fertility treatments other than art · 2016-06-21 · fertility treatments other than art dr warren...
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![Page 1: Fertility Treatments other than ART · 2016-06-21 · Fertility Treatments other than ART Dr Warren SW Chan BSc(Med) (Hons I) MBBS (Hons I) FRANZCOG MRMed CREI Monash IVF Next Generation](https://reader033.vdocuments.site/reader033/viewer/2022042307/5ed3738387321e22e0482718/html5/thumbnails/1.jpg)
Fertility Treatments other than ARTFertility Treatments other than ART
Dr Warren SW Chan BSc(Med) (Hons I) MBBS (Hons I) FRANZCOG MRMed CREI
Monash IVF Next Generation Fertility | Westmead Fertility Centre
START Conference – Saturday 28th May 2016
VMO Westmead Hospital | VMO Royal Prince Alfred Hospital
W aevafem.com.au E [email protected]
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What is Infertility?
• 12 months of trying to conceive
• Incidence 1 in 6
• Increases with age
• 12 months of trying to conceive
• Incidence 1 in 6
• Increases with age
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What is Infertility?85% within 1 yr, 93% within 2 yrs
% pregnant
Months of trying
% pregnant
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Maternal Age & Spontaneous Conception
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Degrees of Fertility
Number of Mild FertilityFactors
Typical Monthly Chance Estimated Time to Pregnancy
0 20% 4 months0 20% 4 months
1 5% 2 years
2 1% 7 years
3 0.2% 40 years
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Degrees of Fertility
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The Role of a CREI SpecialistAdvice
• Weight loss – diet, exercise
• Smoking advice
• Pre-pregnancy advice
Reproductive surgery• Female
• Endometriosis & Fibroids
• Tubal re-anastomosis & salpingectomy
• Ovarian pathology/drilling
• Male
• Surgical sperm collection (PESA, TESA)
• Vasectomy reversals
Assisted Reproductive Techniques• OI (ovulation induction)
• Clomiphene/Letrozole, FSH
• IUI (intra-uterine insemination)
• IVF (in vitro fertilisation)
• ICSI (intra cytoplasmic sperm injection)
• PGD (pre-implantation genetic diagnosis)
• Donor gametes (sperm & eggs)
• Oocyte Vitrification (social egg freezing)
• Oncofertility (fertility preservation)
• Surrogacy
Advice• Weight loss – diet, exercise
• Smoking advice
• Pre-pregnancy advice
Reproductive surgery• Female
• Endometriosis & Fibroids
• Tubal re-anastomosis & salpingectomy
• Ovarian pathology/drilling
• Male
• Surgical sperm collection (PESA, TESA)
• Vasectomy reversals
Assisted Reproductive Techniques• OI (ovulation induction)
• Clomiphene/Letrozole, FSH
• IUI (intra-uterine insemination)
• IVF (in vitro fertilisation)
• ICSI (intra cytoplasmic sperm injection)
• PGD (pre-implantation genetic diagnosis)
• Donor gametes (sperm & eggs)
• Oocyte Vitrification (social egg freezing)
• Oncofertility (fertility preservation)
• Surrogacy
![Page 8: Fertility Treatments other than ART · 2016-06-21 · Fertility Treatments other than ART Dr Warren SW Chan BSc(Med) (Hons I) MBBS (Hons I) FRANZCOG MRMed CREI Monash IVF Next Generation](https://reader033.vdocuments.site/reader033/viewer/2022042307/5ed3738387321e22e0482718/html5/thumbnails/8.jpg)
Obesity & FertilityObesity & Fertility
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Female Fertility & BMI
• Overweight & obese women have (Maheshwari et al, Hum Reprod Update 2007; Bellver et al,Fertil Steril 2010)
• Reduced spontaneous ovulation• Increased time to conception• Decreased libido and coital frequency (Brewer et al, Reprod 2011)
• BMI >30 significantly associated with
• Higher FSH dose & fewer oocytes (Zander-Fox et al, Aust NZ J Obstet Gynaecol 2012)
• Decreased fertilisation rate by up to 45% (Brewer et al, Reprod 2011)
• Overweight & obese women have (Maheshwari et al, Hum Reprod Update 2007; Bellver et al,Fertil Steril 2010)
• Reduced spontaneous ovulation• Increased time to conception• Decreased libido and coital frequency (Brewer et al, Reprod 2011)
• BMI >30 significantly associated with
• Higher FSH dose & fewer oocytes (Zander-Fox et al, Aust NZ J Obstet Gynaecol 2012)
• Decreased fertilisation rate by up to 45% (Brewer et al, Reprod 2011)
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Female Fertility & BMI• Increased BMI associated with decreased pregnancy rates in ART (Bellver et
al, Fertil Steril 2007)
• BMI ≥25 decreased PR with IVF (OR 0.71; 95%CI 0.62-0.81) (Maheshwari et al,Hum Reprod Update 2007)
Wang et al, BMJ 2000
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MechanismsHow does Female Obesity
Impact Fertility?(Brewer et al, Reprod 2011)
MechanismsHow does Female Obesity
Impact Fertility?(Brewer et al, Reprod 2011)
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Challenges for Obesity in Pregnancy (RANZCOG 2013)
Intrapartum• Caesarean Section, Instrumental delivery
• Shoulder dystocia, PPH
• Anaesthetic risks
Postpartum• Wound infection
• Postnatal depression
• Long term Neonatal consequences – eg Obesity
Antenatal
Fetal
• Miscarriage
• Stillbirth
• Abnormal Fetal Growth
Maternal
• Gestational Diabetes
• Pre-eclampsia
• Thromboembolism
Intrapartum• Caesarean Section, Instrumental delivery
• Shoulder dystocia, PPH
• Anaesthetic risks
Postpartum• Wound infection
• Postnatal depression
• Long term Neonatal consequences – eg Obesity
Antenatal
Fetal
• Miscarriage
• Stillbirth
• Abnormal Fetal Growth
Maternal
• Gestational Diabetes
• Pre-eclampsia
• Thromboembolism
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Access to ART based on BMI
…“BMI ≥35 is a recognised risk factor inpregnancy and delivery and should be regarded
as a contra-indication to assisted fertility”……“inappropriate to recommend ovarianstimulation (including IVF) as part of first line
therapy in the female BMI>35 unless there areexceptional circumstances”…
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Male Obesity
Male Obesity leads to:
• Hypo-gonadotrophic, hyper-estrogenic hypo-androgenism
• Accumulation of endocrinedisruptors in adipose tissue
• Increased testicular temperature
• Increased sexual dysfunction
Male Obesity leads to:
• Hypo-gonadotrophic, hyper-estrogenic hypo-androgenism
• Accumulation of endocrinedisruptors in adipose tissue
• Increased testicular temperature
• Increased sexual dysfunction
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Male Obesity
• Male obesity alters spermparameters (Sermondade et al, HumReprod Update 2013; Hammoud et al, FertilSteril 2008)
• Sperm concentration• J shaped curve
• Decreased motility
• Increased DNA fragmentation
Sperm Concentration Abnormalities
• Male obesity alters spermparameters (Sermondade et al, HumReprod Update 2013; Hammoud et al, FertilSteril 2008)
• Sperm concentration• J shaped curve
• Decreased motility
• Increased DNA fragmentation
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Optimizing BMI Prior to IVF
• Decreases need for IVF – increases spontaneous conception
• Improves IVF success rates
• Decreases pregnancy complications
• Non-reproductive health benefits
• Decreases need for IVF – increases spontaneous conception
• Improves IVF success rates
• Decreases pregnancy complications
• Non-reproductive health benefits
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The Role of a CREI SpecialistAdvice
• Weight loss – diet, exercise
• Smoking advice
• Pre-pregnancy advice
Reproductive surgery• Female
• Endometriosis & Fibroids
• Tubal re-anastomosis & salpingectomy
• Ovarian pathology/drilling
• Male
• Surgical sperm collection (PESA, TESA)
• Vasectomy reversals
Assisted Reproductive Techniques• OI (ovulation induction)
• Clomiphene/Letrozole, FSH
• IUI (intra-uterine insemination)
• IVF (in vitro fertilisation)
• ICSI (intra cytoplasmic sperm injection)
• PGD (pre-implantation genetic diagnosis)
• Donor gametes (sperm & eggs)
• Oocyte Vitrification (social egg freezing)
• Oncofertility (fertility preservation)
• Surrogacy
Advice• Weight loss – diet, exercise
• Smoking advice
• Pre-pregnancy advice
Reproductive surgery• Female
• Endometriosis & Fibroids
• Tubal re-anastomosis & salpingectomy
• Ovarian pathology/drilling
• Male
• Surgical sperm collection (PESA, TESA)
• Vasectomy reversals
Assisted Reproductive Techniques• OI (ovulation induction)
• Clomiphene/Letrozole, FSH
• IUI (intra-uterine insemination)
• IVF (in vitro fertilisation)
• ICSI (intra cytoplasmic sperm injection)
• PGD (pre-implantation genetic diagnosis)
• Donor gametes (sperm & eggs)
• Oocyte Vitrification (social egg freezing)
• Oncofertility (fertility preservation)
• Surrogacy
![Page 18: Fertility Treatments other than ART · 2016-06-21 · Fertility Treatments other than ART Dr Warren SW Chan BSc(Med) (Hons I) MBBS (Hons I) FRANZCOG MRMed CREI Monash IVF Next Generation](https://reader033.vdocuments.site/reader033/viewer/2022042307/5ed3738387321e22e0482718/html5/thumbnails/18.jpg)
Reproductive SurgeryReproductive Surgery
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What is Reproductive Surgery?
• Surgery that improves Spontaneous Conception
• Surgery that improves Assisted Conception
• Surgery that improves Fertility Preservation
• Surgery that improves Spontaneous Conception
• Surgery that improves Assisted Conception
• Surgery that improves Fertility Preservation
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What is Reproductive Surgery?
Tulandi T et al. Redefining reproductive surgery. J Min Inv Gynecol. 2012; 19(3): 296-306
Male Surgery
Surgical Sperm retrievalVas reversals
Embryo “surgery”
Pre-implantation Genetic Diagnosis
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Fertility Surgery
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Endometriosis & FertilityEndometriosis & Fertility
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EndometriosisWhere do you find the latest recommendations?
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Endometriosis
• Incidence• 5-10% in normal population• Up to 50% of infertile women
• Presentation• Pain• Infertility
• Reduced monthly fecundity from 15-20% to 2-10%• ASRM Stage 1-2 endometriosis halves spontaneous conception rates
• 30% asymptomatic
• Incidence• 5-10% in normal population• Up to 50% of infertile women
• Presentation• Pain• Infertility
• Reduced monthly fecundity from 15-20% to 2-10%• ASRM Stage 1-2 endometriosis halves spontaneous conception rates
• 30% asymptomatic
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UterusUterus
Normal appearingOvary & tube
Normal appearingOvary & tube
Blood vesselson Pelvic Side
Wall
Blood vesselson Pelvic Side
Wall
Pouch of DouglasPouch of Douglas
Uterosacral LigamentsUterosacral Ligaments
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ASRM Stage 1 EndometriosisASRM Stage 1 Endometriosis
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ASRM Stage 2-3 EndometriosisASRM Stage 2-3 Endometriosis
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Bowel Adhesiondissected free
Bowel Adhesiondissected free
Endometriomaresected
EndometriomaresectedPelvic side wall endometriosis excisedPelvic side wall endometriosis excised
Bowel Adhesiondissected free
Bowel Adhesiondissected free
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Endometriosis - PathophysiologyASRM Stage 1 & 2How does this cause infertility?
• Increased E2• P4 Resistance• Increased Prostaglandins• Altered Immune Response• Aberrant Cytokine Profile
• VEGF, IL-1β, IL-6, IL-8 & TNFα
Pro-inflammatory products have toxic effects on:• Oocytes• Embryo• Tubal Motility• Endometrial receptivity
ASRM Stage 1 & 2How does this cause infertility?
• Increased E2• P4 Resistance• Increased Prostaglandins• Altered Immune Response• Aberrant Cytokine Profile
• VEGF, IL-1β, IL-6, IL-8 & TNFα
Pro-inflammatory products have toxic effects on:• Oocytes• Embryo• Tubal Motility• Endometrial receptivity
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ASRM Stage 4 EndometriosisASRM Stage 4 Endometriosis
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Endometriosis – PathophysiologyASRM Stage 3 & 4How does this cause infertility?
In addition to pro-inflammatory effects:
• Anatomical distortion• Pelvic adhesions & endometriomas• Impair oocyte release & tubal transport
• Impairs ovarian reserve
• Poorer outcomes compared with early stage diseasein ART
• Symptoms are not stage specific, but ART outcomesare stage specific
ASRM Stage 3 & 4How does this cause infertility?
In addition to pro-inflammatory effects:
• Anatomical distortion• Pelvic adhesions & endometriomas• Impair oocyte release & tubal transport
• Impairs ovarian reserve
• Poorer outcomes compared with early stage diseasein ART
• Symptoms are not stage specific, but ART outcomesare stage specific
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Endometriosis - ManagementASRM Stage 1 & 2
What is the evidence?
Spontaneous Conception
ART
• 2 RCT’s• Marcoux et al (N Eng J Med 1997) – Increased PR (OR 2.06 95%CI
1.28-3.33)• Gruppo Italiano (Hum Reprod 1999) – no significant difference• Meta-analysis (Cochrane 2010) – Increased LBR (OR 1.64 95%CI
1.05-2.57)
• No RCT’s
ASRM Stage 1 & 2
What is the evidence?
Spontaneous Conception
ART
• 2 RCT’s• Marcoux et al (N Eng J Med 1997) – Increased PR (OR 2.06 95%CI
1.28-3.33)• Gruppo Italiano (Hum Reprod 1999) – no significant difference• Meta-analysis (Cochrane 2010) – Increased LBR (OR 1.64 95%CI
1.05-2.57)
• No RCT’s
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Endometriosis - ManagementASRM Stage 1 & 2
Surgical excision preferred over ablation
• RCT for pain (Healey et al. Fertil Steril 2010) – no significant difference• No trials studying fertility
• Excision may be superior• Histological diagnosis• Complete resection of disease• Decrease in adhesion formation• Lower recurrence rate
Surgical excision preferred over ablation
• RCT for pain (Healey et al. Fertil Steril 2010) – no significant difference• No trials studying fertility
• Excision may be superior• Histological diagnosis• Complete resection of disease• Decrease in adhesion formation• Lower recurrence rate
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Endometriosis – Management
ASRM Stage 3 & 4What is the evidence?
• No RCT’s
• Surgical excision improves pregnancy rates 30-67%(uncontrolled studies)
• Second line surgery reduces pregnancy rates by 50%compared with first line surgery (ACCEPT 2012)
ASRM Stage 3 & 4What is the evidence?
• No RCT’s
• Surgical excision improves pregnancy rates 30-67%(uncontrolled studies)
• Second line surgery reduces pregnancy rates by 50%compared with first line surgery (ACCEPT 2012)
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Endometriosis – Management
ASRM Stage 3 & 4 Second line surgery reduces pregnancy rates by 50%compared with first line surgery (ACCEPT 2012)
ASRM Stage 3 & 4
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ASRM Stage 4 Bowel EndometriosisASRM Stage 4 Bowel Endometriosis
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Bowel nodule dueto endometriosis
Bowel Resection &Anastomosis
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Endometriosis - ManagementEndometriomas
What is the evidence?
Spontaneous Conception
ART
• Excision preferred over drainage – decreased recurrence• Excision increases spontaneous pregnancy rates (OR 5.21
95%CI 2.04-13.29) (Hart et al. Cochrane 2008)
• Controversial• No clear evidence for removal of endometriomas for
infertility alone
Endometriomas
What is the evidence?
Spontaneous Conception
ART
• Excision preferred over drainage – decreased recurrence• Excision increases spontaneous pregnancy rates (OR 5.21
95%CI 2.04-13.29) (Hart et al. Cochrane 2008)
• Controversial• No clear evidence for removal of endometriomas for
infertility alone
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Normal appearingLeft Ovary & tubeNormal appearingLeft Ovary & tube EndometriomaEndometrioma
UterusUterus
Bowel & Omental AdhesionsBowel & Omental Adhesions
ASRM Stage 4Endometriosis
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Endometriosis - Summary
• ASRM Stage 1-2• Surgical treatment improves spontaneous conception• Excision preferred over ablation
• ASRM Stage 3-4• Individualize treatment
• Endometriomas• Individualize treatment• Excision preferred over ablation/aspiration• Limit electro-surgery for hemostasis – minimize reduction in ovarian reserve
• ASRM Stage 1-2• Surgical treatment improves spontaneous conception• Excision preferred over ablation
• ASRM Stage 3-4• Individualize treatment
• Endometriomas• Individualize treatment• Excision preferred over ablation/aspiration• Limit electro-surgery for hemostasis – minimize reduction in ovarian reserve
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Fibroids & FertilityFibroids & Fertility
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Fibroids
Where do you find the latest recommendations?
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Fibroids – Effects on Fertility
• Anatomical Distortion
• Affects gamete transport
• Decreased endometrial receptivity
• Altered myometrial contractility• Altered endometrial blood supply• Localised endometrial inflammation & abnormal cytokine profile
• Anatomical Distortion
• Affects gamete transport
• Decreased endometrial receptivity
• Altered myometrial contractility• Altered endometrial blood supply• Localised endometrial inflammation & abnormal cytokine profile
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Fibroids - Classification
• Sub-mucosal
• Intra-mural• Sub-serosal
• T0 – pedunculated• T1 – <50% intramural extension• T2 – >50% intramural extension
How does this help with management?
• Sub-mucosal
• Intra-mural• Sub-serosal
• T0 – pedunculated• T1 – <50% intramural extension• T2 – >50% intramural extension
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Fibroids & Fertility
Sub-mucosal
Intra-mural
Sub-serosal
• Are associated with reduced fertility and increased miscarriage rates• Approx 65-70%
• May be associated with infertility and increased miscarriage rates• Approx 20%
• Do not have significant effect on fertility
Fibroid Effects on Fertility
Sub-mucosal
Intra-mural
Sub-serosal
• Are associated with reduced fertility and increased miscarriage rates• Approx 65-70%
• May be associated with infertility and increased miscarriage rates• Approx 20%
• Do not have significant effect on fertility
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Fibroids & Fertility
Sub-mucosal
Intra-mural
• Hysteroscopic myomectomy appears likely to improve fertility outcomes
• Insufficient evidence whether surgical management affects fertility outcomes
Fibroids – Surgical Management
Sub-mucosal
Intra-mural
• Hysteroscopic myomectomy appears likely to improve fertility outcomes
• Insufficient evidence whether surgical management affects fertility outcomes
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Fibroids & Fertility
• Infertile women with sub-mucosal fibroids• Hysteroscopic myomectomy improves fertility
outcomes by 2 fold
• Infertile women with symptomatic fibroids
• Infertile women who have multiple failed ART cycleswith intramural fibroids
Indications for Myomectomy in Infertile Women
• Infertile women with sub-mucosal fibroids• Hysteroscopic myomectomy improves fertility
outcomes by 2 fold
• Infertile women with symptomatic fibroids
• Infertile women who have multiple failed ART cycleswith intramural fibroids
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Operative Hysteroscopy – Other Indications
Operative Hysteroscopy can beused to improve fertilityoutcomes
• Congenital anomalies• Uterine Septum
• Acquired anomalies• Endometrial Polyps• Asherman’s Syndrome
Operative Hysteroscopy can beused to improve fertilityoutcomes
• Congenital anomalies• Uterine Septum
• Acquired anomalies• Endometrial Polyps• Asherman’s Syndrome
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Tubal Disease & FertilityTubal Disease & Fertility
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Hydrosalpinx
Infertility Sequelae due to PID
• 1 infection – 30%• 2 infections – 60%• 3 infections – 90%
Infertility Sequelae due to PID
• 1 infection – 30%• 2 infections – 60%• 3 infections – 90%
• Chlamydia, gonorrhea, anaerobes• Can be asymptomatic
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Hydrosalpinx
What are your options?
• Do nothing
• Salpingectomy
• Other:• Tubal Occlusion (Filschie Clip)• Essure• Tubuloplasty
What are your options?
• Do nothing
• Salpingectomy
• Other:• Tubal Occlusion (Filschie Clip)• Essure• Tubuloplasty
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HydrosalpinxSalpingectomy vs Conservative Management (Cochrane 2010)
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HydrosalpinxSalpingectomy vs Tubal Occlusion (Cochrane 2010)
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Hydrosalpinx – Summary
• Decreases IVF success rates by 50%
• Doubles miscarriage rates
• Salpingectomy• Laparoscopic salpingectomy increases Live Birth Rate (OR 2.13, 95%CI
1.24-3.65) prior to IVF (Cochrane 2010)
• Excise close to Fallopian Tube to minimize compromising vascular supplyto ovary (minimize possible/theoretical decrease in ovarian reserve)
• Tubal Occlusion• Similar results compared with salpingectomy
• Decreases IVF success rates by 50%
• Doubles miscarriage rates
• Salpingectomy• Laparoscopic salpingectomy increases Live Birth Rate (OR 2.13, 95%CI
1.24-3.65) prior to IVF (Cochrane 2010)
• Excise close to Fallopian Tube to minimize compromising vascular supplyto ovary (minimize possible/theoretical decrease in ovarian reserve)
• Tubal Occlusion• Similar results compared with salpingectomy
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Hydrosalpinx – Summary
• Hysteroscopic Tubal Occlusion (Essure)
• Case series only – more studies required• Use after informed consent for patients not suitable for laparoscopy
• Fimbrioplasty, Tubuloplasty, Neo-salpingostomy
• Consider if “good prognosis” features• Hydrosalpinx <3cm diameter, thin tubal wall, preserved mucosal
folds
• Hysteroscopic Tubal Occlusion (Essure)
• Case series only – more studies required• Use after informed consent for patients not suitable for laparoscopy
• Fimbrioplasty, Tubuloplasty, Neo-salpingostomy
• Consider if “good prognosis” features• Hydrosalpinx <3cm diameter, thin tubal wall, preserved mucosal
folds
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Microsurgery• Tubal Re-anastomoses• Vasectomy Reversals
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Microsurgical Tubal Re-anastomoses
• 5% request rate
• Up to 40-70% Pregnancy Rates
• Microsurgical vs Laparosocpic
• 5% request rate
• Up to 40-70% Pregnancy Rates
• Microsurgical vs Laparosocpic
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Tubal Reversal – Summary
• Good evidence of its effectiveness• Compares favourably with IVF (but no RCT’s)• Microsurgical vs Laparoscopic
• Recommend in:• Young women• Older women without other fertility factor where IVF success
rates are reduced (likely previous proven fertility)
• Good evidence of its effectiveness• Compares favourably with IVF (but no RCT’s)• Microsurgical vs Laparoscopic
• Recommend in:• Young women• Older women without other fertility factor where IVF success
rates are reduced (likely previous proven fertility)
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Vasectomy Reversal
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Microsurgical Vasectomy Reversal – Results
• Female Partner
• Duration of vasectomy
• <3yrs – 97% patency, 71% LBR• >15yrs – 76% patency, 30% LBR• Overall – 85% patency, 50% LBR
• Best results if no or low levels anti-sperm antibodies
• Female Partner
• Duration of vasectomy
• <3yrs – 97% patency, 71% LBR• >15yrs – 76% patency, 30% LBR• Overall – 85% patency, 50% LBR
• Best results if no or low levels anti-sperm antibodies
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The Future – Robotics Surgery
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Final RemarksFinal Remarks
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Final Remarks
• Fertility care ≠ IVF
• Surgical treatments assist in improving outcomes of both spontaneousconception & IVF
• Lifestyle modifications are vital in improving chances of spontaneousconception & IVF success
• Fertility care ≠ IVF
• Surgical treatments assist in improving outcomes of both spontaneousconception & IVF
• Lifestyle modifications are vital in improving chances of spontaneousconception & IVF success
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Final Remarks
• IVF will help the large majority of women under 38 years of age
• If success is to be attained, it will usually be so within three stimulationcycles
• Overall success rates can be up to 50-60% per cycle
• IVF will help the large majority of women under 38 years of age
• If success is to be attained, it will usually be so within three stimulationcycles
• Overall success rates can be up to 50-60% per cycle
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Thankyou – any questions?Thankyou – any questions?
Dr Warren SW Chan BSc(Med) (Hons I) MBBS (Hons I) FRANZCOG MRMed CREI
Monash IVF Next Generation Fertility | Westmead Fertility Centre
VMO Westmead Hospital | VMO Royal Prince Alfred Hospital
W aevafem.com.au E [email protected]
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Endometriosis - ManagementEndometriomas
What is your surgical approach?
Endometriomas
What is your surgical approach?
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Cyst attachedto Bowelomentum
Cyst attachedto Bowelomentum
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Fibroids - Imaging
Optimal Imaging for Endometrial Cavity Involvement