• Endometrial hyperplasia can be classified as either hyperplasia without atypia or atypical hyperplasia. • Abnormal uterine bleeding is the most common symptom of endometrial hyperplasia. Transvaginal ultrasound is recommended for initial imaging to evaluate endometrial hyperplasia (evidence level 2+), while transrectal ultrasound is recommended for virgo patients (evidence level 3). • Endometrial biopsy should be used to confirm diagnosis in patients where endometrial lesions are suspected. Effective histological approaches to make definite diagnoses include diagnostic curettage (evidence level 2++), hysteroscopic-guided biopsy (evidence level 2+) and endometrial aspiration biopsy (evidence level 2-). • Progesterone is the preferred medication for the treatment of endometrial hyperplasia without atypia. Compared to oral progestins, placement of a levonorgestrel-releasing intrauterine system (LNG-IUS) has been associated with higher regression rates, lower recurrence rates and fewer adverse events which can be the initial treatment method. (Meta evidence level 1-, RCT evidence level 2+). Ultrasound and endometrial biopsies should be performed every 6 months during treatment to evaluate its effect and treatment should continue until no pathological changes are observed in two consecutive endometrial biopsies. Hysterectomy is not the preferred choice of treatment for patients with endometrial hyperplasia without atypia. • Minimally invasive hysterectomy is indicated for patients with endometrial atypical hyperplasia (evidence level 1+), bilateral fallopian tubes should also be removed (evidence level 2+). In cases where surgery cannot be tolerated, fertility is desired or the patient is younger than 45 years old, medical therapy is recommended (evidence level 3). LNG-IUS is the preferred medical therapy method (evidence level 2+). Endometrial pathologic evaluation should be performed every 3 months during conservative treatments, with adjustments made to dosages or approaches based on observed response to medication. Treatment should continue until no pathological changes are detected in two consecutive endometrial biopsies (evidence level 2++). There is no indication of sentinel lymph nodes biopsy and/or lymphadenectomy for hyperplasia with or without atypia. • Total hysterectomy is recommended to treat patients with recurrent endometrial atypical hyperplasia (evidence level 3); however, medical conservative therapy may be considered for patients hoping to become pregnant in the future. • Patients with fully regressed disease who would like to become pregnant should be advised to seek assistance through assisted reproductive technologies (evidence level 3). • Long-term follow-up is suggested for patients after endometrial hyperplasia treatment (evidence level 2+). Patient education is imperative for improving medication adherence, increasing regression rates and lowering recurrence rates (evidence level 3).

In this guideline, recurrent miscarriage has been defined as three or more first trimester miscarriages. However, clinicians are encouraged to use their clinical discretion to recommend extensive evaluation after two first trimester miscarriages, if there is a suspicion that the miscarriages are of pathological and not of sporadic nature. Women with recurrent miscarriage should be offered testing for acquired thrombophilia, particularly for lupus anticoagulant and anticardiolipin antibodies, prior to pregnancy. [Grade C] Women with second trimester miscarriage may be offered testing for Factor V Leiden, prothrombin gene mutation and protein S deficiency, ideally within a research context. [Grade C] Inherited thrombophilias have a weak association with recurrent miscarriage. Routine testing for protein C, antithrombin deficiency and methylenetetrahydrofolate reductase mutation is not recommended. [Grade C] Cytogenetic analysis should be offered on pregnancy tissue of the third and subsequent miscarriage(s) and in any second trimester miscarriage. [Grade D] Parental peripheral blood karyotyping should be offered for couples in whom testing of pregnancy tissue reports an unbalanced structural chromosomal abnormality [Grade D] or there is unsuccessful or no pregnancy tissue available for testing. [GPP] Women with recurrent miscarriage should be offered assessment for congenital uterine anomalies, ideally with 3D ultrasound. [Grade B] Women with recurrent miscarriage should be offered thyroid function tests and assessment for thyroid peroxidase (TPO) antibodies. [Grade C] Women with recurrent miscarriage should not be routinely offered immunological screening (such as HLA, cytokine and natural killer cell tests), infection screening or sperm DNA testing outside a research context. [Grade C] Women with recurrent miscarriage should be advised to maintain a BMI between 19 and 25 kg/m2 , smoking cessation, limit alcohol consumption and limit caffeine to less than 200 mg/day. [Grade D] For women diagnosed with antiphospholipid syndrome, aspirin and heparin should be offered from a positive test until at least 34 weeks of gestation, following discussion of potential benefits versus risks. [Grade B] Aspirin and/or heparin should not be given to women with unexplained recurrent miscarriage. [Grade B] There are currently insufficient data to support the routine use of PGT-A for couples with unexplained recurrent miscarriage, while the treatment may carry a significant cost and potential risk. [Grade C] Resection of a uterine septum should be considered for women with recurrent first or second trimester miscarriage, ideally within an appropriate audit or research context. [Grade C] Thyroxine supplementation is not routinely recommended for euthyroid women with TPO who have a history of miscarriage. [Grade A] Progestogen supplementation should be considered in women with recurrent miscarriage who present with bleeding in early pregnancy (for example 400 mg micronised vaginal progesterone twice daily at the time of bleeding until 16 weeks of gestation). [Grade B] Women with unexplained recurrent miscarriage should be offered supportive care, ideally in the setting of a dedicated recurrent miscarriage clinic. [Grade C].

In November 2021, NICE updated its clinical guideline that covers the management of threatened miscarriage in the first trimester. They recommended offering vaginal micronised progesterone twice daily until 16 completed weeks of pregnancy in those with a previous miscarriage. However, the duration of treatment is not evidence based. In the major clinical trial that informed the guideline, there was no benefit in starting progesterone after 9 weeks and the full effect of progesterone was present at 12 weeks of pregnancy. There are theoretical risks impacting offspring health in later life after maternal pharmaceutical progesterone treatment. As the effect of progesterone seems to be complete by 12 weeks of gestation, we should consider carefully whether to follow the guidance and treat up to 16 weeks of pregnancy.
In November 2021, new guidelines were published about the management of bleeding in early pregnancy. If someone who has had a previous miscarriage starts bleeding, they should now be treated with progesterone as this slightly reduces the chance of miscarriage. The guideline says progesterone should be given if the pregnancy is in the womb, and potentially normal, until 16 weeks of pregnancy. However, in the big studies looking at progesterone\'s effect in reducing miscarriage the beneficial effects of progesterone were complete by 12 weeks of pregnancy. At that stage, it is the placenta and not the mother\'s ovary that makes the progesterone to support the pregnancy. We do not know the long-term effects of giving extra progesterone during pregnancy on the offspring. Some research has raised the possibility that there might be some adverse effects if progesterone is given for too long. Maybe the guidance should have suggested stopping at 12 weeks rather than 16 weeks of pregnancy.

OBJECTIVE: The aim of this study was to investigate guidelines on preterm birth, analyze decision-criteria, and to identify consensus and discrepancies among these guidelines.
METHODS: Objective consensus analysis of guidelines.
METHODS: Ten international guidelines on preterm birth.
METHODS: Relevant decision criteria were singleton vs. twin pregnancy, history, cervical length, and cervical surgery / trauma or Mullerian anomaly. Eight treatment recommendations were extracted. For each decision-making criteria the most commonly recommended treatment was identified, and the level of consensus was evaluated.
METHODS: Consensus and Discrepancies among recommendations.
RESULTS: In a case of singleton pregnancies with no history of preterm birth and shortened cervix, most guidelines recommend progesterone. In singleton pregnancies with a positive history and shortened cervix, all guidelines recommend a cerclage as an option, alternative or conjunct to progesterone. The majority of the guidelines advise against treatment in twin pregnancies.
CONCLUSIONS: A shortened cervix and a history of preterm birth are relevant in singleton pregnancies. In twins, most guidelines recommend no active treatment. Among international guidelines a shortened cervix and a history of preterm birth are relevant in singleton pregnancies. With no history of preterm birth and with a shortened cervix most guidelines recommend progesterone treatment.

UNASSIGNED: The concentration of serum progesterone is commonly used to determine the optimal mating time in bitches, and to diagnose reproductive-related abnormalities. This study aims to compare the serum progesterone results obtained by rapid fluorescence immunochromatography assay (RFICA) with those obtained by chemiluminescent microparticle immunoassay (CMIA) from the same serum samples to develop a standard guideline for optimal breeding time.
UNASSIGNED: Serum progesterone levels were measured in 124 bitches using RFICA and CMIA. Simple linear regression and correlation analyses were performed to analyze the data. The percentage difference between the maximum and minimum progesterone values in the same serum sample in the same assay was compared using Wilcoxon\'s rank-sum test.
UNASSIGNED: The present study showed a strong linear dependence of the results obtained by RFICA on those obtained by CMIA as R2=0.8976, with regression coefficient of 0.9474 and p<0.05, including the regression model was CMIA = (0.9483 × RFICA) - 0.761. Moreover, five critical measurement times during estrous in bitches showed statistically significant differences (p<0.05), except at the fertilizable period, which showed a non-significant difference (p>0.05).
UNASSIGNED: This study demonstrated that it is presumably acceptable to use the RFICA and CMIA methods interchangeably for quality progesterone measurements in serum samples from bitches. However, when considering the use of the RFICA method, it is advisable to carefully interpret the results and follow the interpretation guidelines. Finally, RFICA in the present study provides a reliable and convenient option for veterinarian practitioners to measure canine progesterone levels in-house.

Menopause Hormonal Treatment (MHT) was initially developed to correct the climacteric symptoms induced by postmenopausal estrogen deficiency. In non-hysterectomized women, MHT combines estrogens and a progestogen, the latter opposing the negative impact of estrogen on endometrial proliferation. In France, and contrary to the USA and Northern European countries, MHT mainly combines 17β-estradiol, which is the physiological estrogen produced by the ovary, and progesterone or its derivative, dihydrogesterone. France has been a pioneer in the development of cutaneous administration routes (gel or transdermal patch) for estradiol, allowing better metabolic tolerance and a reduction of the risk of venous thromboembolism compared to the oral route. The choice of the doses as well as the treatment regimen is underpinned by tolerance as well as acceptance and compliance. The risk of breast cancer, which is one of the main risks of MHT, is higher with estro-progestogen combinations than with estrogens alone ; the preferential use of progesterone or dihydrogesterone being likely to limit the excess risk of breast cancer associated with MHT at least for duration of treatment of less than 5 to 7 years. The question of the optimal duration of MHT remains an issue and must take into account the initial indication of treatment as well as the benefit-risk balance, which is specific to each woman. Continuation of MHT is conditioned by the benefit-risk balance, which must be evaluated regularly, but also by the evolution of symptoms when MHT is stopped as well as menopause-related health risks or induced by MHT. After stopping MHT, it is necessary to maintain a medical follow-up to be adapted to the clinical situation of each woman and in particular, her cardiovascular and gynecological risk factors.

BACKGROUND: Verification of new reagent lots is a part of the crucial tasks in clinical laboratories. The Clinical and Laboratory Standards Institute (CLSI) EP26-A guideline provides laboratories with an evaluation method for reagent verification. The purpose of this study was to compare the performance of EP26-A with our laboratory reagent lot verification protocol and get the final scheme.
METHODS: 16 chemiluminescence analytes including estradiol (E2), progesterone (P), ferritin (FER), cortisol (COR),carbohydrate antigen 153 (CA153), and free prostate-specific antigen (FPSA). were prospectively evaluated in two reagent lots. The laboratory\'s lot verification process included evaluating 5 patient samples with the current and new lots and acceptability according to a predefined criteria. For EP26-A, method imprecision data and critical differences at medical decision points were important factors affecting the sample size requirements and rejection limits.
RESULTS: The number of samples required for EP26-A was 3 to 12, of which P, CA153, and FPSA had increased by more than 5 samples compared with the current protocol. Of the 16 chemiluminescence analytes, 11 had higher rejection limits when using EP26-A than the current laboratory scheme. Our current protocol and EP26-A were in agreement in 32 of the 32 (100%) paired verifications.
CONCLUSIONS: The EP26-A protocol is an important tool to find the differences between reagent lots, and it makes up for the loopholes in the statistical efficiency, sample concentration and quantity, and the selection of rejection limits in the current protocol.

Breast cancer risk from pesticides may be missed if effects on mammary gland are not assessed in toxicology studies required for registration. Using US EPA\'s registration documents, we identified pesticides that cause mammary tumors or alter development, and evaluated how those findings were considered in risk assessment. Of 28 pesticides that produced mammary tumors, EPA\'s risk assessment acknowledges those tumors for nine and dismisses the remaining cases. For five pesticides that alter mammary gland development, the implications for lactation and cancer risk are not assessed. Many of the mammary-active pesticides activate pathways related to endocrine disruption: altering steroid synthesis in H295R cells, activating nuclear receptors, or affecting xenobiotic metabolizing enzymes. Clearer guidelines based on breast cancer biology would strengthen assessment of mammary gland effects, including sensitive histology and hormone measures. Potential cancer risks from several common pesticides should be re-evaluated, including: malathion, triclopyr, atrazine, propylene oxide, and 3-iodo-2-propynyl butylcarbamate (IPBC).

To assess the benefits and risks of progesterone therapy for women at increased risk of spontaneous preterm birth (SPB) and to make recommendations for the use of progesterone to reduce the risk of SPB and improve postnatal outcomes.
To administer or withhold progesterone therapy for women deemed to be at high risk of SPB.
Preterm birth, neonatal morbidity and mortality, and postnatal outcomes including neurodevelopmental outcomes.
Maternity care providers, including midwives, family physicians, and obstetricians.
Pregnant women at increased risk of SPB.
Medline, PubMed, EMBASE, and the Cochrane Library were searched from inception to October 2018 for medical subject heading (MeSH) terms and keywords related to pregnancy, preterm birth, previous preterm birth, short cervix, uterine anomalies, cervical conization, neonatal morbidity and mortality, and postnatal outcomes. This document represents an abstraction of the evidence rather than a methodological review.
This guideline was reviewed by the Maternal-Fetal Medicine Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) and approved by the SOGC Board of Directors.
Therapy with progesterone significantly reduces the risk of SPB in a subpopulation of women at increased risk. Although this therapy entails a cost to the woman in addition to the discomfort associated with its use, no other adverse effects to the mother or the baby have been identified.
RECOMMENDATIONS (GRADE RATINGS IN PARENTHESES).

In France, 60,000 neonates are born preterm every year (7.4%), half of them after the spontaneous onset of labor. Among preventable risk factors of spontaneous prematurity, only cessation of smoking is associated with decreased prematurity (level of evidence [LE]1). It is therefore recommended (Grade A). Routine screening and treatment of vaginal bacteriosis is not recommended in the general population (Grade A). The only population for which vaginal progesterone is recommended is that comprising asymptomatic women with singleton pregnancies, no history of preterm delivery, and a short cervix at 16-24 weeks of gestation (Grade B). A history-indicated cerclage is not recommended for women with only a history of conization (Grade C), uterine malformation (professional consensus), isolated history of preterm delivery (Grade B), or twin pregnancies for primary (Grade B) or secondary (Grade C) prevention of preterm birth. A history-indicated cerclage is recommended for a singleton pregnancy with a history of at least 3 late miscarriages or preterm deliveries (Grade A). Ultrasound cervical length screening is recommended between 16 and 22 weeks for women with a singleton previously delivered before 34 weeks gestation, so that cerclage can be offered if cervical length <25mm before 24 weeks (Grade C). A cervical pessary is not recommended for the prevention of preterm birth in a general population of asymptomatic women with twin pregnancies (Grade A) or in populations of asymptomatic women with a short cervix (professional consensus). Although the implementation of universal screening by transvaginal ultrasound for cervical length at 18-24 weeks of gestation in women with a singleton gestation and no history of preterm birth can be considered by individual practitioners, this screening cannot be universally recommended. In cases of preterm labor, (i) it is not possible to recommend any one of the several methods (ultrasound of the cervical length, vaginal examination, or fetal fibronectin assay) over any other to predict preterm birth (Grade B); (ii) routine antibiotic therapy is not recommended (Grade A); (iii) prolonged hospitalization (Grade B) and bed rest (Grade C) are not recommended. Compared with placebo, tocolytics are not associated with a reduction in neonatal mortality or morbidity (LE2) and maternal severe adverse effects may occur with all tocolytics (LE4). Atosiban and nifedipine (Grade B), unlike beta-agonists (Grade C), can be used for tocolysis in spontaneous preterm labor without preterm premature rupture of membranes. Maintenance tocolysis is not recommended (Grade B). Antenatal corticosteroid administration is recommended for all women at risk of preterm delivery before 34 weeks of gestation (Grade A). After 34 weeks, the evidence is insufficiently consistent to justify recommending systematic antenatal corticosteroid treatment (Grade B), but a course of this treatment might be indicated in clinical situations associated with high risk of severe respiratory distress syndrome, mainly in case of planned cesarean delivery (Grade C). Repeated courses of antenatal corticosteroids are not recommended (Grade A). Rescue courses are not recommended (Professional consensus). Magnesium sulfate administration is recommended for women at high risk of imminent preterm birth before 32 weeks (Grade A). Cesareans are not recommended for fetuses in vertex presentation (professional consensus). Both planned vaginal and elective cesarean delivery are possible for breech presentations (professional consensus). Delayed cord clamping may be considered if the neonatal or maternal state allows (professional consensus).