormalities—achieves live birth rates substantially higher than expectant management alone.

The role of lymphocytes in fetal development and recurrent pregnancy loss

Modzelewski J et al., 2019 · Ginekol Pol · Free to read

Fetal survival and development is supported by the maternal immune system. Questions regarding those mechanisms have risen from development of transplantation medicine and observation of graft rejection. Initial theories of anatomic division, fetal immune immaturity and maternal immune system inertia were found incorrect. Rejection of fetal "semi-allograft" by maternal immune system could result in pregnancy loss. Two pregnancy losses of any etiology are considered recurrent and effort should be made to name the probable cause. Immune causes of pregnancy loss are probably multifactorial, thus difficult to research and implement findings in clinical practice. Although a full understating of pregnancy loss is not established, new therapies are being developed. This review summarizes the role of lymphocytes in pregnancy development, presents data from studies on recurrent pregnancy loss patients, evidence of new therapies and ESHRE guidelines regarding immunologic investigations.

Etiologic Factors in Women with a History of Recurrent Pregnancy Loss

Kutteh W H et al., 1999 · Obstetrics & Gynecology

Exploring the Immunological Aspects and Treatments of Recurrent Pregnancy Loss and Recurrent Implantation Failure

Garmendia JV et al., 2025 · International journal of molecular sciences · Free full text on PubMed Central

Recurrent pregnancy loss (RPL) is defined as the occurrence of two or more consecutive pregnancy losses before 24 weeks of gestation. It affects 3-5% of women who are attempting to conceive. RPL can stem from a variety of causes and is frequently associated with psychological distress and a diminished quality of life. By contrast, recurrent implantation failure (RIF) refers to the inability to achieve a successful pregnancy after three or more high-quality embryo transfers or at least two instances of egg donation. RIF shares several causative factors with RPL. The immunological underpinnings of these conditions involve alterations in uterine NK cells, reductions in M2 macrophages and myeloid-derived suppressor cells, an increased Th1/Th2 ratio, a decreased Treg/Th17 ratio, the presence of shared ≥3 HLA alleles between partners, and autoimmune disorders. Various therapeutic approaches have been employed to address these immunological concerns, achieving varying degrees of success, although some therapies remain contentious within the medical community. This review intends to explore the immunological factors implicated in RPL and RIF and to analyze the immunological treatments employed for these conditions, which may include steroids, intravenous immunoglobulins, calcineurin inhibitors, anti-TNF antibodies, intralipid infusions, granulocyte colony-stimulating factor, and lymphocyte immunotherapy.