Transcript endometriosis - International Institute for Restorative Reproductive

Surgical and Non-Surgical
Treatment of Endometriosis
Maciej Barczentewicz, Radosław Maksym, Magdalena Machlarz
IIRRM 11th Annual General Meeting 2014
& Restorative Reproductive Medicine Conference
Stratford-upon-Avon, UK | July 9th, 2014
Faculty Disclosure
Doctor Maciej E. Barczentewicz, MD
Male Fertility Support
Dr. Maciej E. Barczentewicz has listed no financial
33rd Annual Meeting of the American Academy of
interest/arrangement
that would
be considered
FertilityCare™ Professionals
Stratford-upon-Avon, UK | July 9-12, 2014
a conflict
of interest.
Maciej Barczentewicz, Wojciech Dzierżak
Surgical and Non-Surgical
Treatment of Endometriosis
Presentation Outline
• Update
• Critical appraisal
• Our Management
• Our results
• Case presentation
Endometriosis
Endometrial tissue is found outside the uterus
• Pelvic pain: dysmenorrhoea, dyspareunia, dyschezia
• Subfertility
• High Prevalence ( 4-20% )
• Incidence rate 1 per mille / year
• Limited treatment possibilities
• Ovarian cancer risk is 27-80% higher
Clinical types of endometriosis
• Subtle endometriosis : 1-3 mm superficial
• Typical endometriosis : 5-40 mm superficial lesions
• Cystic ovarian endometriosis
• Deep involved endometriosis
• Peritoneal Pockets or Allen en Master syndrome
Adenomyosis
Endosalphingiosis
Retrograde menstruation
Sampson JA. Peritoneal endometriosis due to the menstrual
dissemination of endometrial tissue into the peritoneal
cavity. Am J Obstet Gynecol 1927; 14:422-469.
Retrograde menstruation - physiologic
„Endometriosis does not exist. All women
have endometriosis”
J. Evers 1994, ESHRE
Endometriosis Theories
• Coelomic metaplasia
• Hormones
• Apoptosis Suppression and Alteration of
Endometrial Cell Fate
• Stem Cells
• Genetics
• Oxidative Stress and Inflammation
• Immune Dysfunction
Immune Dysfunction
women with endometriosis
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Presence of Immune complex antigen-antibody IgG & C3 complement in
endometrium Weed JC, Arquembourg PC 1980
Peripheral blood T cells low and B cells high activity , high antibodies syntesis
Stratseva 1980
High level of IgA & IgG anti-endometrial and anti-ovarian antibodies in
peripheral blood
Mathur 1982
Presence of Anti- phospholipid antibodies IgG and IgM in peripheral blood
Gleicher 1986
Women with endometriosis are at increased risk for a host of other diseases
including chronic fatigue syndrome, multiple sclerosis, lupus, underactive
thyroid, and rheumatoid arthritis National Institute of Child Health and Human
Development 2002
CD4⁺ CD25⁺ FOXP3⁺ regulatory T cells in peripheral blood and peritoneal fluid of
patients with endometriosis. Olkowska-Truchanowicz J, Maksym RB et al. 2013
High rate of allergies among women with endometriosis Matalliotakis 2012
Role of allergy and autoimmune infamantory diseases
(endometriosis):
• positive correlation between endometriosis and allergic manifestations,
including hay fever, sinus allergic rhinitis, and food allergy type 1
(immediate type hypersensitivity)
• women with endometriosis frequently suffer from autoimmune
inflammatory diseases, allergies and asthma
• study indicated a link between endometriosis and increased risk of
allergic autoimmune disorders (that should further be explored)
Matalliotakis et al., 2012; Bungum et al., 2014
Food hypersensitivity and IgG-dependent
immune reactions:
• No significant correlation between food hypersensitivity and fertility
problems
• IgG-dependent allergy affects about 45% of USA and Europe
population, and is twice as common in women than in men
• Immunotoxins : immune complexes formed with IgG antibodies and
fragments of dietary proteins cause systemic or local chronic
inflammation at low intensity
• No specific symptoms, possible changes in the clinical picture in the
course of the disease and localization of the lesions
• Delayed reactions : might occur 8-72 hours after the food consumption
Audit of York Nutritional Laboratory survey, conducted by the Department of Health Studies, University of York, on behalf of the British
Allergy Foundation. 2001, January
IgG-dependent food hypersensitivity and
chronic/autoimmune diseases:
Food-specific IgG & immune reactions
•Complement & anafilatoxin generation (C3a, C5a)
•Immune cells & release of proinflammatory cytokines (IL-1, IL-6, TNF-a), proteases,
ROS-mediated reactions
•Basophils and platelets & release of amines vasomotor
Chronic /autoimmune diseases
•Functional bowel disorders (e.g. Irritable bowel syndrome)
•Inflammatory bowel disease (e.g. Crohn’s Disease, Ulcerative colitis)
•Joint diseases (e.g. Rheumatoid arthritis)
•Respiratory disorders (e.g. Asthma, Chronic sinusitis)
•Dermatological disorders (e.g. Atopic dermatitis)
•Chronic medical conditions (e.g. Obesity, Atherosclerosis, Migraine headaches, Diabetes)
Sampson & McCaskill, 1985; Pelikan, 1988; Crowe & Perdue, 1992; Hazebons & et al., 1996; Aktinson & et al., 2004; Ress
& et al., 2005; Harman & Hart, 2007; Zuo & et al., 2007; Wilders & et al., 2008; Bentz & et al., 2010; Aply & et al., 2010;
Vitamin D deficiency – discussion:
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vitamin D role in the pathogenesis and treatment of endometriosis (an
immunomodulator and anti-inflammatory agent)
VDR and vitamin D metabolizing enzymes are found in endometrium
(normal cycling, eutopic and ectopic endometrium of women
with endometriosis)
the endometrium is a target of 1, 25 dihydroxyvitamin D actions
through regulation of specific genes and via immunomodulation.
the endometrium in endometriosis expresses dysregulation of
some vitamin D enzymes and receptors.
VDR-agonist was shown to reduce the development of endometriotic
lesions and recurrence (mouse model)
Sayegh et al, 2014; Bertone-Johnson et al., 2010; Du et al., 2005, Sayegha et al., 2013
Diagnosis and Treatment of Endometriosis
Treatment of Endometriosis
FIGURE 9.
Diagnosis and Treatment of Endometriosis
CAROLINE WELLBERY, M.D., Georgetown University School of Medicine, Washington, D.C
Am Fam Physician. 1999 Oct 15;60(6):1753-1762.
Algorithm for treating endometriosis based on presenting symptom of either pain or infertility. (Broken arrow = optional
Aktualne wytyczne
Grades of
Recommendations
A
Supporting evidence
Evidence from meta-analysis of randomized
controlled trials
B
Evidence from at least one controlled study
without randomization
C
Evidence from non-experimental descriptive
studies, such as comparative studies, correlation
studies, and case-control studies
D
Case reports
GPP
Evidence from expert committee reports or
opinions or clinical experience of respected
authorities, or both
Surgical and Non-Surgical
Treatment of Endometriosis
Our Management :
• Medical treatment : “good” CrMS chart, letrozol , LDN
• Diet
• Surgery – near contact LPS, LPT – cooperating surgeons in
Poland: Dr Dr: Baryła, Binkiewicz, Gałczyński, Gratkowski,
Klimas, Maksym, Ulman,
• Interventional Radiology: prof Małgorzata SzczerboTrojanowska, prof Jan Oleszczuk, Dr Waciński
• Psychotherapy ( some cases)
Role of diet and nutrients (endometriosis)
– our results, n= 61 (1):
Most frequently consumed foods:
•gluten grains: wheat bread, wheat pasta, wheat roll
•dairy products: cheese, sour cream, cottage cheese, cow's milk
•vegetables: potato, tomato
•fruits: apple, banana
Role of diet and nutrients (endometriosis)
– our results, n=61 (2):
Conclusions:
•too high intake of processing dairy products
•too high intake of processing cereal products
•excessive intake of cereal gluten
•too low intake of gluten-free cereals (including rice, millet,
buckwheat, amaranth)
•too low a variety of fruits and vegetables consumed
•too high intake of processed meat
•small intake: fish, legumes, nuts and seeds, unrefined oils
Distribution of food-specific IgG in
women with infertility & edometriosis
– our results, n= 124
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In patients with a diagnosis of female subfertility and coexisting
endomteriosis are elevated levels of food-specific IgG(1-4)
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The most common “female subfertility” food allergens identified by the
diagnostic tests for serum specific IgG(1-4) antibodies are: hen’s eggs
(90%), wheat (92%), gluten & other gluten cereals (58%) milk
(72%), corn (55%), yeast (51%)
FoodDetective test 46; ELISA IgG(1-4), (Cambridge Nutritional Sciences Ltd/
Genesis Diagnostics Ltd, UK)
Vitamin D deficeincy – our results, n=61
• Vitamin D deficiency: 91,8% (56)
11.5 % (7)
0 -10 ng/ml
45.9 % (28)
10 -20 ng/ml
34.4 % (21)
20 - 30 ng/ml
8,2 % (5)
30 - 80 ng/ml
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Vitamin D in the standard: 8,2 % (5)
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The average concentration of vitamin D: 18.7 ng / ml (4.6 ng / ml - 37.3
ng / ml)
Our Individual Dietetic Program consists of:
Quantitative and qualitative analysis of individual nutrition habits
Optimization of nutritional program
Recommendations for the preconception nutrition
Recommendations for the anti-inflammatory diet
Recommendations for the elimination and/or rotation diet
Recommendations for the nutrition in the coexisting diseases (on the
basis of current scientific data)
• Consideration of the possible interactions between nutrition and
medicines taken by the patients
• Supplementation (in regard to accompanying diseases, and /or elimination
diet)
• Recommendations for the healthy life style (sport activity, appropriate
sleeping time, sun exposition, avoiding the stress, prayer time)
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The expected benefits of dietary intervention
with our Individual Dietetic Program:
•Mute the allergic response and inflammation in the
digestive system
•Reduction and prevention of mucosal barrier dysfunction to
food allergens
•Improved gastrointestinal function and nutrient absorption
•Minimize the likelihood of pseudoallergic reactions
•Recovery of immune tolerance to the actually harmful food
CASE
PRESENTATION
Couple 1
Age of wife: 37
G-0 P-0
Age of husband: 40
• Efforts to conceive: 6 month
• Diagnosis on entry into NPT :
• ENDOMETRIOSIS Grade IV LPS 2011;
• Adhesions - frozen pelvis
• Large Bowel obstruction
• Endometriosis of urinary tract
• Hydronephrosis with left ureteral stricture
• Left fallopian tube occluded
Couple 1
G-0 P-0
CrMS from : 30.05.2012
NPT diagnosis: WIFE
• CA 125
178
• Hydrosalpinx
• Latent hyperprolactinemia
after MTC
PRL 490 IU/ml 4265 IU/ml
• Limited mucus MCS 6.9
• Low progesterone at Peak+7
• FOOD Intolerance
• treatment with bromocryptine, progesterone, vitaminD3
, LDN, Letrozole, ACC, Diet
Couple 1
G-0 P-0
Referal to surgery
Pope Paul VI Institute
Dr Hilgers Omaha , Nebraska USA
Couple 1
G-0 P-0
CrMS from : 30.05.2012
NPT diagnosis: HUSBAND
• SPERM ANALISYS 18.09.2012 sperms 32mln/ml
motility 34% morph 21% elevated viscosity
• Treatment : suplements; acetylcysteine 600 – fertile
period
• SPERM ANALISYS 13.11.2012 sperms 53mln/ml
motility 44% morph 29% norm viscosity
Couple 1
CrMS from :
G-0 P-0
30.05.2012
After 12 month of CrMS natural conception
Baby Girl 3680 g cesarian section 6.02.2014
CASE
PRESENTATION
Couple nr 2
G-0 P-0
Woman age 30
Man age 32
Infertility 6 years
Diagnosis on start: 21.10.2009
Male Infertility: sperm sample 2009: sperm count 0,0
Past medical history: Hodgkin's lymphoma CTX 2007
Female infertility: Endometriosis
LPS 2008 endometrioma AFS IV
Couple nr 2 G-0 P-0
CrMS from: 5.06.2010
Diagnosis in NPT: HUSBAND
Hypogonadism, Varicocele 4,5mm, Valsalva maneuver (-)
sperm sample 14.04.2010 : 0.06mln sperm, 15% mobility,
0%morphology, elevated viscosity
sperm sample 6.09.2010: 12mln sperm, 33% mobility,
18%morphology, elevated viscosity
treatment: acetylcysteine
sperm sample 4.04.2011
9mln sperm, 35% mobility, 3%morphology, normal viscosity
Treatment: tamoxifen, Testosterone undecanoate, zinc, alfa lipoic
acid, l-carnitine, selenium
Couple nr 2 G-0 P-0
CrMS from:
5.06.2010
sperm sample 10.12.2011 after 4 month tamoxifen, Testosterone
undecanoate
21mln sperm, 26% mobility, 18%morphology, elevated viscosity
Libido decrease, Hair loss
treatment: acetylcysteine, zinc, alfa lipoic acid, l-carnitine,
selenium
Couple nr 2
G-0 P-0
CrMS from:
5.06.2010
NPT Diagnosis: WIFE
• Abnormal bleeding
• Cervical Ectropion
• Latent hyperprolactinemia
mg
treatment bromocriptine 1.25
• Low progesterone
• Limited mucus
• Food Intolerance
• Treatment: clomiphene HCG 2500 Peak +3,5,7, Vitamin B6 ,
guaifenesin
• Electrocoagulation/Hypherfaction
Couple nr 2
CrMS from:
G-0 P-0
5.06.2010
NPT Diagnosis: WIFE
• Abnormal bleeding
• Cervical Ectropion
• Treatment: Policresulenum, Hyaluronan
• Near contact LPS 15.04.2011 Frozen pelvis, endometrioma
• Letrozole, Pre Seed
• Psychotherapy
Couple nr 2
CrMS from:
G-0 P-0
5.06.2010
• Natural conception 2-5.12.2011 (follicle tracking)
• Pregnancy test HCG (+) positive
• Ultrasound confirms presence of fetus
Couple 2
CrMS from:
G-0 P-0
5.06.2010
Baby girl 3600 g born August 12th 2012 Caesarian Section
Postpartum depression
Lactation 9 month
13.06.2014 charting start
CASE
PRESENTATION
Couple nr 3
G-0 P-0
Woman age 34
Man age 35
Infertility 12 years
Diagnosis on commencement of treatment:
LPS 2003 ENDOMETRIOSIS, LPS 2005 TUBAL OCCLUSION,
LPS 2010 ENDOMETRIOMA, adhesions, myoma, tubes patent
medical treatment: Danazol, GnRH Analoques, Femara 1x1
MALE: sperm count 43 mln motility 50%, 16 % morphology
IUI 2x
In vitro 1x 2005: 5 embryos, transfer 3, kryo 1
Couple nr 3
G-0 P-0
Couple nr 3
G-0 P-0
Creighton Model : 9.05.2011
NaPro Dgn: Wife
Multiple food intolerance including dairy milk, poultry egg,
wheat, gluten - low carbohydrates & elimination diet
latent hyperprolactinemia fasting PRL 9,7 ng/ 219 ng after MTC
vitamin D3 12,6 ng
treatment bromocriptin, metformin, vit D3, LDN
Couple nr 3
G-0 P-0 endometriosis IV grade
Couple nr 3
G-0 P-0
3rd cycle - natural conception
pregnancy test HCG (+) positive
Ultrasound confirms presence of fetus
GS 6w6d CRL 6w3d FHR (+)
Progesterone at 6 weeks: 36,1 ng/l estradiol 658 pmol/l
EDD 16.04.2012
27.03.2012 cc Baby girl 2400 g
Couple nr 3
G-0 P-0
Baby girl 2400 g born March 27th 2012 Caesarian Section
Research in course of realisation :
1.Quantitative and qualitative analysis of the nutrition of the
patients’ group with the fertility problems and coexisting
diseases:
• autoimmune thyroidis (Hashimoto’s disease)
• polycystic ovary syndrome (PCOS)
• endometriosis
2.Clinical evaluation of elimination diet based of the results of
IgG- dependent food hypersensitivity test (in the group of patients
with the fertility problems and diagnosed coexisting autoimune disease(s):
autoimmune thyroiditis and/or endometriosis)
Research in course of realisation :
3. Analysis of the serum D3 vitamin level (25-OH-D3) (in the
group of the women with infertility problems)
4. Establishment of the dietary standards in the diagnostics
and therapy of female infertility and coexisting diseases
5.Development of educational standards regarding the
dietary habits and life style in the preconception period of
women with infertility problems
6.Infertility & Psychology : Stress level and quality of marital bonding
7.Retrospective treatment outcome analisys
8.iNest – center Number 22 
Take home messages:
• Immune Dysfunction
• “Good” CrMS chart
• LDN
• Diet
• Surgery
Correspondence address:
Maciej Barczentewicz
Leśna 37
20-423 Lublin,
POLAND
phone: 0048 667 660 289
e-mail: [email protected]