Table III.

Definitions and lay terms for the outcomes of the core outcome set.

Outcome (Per category)		Definition for COSAR	Source/Reference
Medical term	Lay term
Pain
Cyclic pelvic pain	Pain coming at the same time in the menstrual cycle	Cyclic pelvic pain is considered to be a subset of chronic pelvic pain that occurs in relation to the menstrual cycle. This includes pain during ovulation.	(Muse, 1990; Won and Abbott, 2010)
Dyschezia	Pain during toilet visit/when opening bowels	Painful or difficult defecation [COSAR: during menstruation]	International Working Group of AAGL, ESGE, ESHRE and WES (Tomassetti et al., 2021)
Dysmenorrhea	Painful periods	Painful periods	(RCOG, 2022)
Dyspareunia	Pain during sex	Pain associated with sexual activity.	COSAR Steering Committee
Non-cyclic, untriggered pelvic pain	Pelvic pain occurring without a trigger	Pain in pelvic area that does not occur in a regular, cyclic fashion and that is not caused by any obvious triggers recognized by the person with adenomyosis.	COSAR Steering Committee
Pelvic bulk/pressure symptoms	Feeling tightness or pressure in the pelvic area	Feeling tightness or pressure in the pelvic area	(Spies et al., 2002)
Radiating pain	Radiating pain	Radiating pain to the lower back and/or extremities during the menstruation	COSAR Steering committee
Urinary system
Urinary frequency	Needing to urinate often	Abnormally frequent urination (e.g. once every hour or two) is termed urinary frequency.	(Wrenn, 1990)
Menstrual bleeding
Blood flow volume	How heavy the menstrual bleeding is	The amount of vaginal bleeding during menstruation, which is considered heavy >80 ml, normal 5–80 ml and light <5 ml	FIGO (Munro et al., 2018)
Duration of bleeding	How many days the menstrual bleeding lasts	Prolonged menstrual flow >8 days, normal 4.5–8 days, shortened <4.5 days
Intermenstrual bleeding	Bleeding in between periods	Experiencing episodes of bleeding that occur between normally timed menstrual periods. (A) cyclic (predictable), (B) non-cyclic
Unscheduled bleeding on hormonal medication	Unplanned bleeding on hormonal medication	Unplanned bleeding on hormonal medication
Length/regularity of cycle	Time between periods
Reproductive outcomes
Infertility Core Outcome Set			(Duffy et al., 2020)
Live, correctly sited (eutopic) pregnancy	Pregnancy with a heartbeat, confirmed by ultrasound	A correctly sited pregnancy diagnosed by ultrasonographic examination of at least one foetus with a discernible heartbeat.	ESHRE (Kirk et al., 2020), (Duffy et al., 2020)
		Reporting: singleton, twin pregnancy, higher multiple pregnancy and which gestation the ultrasound examination was performed on. A twin pregnancy is counted as one pregnancy event.
Pregnancy loss, including:
Ectopic pregnancy	A pregnancy located in the wrong place (outside the cavity of the uterus)	Any pregnancy that is implanted outside the uterine cavity.	ESHRE (Kirk et al., 2020)
Miscarriage	Early pregnancy loss	The spontaneous loss of a correctly sited (eutopic) pregnancy prior to 20 completed weeks of gestational age. Miscarriage should be reported after a viable pregnancy has been confirmed by ultrasound.	(Duffy et al., 2020)
Stillbirth	When a baby is not alive when born.	The death of a foetus prior to the complete expulsion or extraction from its mother after 20 completed weeks of gestational age. The death is determined by the fact that, after such separation, the foetus does not breathe or show any other evidence of life, such as heartbeat, umbilical cord pulsation or definite movement of voluntary muscles.
Termination of pregnancy	Termination of pregnancy	Intentional loss of a correctly sited (eutopic) pregnancy, through intervention by medical, surgical or unspecified means.
Live birth	Live birth	The complete expulsion or extraction from a woman of a product of fertilization, after 20 completed weeks of gestational age; which, after such separation, breathes or shows any other evidence of life, such as heart beat, umbilical cord pulsation or definite movement of voluntary muscles, irrespective of whether the umbilical cord has been cut or the placenta is attached. A birth weight of 350 g or more can be used if gestational age is unknown.
Gestational age at delivery	At how many weeks of pregnancy the baby is born	The age of a foetus is calculated by the best obstetric estimate determined by assessments which may include early ultrasound, and the date of the last menstrual period, and/or perinatal details. In the case of assisted reproductive techniques, it is calculated by adding 14 days to the number of completed weeks since fertilization.
Birthweight	Birthweight	Birth weight should be collected within 24 h of birth and assessed using a calibrated electronic scale with 10-g resolution.
Neonatal mortality	Death of the baby before, during or shortly after birth	Death of a live born baby within 28 days of birth. This can be sub-divided into early neonatal mortality, if death occurs in the first 7 days after birth and late neonatal mortality, if death occurs between 8 and 28 days after birth.
Major congenital anomaly	A disorder the baby is born with	Structural, functional and genetic anomalies, that occur during pregnancy, and identified antenatally, at birth, or later in life, and require surgical repair of a defect, or are visually evident, or are life-threatening, or cause death.
Time to pregnancy leading to live birth	Time to pregnancy leading to live birth	See detailed definition and measurement in reference.
Additional outcomes
Mode of conception	Was fertility treatment needed to become pregnant	If a pregnancy occurred spontaneously or through any type of ART.	COSAR Steering Committee
Postpartum haemorrhage	Heavy bleeding during and after the delivery.	Postpartum haemorrhage (PPH) is defined as a blood loss of 500 ml or more within 24 h after birth.	(WHO, 2012)
Abnormal placentation	Placental complications	Abnormal formation, placental growth or adherence of the placenta in the uterus.	COSAR Steering Committee
Haematology
Anaemia	Low levels of haemoglobin (oxygen carriers) in blood	Anaemia is a condition in which the number of red blood cells or the haemoglobin concentration within them is lower than normal. In non-pregnant women the definitions for anaemia are (at sea level): Mild 110–119 g/l, moderate 80–109 g/l, severe <80 g/l	(WHO, 2011)
Life impact
Health-related QoL	Health impact on quality of life	Quality of life is the individuals’ perceptions of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns	CDC (Centers for Disease Control and Prevention, 2000) (Post, 2014)
		Health-related QoL was defined as ‘perceived physical and mental health over time’.
Sexual functioning	Sexual functioning	Sexual functioning is characterized by absence of difficulty moving through the stages of sexual desire, arousal and orgasm, as well as subjective satisfaction with the frequency and outcome of individual and partnered sexual behaviour.	(Masters and Johnson, 1966)
Coital bleeding	bleeding during or after sexual activity	Vaginal bleeding during or after sexual activity.	COSAR Steering Committee
Delivery of care
Patient adherence to treatment	How well a patient follows a treatment	Medication compliance (synonym: adherence): refers to the degree or extent of conformity to the recommendations about day-to-day treatment by the provider with respect to the timing, dosage and frequency. It may be defined as ‘the extent to which a patient acts in accordance with the prescribed interval, and dose of a dosing regimen’.	(Cramer et al., 2008)
Patient satisfaction with treatment	Patient satisfaction with treatment	Patient satisfaction expresses whether a patient’s expectations about a health encounter were met.	(Rockville, 2021)
Symptom relief rate (most bothersome symptom)	How much better the worst symptom gets	Extent to which a treatment relieves a symptom (most bothersome symptom must be pre-defined).	COSAR Steering Committee
Symptom Recurrence for any symptom	How long it takes for a symptom to come back	The return of a disease or the signs and symptoms of a disease after a period of improvement.	COSAR Steering Committee
Symptom Recurrence for most bothersome symptom	How long it takes for the worst symptom to come back.	The return of a disease or the signs and symptoms of a disease after a period of improvement (most bothersome symptom must be pre-defined).	COSAR Steering Committee
Lesion size	Size of adenomyosis lesion	The radiologically estimated size of the primary lesion, measured in three planes perpendicular to each other.	COSAR Steering Committee
Discomfort during procedure	Discomfort during procedure	Includes pain or other negative, bodily symptoms that are experienced while a procedure is performed. Is not applicable for procedures that require general anaesthesia.	COSAR Steering Committee
Recovery time	Recovery time after procedure	Return to normal activities after a medical procedure was performed.	COSAR Steering Committee
Need for re-intervention	Need for repeated or other treatment	Need to repeat a procedure for the same condition, planned or unplanned, or perform a different procedure due to complications or ineffectiveness of the first procedure.	COSAR Steering Committee
Length of hospital stay	Length of hospital stay*	Time from admission to discharge of patient.	(WHO and WHO Patient Safety, 2010)
Premature termination of procedure	Having to stop a procedure before it was finished	A procedure being stopped before it is finished, either due to patient discomfort, complications or technical problems.	(WHO and WHO Patient Safety, 2010)
Uterus volume	Volume (size) of the uterus	The volume of the corpus uteri, excluding the cervix uteri, calculated as d1 (cm)×d2 (cm)×d3 (cm)×0.523, where d1 is the length of the corpus, d2 is the largest anteroposterior diameter and d3 is the largest transverse diameter	MUSA (Van den Bosch et al., 2015)
Adverse outcomes
Harm: impairment of structure or function of the body and/or any deleterious effect arising there from. Harm includes disease, injury, suffering, disability and death.			(WHO and WHO Patient Safety, 2010)
Adverse reaction: unexpected harm resulting from a justified action where the correct process was followed for the context in which the event occurred.
Side effect: a known effect, other than that primarily intended, related to the pharmacological properties of a medication.
We suggest reporting the following incident types within COSAR: Clinical procedure, infections, medication/fluids
Surgical complications:
Complication (GRADE I)		Any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic or radiological interventions. Allowed therapeutic regimens are: drugs as antiemetics, antipyretics, analgesics, diuretics, electrolytes and physiotherapy. This grade also includes wound infections opened at the bedside	(Dindo et al., 2004)
Complication (GRADE II)		Requiring pharmacological treatment with drugs other than such allowed for grade I complications; Blood transfusions; total parenteral nutrition
Complication (GRADE III)		Requiring surgical, endoscopic or radiological intervention
		Grade IIIa: Intervention not under general anaesthesia
		Grade IIIb: Intervention under general anaesthesia
Complication (GRADE IV)		Life-threatening complication (including central nervous system complications) requiring IC/ICU management.
		Grade IVa: Single organ dysfunction (including dialysis)
		Grade IVb: Multiorgan dysfunction
Complication (GRADE V)		Death of a patient
Infections		Surgical Site Infections have three grades: superficial incisional, affecting the skin and subcutaneous tissue. deep incisional, affecting the fascial and muscle layers. organ or space infection, which involves any part of the anatomy other than the incision that is opened or manipulated during the surgical procedure, for example joint or peritoneum.	NICE (Welsh, 2008) CDC (Anderson et al., 2014)
Adverse drug reactions (ADR)		We advise to use the WHO adverse drug reaction terminology for the specific drug reactions. WHO classifies ADR into six classes: Type A reactions (dose-related)—exaggerated but otherwise normal pharmacological response to the effects of the medicines given at a therapeutic dose. The reaction is treated by reducing the dose or withholding the medicine and considering alternative therapy. Type B reactions (non-dose related)—bizarre and unpredictable response with no relation to the dose or pharmacological action of the medicine, that is often allergic in nature. They are uncommon but are often severe and cause high mortality. Type C reactions (dose-related and time-related)—chronic (long term) and related to cumulative dose. The reaction is treated by reducing the dose or withholding the medicine, which may have to be withheld for a long time. Type D reactions (time related)—delayed (i.e. have a lag time) after the use of a drug. They are uncommon but their treatment is often intractable. Type E reactions (withdrawal)—these reactions occur soon after the end of use (i.e. withdrawal) and are uncommon. The reaction is treated by reintroducing the medicine and then withdrawing it slowly. Type F reactions (unexpected failure of efficacy)—these reactions occur when there is a failure of efficacy. Such reactions are common, may be dose-related and are often caused by drug interactions. The reaction is treated by increasing the dose and considering the effects of concomitant therapy.	WHO Collaborating Centre for International Drug Monitoring (WHO, 2021)
Reporting items
Endometriosis present		Terminology regarding location and grade according to working group.	International Working Group of AAGL, ESGE, ESHRE and WES (Tomassetti et al., 2021)
Fibroids present		FIGO Classification	FIGO (Munro et al., 2018)
Chronic pelvic pain present		Chronic pelvic pain can be defined as intermittent or constant pain in the lower abdomen or pelvis of a woman of at least 6 months in duration, not occurring exclusively with menstruation or intercourse and not associated with pregnancy. It is a symptom not a diagnosis.	(RCOG, 2012)
Wish for future pregnancy		If the woman has, at the time of the treatment, an active or future wish to become pregnant.	COSAR steering group.
Classification of adenomyosis		An internationally accepted and accredited system to classify and describe disease.	COSAR steering group.
Previous treatment for adenomyosis		All treatment (including medical, surgical, interventional) that has been used to treat adenomyosis-related symptoms in the past.	COSAR steering group.
Outcomes that are recommended to report, but not mandatory
Costs of treatment	How much the treatment costs	Costs of treatment	COSAR steering group.
Patient costs	How much the patient must pay for a treatment	Direct out of pocket expenses for the patient.	COSAR steering group.
Cost-utility analysis	Value-for-money of treatment	Value for money. A specific healthcare treatment is said to be ‘cost-effective’ if it gives a greater health gain than could be achieved by using the resources in other ways.	NICE (Welsh, 2008)

AAGL, American Association of Gynecologic Laparoscopists; ESGE, European Society for Gynaecological Endoscopy; WES, World Endometriosis Society; RCOG, The Royal College of Obstetricians and Gynaecologists; NICE, National Institute for Health and Clinical Excellence; COSAR, Core Outcome Set in Adenomyosis Research; FIGO, International Federation of Gynecology and Obstetrics; WHO, World Health Organization; CDC, Centers for Disease Control.