| Literature DB >> 35984284 |
Malcolm G Munro1, Adam H Balen2, SiHyun Cho3, Hilary O D Critchley4, Ivonne Díaz5, Rui Ferriani6, Laurie Henry7, Edgar Mocanu8, Zephne M van der Spuy9.
Abstract
Ovulatory disorders are common causes of amenorrhea, abnormal uterine bleeding and infertility and are frequent manifestations of polycystic ovary syndrome (PCOS). There are many potential causes and contributors to ovulatory dysfunction that challenge clinicians, trainees, educators, and those who perform basic, translational, clinical and epidemiological research. Similarly, therapeutic approaches to ovulatory dysfunction potentially involve a spectrum of lifestyle, psychological, medical and procedural interventions. Collaborative research, effective education and consistent clinical care remain challenged by the absence of a consensus comprehensive system for classification of these disorders. The existing and complex system, attributed to the World Health Organization (WHO), was developed more than three decades ago and did not consider more than 30 years of research into these disorders in addition to technical advances in imaging and endocrinology. This article describes the development of a new classification of ovulatory disorders performed under the aegis of the International Federation of Gynecology and Obstetrics (FIGO) and conducted using a rigorously applied Delphi process. The stakeholder organizations and individuals who participated in this process comprised specialty journals, experts at large, national, specialty obstetrical and gynecological societies, and informed lay representatives. After two face-to-face meetings and five Delphi rounds, the result is a three-level multi-tiered system. The system is applied after a preliminary assessment identifies the presence of an ovulatory disorder. The primary level of the system is based on an anatomic model (Hypothalamus, Pituitary, Ovary) that is completed with a separate category for PCOS. This core component of the system is easily remembered using the acronym HyPO-P. Each anatomic category is stratified in the second layer of the system to provide granularity for investigators, clinicians and trainees using the 'GAIN-FIT-PIE' mnemonic (Genetic, Autoimmune, Iatrogenic, Neoplasm; Functional, Infectious and Inflammatory, Trauma and Vascular; Physiological, Idiopathic, Endocrine). The tertiary level allows for specific diagnostic entities. It is anticipated that, if widely adopted, this system will facilitate education, clinical care and the design and interpretation of research in a fashion that better informs progress in this field. Integral to the deployment of this system is a periodic process of reevaluation and appropriate revision, reflecting an improved understanding of this collection of disorders.Entities:
Keywords: anovulation; ovulatory disorders; ovulatory disorders classification; ovulatory dysfunction
Mesh:
Year: 2022 PMID: 35984284 PMCID: PMC9527465 DOI: 10.1093/humrep/deac180
Source DB: PubMed Journal: Hum Reprod ISSN: 0268-1161 Impact factor: 6.353
Figure 1.Participants by region, displayed as a percentage. Note: While there was representation from every region, Europeans comprised the majority.
Figure 2.Participants by age and gender. Note: The proportion of men versus women and the age distribution are displayed.
Figure 3.Participants by stakeholder representation. Note: Almost 60% of the participants represented national obstetrical and gynecological societies, while 19% were deemed ‘Experts at large’ based primarily on their contributions to the scientific literature. Journal and subspecialty representatives each comprised 9% of the participant pool.
Figure 4.Participants’ roles in their local institution or organization. Note: Each participant was asked to reveal their primary (left) and secondary (right) roles or responsibilities in their local institution or organization. Almost three-quarters were primarily involved in clinical care, and there were no individuals who reported that bench research or editorial activity was their primary role. More than one-third saw clinical research as their secondary role, while almost one-quarter reported teaching as their secondary responsibility.
Ovulatory Disorders Classification Delphi results: Round 1.
Note: There were 88 invitations and 46 respondents. The first seven questions of this round were included to determine the demographics of the cohort. Questions 8–44 were designed to explore the perceived need and utility for an ovulatory disorders classification system. For agreement, a mean score of 7 (green) was required with fewer than 15% disagreeing with a statement. In this round, there was agreement on all but questions 21, 33, 34, 37 and 42, which are shaded yellow in the table. Question 42 did not reach consensus because >15% (red) disagreed with the statement.
Ovulatory Disorders Classification Delphi results: Round 2.
Note: This 22-question round had 46 invitations and 41 respondents. Consensus (green) was obtained on statements 1–6, 8–12, 14, 16, 18, 20 and 22. The remaining statements were categorized as neutral (yellow) because there was no consensus disagreement.
PCOS, polycystic ovary syndrome.
Ovulatory Disorders Classification Delphi results: Round 3.
Note: This was the final pre-live-meeting poll, with 46 invitations and 38 respondents. Statements 4 and 5 reached the criteria for consensus (green); statements 1–3 failed to reach consensus (yellow), but there was no consensus disagreement (mean score ≤ 3.4).
Ovulatory Disorders Classification Delphi results: Round 4.
Note: Delphi round 4 followed the live meeting. There were 46 invitations and 39 respondents. For agreement, a mean score of 7 was required (green) with fewer than 15% disagreeing with a statement. Here there was strong support for the system design, although there was a lack of consensus (yellow) regarding the role of infections and inflammatory conditions as contributors to the genesis of ovulatory disorders. There was now consensus support for the potential role of ovarian neoplasms as a potential cause of ovulatory disorders.
Ovulatory Disorders Classification Delphi results: Lay round.
| Question no. | Lay round statements/questions | Mean score (1–9) | Disagree (%) | Neutral (%) | Agree (%) |
|---|---|---|---|---|---|
| 1 | Questions 1–3 were demographic questions. | ||||
| 2 | |||||
| 3 | |||||
| 4 | Ovulatory disorders refer to any alteration in normal ovulatory function in non-pregnant women who are in the usual reproductive years (between the date of the first menstrual period and that of menopause). | 7.2 | 10.0 | 10.0 | 80.0 |
| 5 | Ovulatory disorders are common causes of infertility (inability to conceive spontaneously, typically for more than 12 months). | 6.8 | 10.0 | 20.0 | 70.0 |
| 6 | Ovulatory disorders are common causes of abnormal menstrual bleeding in women during their reproductive years. This means some abnormality in the frequency, regularity, duration or volume of menstrual periods—or even absent periods. | 5.8 | 10.0 | 50.0 | 40.0 |
| 7 | There are many different causes or potential causes of ovulatory disorders, and it appears that the cause is often unknown. | 6.3 | 10.0 | 30.0 | 60.0 |
| 8 | Many of the causes or potential causes of ovulatory disorders are not well understood by girls and women. | 8.5 | 0.0 | 0.0 | 100.0 |
| 9 | A well-designed system for classification of ovulatory disorders would be useful for facilitating interactions between women or patients and healthcare providers. | 7.7 | 0.0 | 10.0 | 90.0 |
| 10 | A well-designed system for classification of ovulatory disorders should improve the design and interpretation of research. | 7.5 | 0.0 | 10.0 | 90.0 |
| 11 | The system presented seems understandable and provides a platform upon which a lay audience can gain insight into the possible causes of ovulatory disorders. | 4.9 | 44.0 | 22.2 | 33.3 |
Note: There were 11 invitations and 10 respondents. The first three items were for demographic purposes. For agreement, a mean score of 7 was required (green) with fewer than 15% disagreeing with a statement. There was a lack of consensus (yellow) regarding the potential role of ovulatory disorders in the cause of abnormal uterine bleeding as well as the notion that some causes of ovulatory disorders may be unknown. There was criticism regarding the system as presented, with a mean score of 4.9 and 44% disagreeing with the construct at that time as using language not accessible to a lay audience. These responses predated modifications in the graphical presentation of the system and the development of a patient orientation pamphlet.
Lay round comments.
| Technical language not accessible to all. |
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| Lay audience do not understand medical jargon. |
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| It is confusing that PCOS is in the left-hand column if it does not relate to any of the words in the right-hand column. |
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| As a lay person working for a patient advocacy group, I can understand the system presented. |
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| Would consider adding what those two columns (levels) are—anatomical/location (?), possible causes related to anatomical location. Also, would make it more clear visually which category from the right column relates to which category from the left one. |
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| If PCOS is an exception, it’s hard to understand why it’s in this column then (if we already have a category ‘Ovarian’). |
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| The pic is not very clear to understand by itself. It is more clear if I read the explanation at the beginning. |
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| If PCOS is not about anatomy and stands by alone and has different causes, maybe it would be better to put it a bit separately on the pic. Because at a first glance, it looks like the causes on the right are also PCOS causes. |
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| What I don’t personally understand is what is iatrogenic and idiopathic, and functional and how idiopathic is different from physiological. And if we speak of general audience (like women and girls) I would suggest explaining what each word means. What looks more or less understandable is endocrine, genetic, inflammatory, trauma. The rest would benefit from explanation in simple terms. |
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| As regards structure, it’s not clear why causes are somehow grouped in three groups. Do those groups pertain to each hypothalamic, pituitary and ovarian? It looks like each group is a group of causes for each ‘organ’. Not sure what you planned to showcase. |
PCOS, polycystic ovary syndrome.
Note: Comments reflecting the initial graphical presentation of the system. Changes in this presentation have been made without altering the actual content or design of the system.
Figure 5.Graphical depiction of the proposed FIGO Ovulatory Disorders Classification System. Note: After the individual is diagnosed with an ovulatory disorder, the core or first level of the system is the allocation to type I, II or III disorders according to their presumed primary source: hypothalamus, pituitary gland or ovary, respectively. PCOS comprises the type IV category and the criteria proposed by WHO are to be used to determine this categorization. The second level stratifies each anatomic category (types I–III) into the known or presumed mechanism according to the ‘GAIN-FIT-PIE’ mnemonic as appropriate and applicable. FIGO, International Federation of Gynecology and Obstetrics; GAIN-FIT-PIE, Genetic, Autoimmune, Iatrogenic, Neoplasm; Functional, Infectious and Inflammatory, Trauma and Vascular; Physiological, Idiopathic, Endocrine; PCOS, polycystic ovary syndrome; WHO, World Health Organization.
Figure 6.Disorders of ovulation exist on a spectrum that ranges from occasional failure to ovulate to chronic anovulation. Note: Typically, but not always these disorders manifest abnormalities in menstrual parameters, such as frequency, regularity, duration and volume of bleeding, and, in the case of chronic anovulation with amenorrhea. It is apparent that the luteinized unruptured follicle (LUF) and luteal out of phase (LOOP) disorders exist on a similar spectrum of varying frequency.
| Abnormal uterine bleeding (AUB) | Implicitly, non-gestational and in the reproductive years. Any alteration in the normal frequency, regularity, duration or volume of menstrual bleeding (including HMB) as well as intermenstrual bleeding and unscheduled bleeding with pharmaceutical agents designed to suppress menstrual function |
| Acute heavy menstrual bleeding | An episode of HMB of sufficient volume to require immediate therapy |
| Amenorrhea | A symptom—absence of menstrual bleeding in a girl or woman in the reproductive years |
| Anovulation | Failure to ovulate |
| Chronic abnormal uterine bleeding (AUB) | Symptoms of AUB for the majority of the past 6 months |
| Chronic ovulatory disorder | Evidence of an ovulatory disorder for the majority of the previous 6 months |
| Frequent menstruation | An AUB symptom—menstrual cycle of less than 24 days |
| Heavy menstrual bleeding (HMB) | An AUB symptom—excessive menstrual blood loss that interferes with a woman’s physical, social, emotional and/or material quality of life |
| Infrequent menstruation | An AUB symptom—menstrual cycle length of more than 38 days |
| Intermenstrual bleeding | An AUB symptom—uterine bleeding between regular menstrual periods |
| Irregular menstruation | An AUB symptom—menstrual cycle lengths that vary by more than 7 (ages of 18–25 and 42–45 years) to 9 days (ages of 26–41 years) |
| Luteinized unruptured follicle (LUF) | Physical failure of follicle rupture (oocyte release), with the luteinization and other endocrine features of the secretory phase of the menstrual cycle |
| Luteal out of phase (LOOP) event | Premature recruitment of a follicle in the luteal phase of a menstrual cycle |
| Menstrual cycle | The duration in days from the first day of one menstrual period to the first day of the next |
| Ovulation | The release of an oocyte (egg) from an ovarian follicle |
| Ovulatory disorder | Any alteration of ovulatory function in non-pregnant women in the usual reproductive years |
| Primary amenorrhea | Failure of onset of menstruation by the age of 15 years |
| Prolonged menstruation | An AUB symptom—a menstrual period lasting more than 8 days |
| Secondary amenorrhea | Absence of menstrual periods for more than 180 days in an individual who has had at least one spontaneous menses |
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| Ganesh | Acharya | Journal |
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| Georgios | Adonakis | Expert at large | N/A |
| Sadiah | Ahsan | National Society | Society of Obstetricians and Gynecologists of Pakistan |
| Taghreed | AIhaidari | National Society | Iraqi Society of Obstetrics & Gynecology |
| Tengiz | Asatiani | National Society | Georgian Obstetricians and Gynecologists Association |
| Ricardo | Azziz | Expert at large | N/A |
| Adam | Balen | Steering Committee | N/A |
| Michela | Bedard | Lay participant | Period.org |
| Jennifer | Blake | National Society | Society of Obstetricians and Gynecologists of Canada |
| Veronica | Chamy | National Society | National Society, Obstetrics and Gynecology Chile |
| Ying | Cheong | National Society | Royal College of Obstetricians and Gynaecologists |
| Vincent Y.T. | Cheung | National Society | Obstetrical & Gynaecological Society of Hong Kong |
| Si Hyun | Cho | Steering Committee | N/A |
| Hilary | Critchley | Steering Committee | N/A |
| Jose Teixeira | da Silva | Expert at large | Centro de Genetica Alberto Barros |
| Ivonne | Diaz | Steering Committee | N/A |
| Colin | Duncan | Subspecialty Society | Society for Reproduction and Fertility |
| Amelie | Ekersley | Lay participant | Clue |
| Roberto | Epifanio-Malpassii | National Society | Sociedad Panamenã de Obstetricia y Ginecología |
| Abimbola | Famuyide | Journal |
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| Rui | Ferriani | Steering Committee | N/A |
| Linda | Giudice | Subspecialty Society | WHO |
| Maargarita | Gurevich | Lay participant | Flo Health |
| Sioban | Harlow | Journal |
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| Roger | Hart | National Society | Royal Australian and New Zealand College of Obstetricians and Gynaecologists |
| Oskari | Heikinheimo | Expert at large | N/A |
| Laurie | Henry | Steering Committee | N/A |
| Sulaiman | Heylen | Subspecialty Society | South African Society of Reproductive Medicine and Gynaecological Endoscopy |
| Richard | Kennedy | Expert at large | N/A |
| Anna | Klepchuckova | Expert at large | N/A |
| Petr | Krepelka | National Society | Czech Gynecological and Obstetrical Society |
| Paul | le Roux | Subspecialty Society | African Federation of Fertility Societies |
| Kateryna | Levchenko | Lay participant | Flo Health |
| Dimitrios | Loutradis | National Society | Hellenic Obstetrical and Gynecological Society |
| Erica | Marsh | Subspecialty Society | American Society for Reproductive Medicine |
| Noni | Martins | Lay participant | Unfertility |
| Raj | Mathur | Subspecialty Society | British Fertility Society |
| Thabo | Matsaseng | Expert at large | N/A |
| Rui | Miguelote | Subspecialty Society | Portuguese Society of Reproductive Medicine |
| Edgar | Mocanu | Steering Committee | N/A |
| Malcolm | Munro | Steering Committee | N/A |
| Eugene | Ngoga | National Society | Rwanda Society of Obstetricians and Gynecologists |
| Michelle | Nisolle | Journal |
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| Robert | Norman | Subspecialty Society | The Australian NHMRC Centre of Research Excellence in Women’s Health in Reproductive Life (CRE-WHiRL) |
| Masanori | Ono | National Society | Japan Society of Obstetrics and Gynecology |
| Axelle | Pintiaux | National Society | Collège Royal des Gynécologues de Langue Française Belges |
| Gunda | Pristauz-Telsnigg | National Society | Austrian Society for Gynecology and Obstetrics |
| Diana | Ramasauskaite | National Society | Lithuanian Association of Obstetricians and Gynecologists |
| Pernille | Ravn | National Society | Danish Society of Obstetrics and Gynecology |
| Jose | Reis | National Society | Portuguese Society of Gynecology |
| Peter | Roos | Subspecialty Society | South African Menopause Society |
| Irena | Rozic | Subspecialty Society | Fertility Europe |
| Anibal | Scarella | National Society | Chilean Society of Obstetrics and Gynecology |
| Katsiaryna | Sharai | Lay participant | Flo Health |
| Alena | Shibut | Lay participant | Flo Health |
| Sony | Sierra | Subspecialty Society | Canadian Fertility and Andrology Society |
| Anne | Steiner | Expert at large | N/A |
| Dominic | Stoop | Subspecialty Society | Belgian Society of Reproductive Medicine |
| Bettina | Toth | National Society | Austrian Society for Gynecology and Obstetrics |
| Zephne | Van Der Spuy | Steering Committee | N/A |
| Saskia | Williams | Lay participant | Infertility Awareness Association of South Africa |
| Lauren | Wise | Expert at large | N/A |
| Anusch | Yazdani | Journal |
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| Liudmila | Zhaunova | Expert at large | N/A |
| Meggan | Zunckel | Lay participant | Infertility Awareness Association of South Africa |
| Karabo | Zwane | Lay participant | Hannah You Are Not Alone |
Did not receive invite, but reviewed process and results so could report to represented organization.