ultrasound in infertility - obgyn. · pdf fileultrasound in infertility • disclosures:...

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Helen Kim

Ultrasound in InfertilityHelen H. Kim, MDSection ChiefReproductive Endocrinology and InfertilityObstetrics and GynecologyThe University of Chicago Medicine

June 2017

Helen Kim

Ultrasound in Infertility

• Disclosures: None

• Learning Objectives– Understand the basic process of in vitro fertilization (IVF)

– Understand process of ovarian follicle development

– Understand advances in ultrasound technology led to development of modern IVF

Helen Kim

Overall Causes of Infertility

Uterine and Cervical Factors

5%

Unexplained25%

Ovulatory Dysfunction

20%

Tubal and Peritoneal Disease

20%

Male Factor30%

Boston IVF Handbook of Infertility, 2002

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Helen Kim

Causes of Infertility: Female


5%

Unexplained25%


20%


20%

Male Factor30%


• Female factors: 45% of infertility

• Ultrasound can provide insights– Tubal and Peritoneal Disease

– Ovulatory Dysfunction

– Uterine and Cervical factors

Helen Kim

Infertility: Tubal and Peritoneal Disease

Cervical and Uterine Factors

5%

Unexplained25%


20%


20%

Male Factor30%


• Hydrosalpinx– Suggest tubal disease

• Endometrioma– Suggest other endometriosis

– Suggest adhesions

Helen Kim


5%

Unexplained25%


20%

Tubal and Peritotneal

Disease 20%

Male Factor30%

Infertility: Ovulatory Dysfunction

• Polycystic Ovary – Suggest irregular ovulation

– Rule out diminished ovarian reserve

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Helen Kim


5%

Unexplained25%


20%

Tubal and Periotneal Disease

20%

Male Factor30%

Infertility: Uterine Factors


• Uterine anomalies

• Myomas

• Intra‐uterine lesions– Polyps or myomas

Helen Kim


5%

Unexplained25%


20%

Tubal and Periotneal Disease

20%

Male Factor30%

Infertility: Uterine Factors


• Saline Infusion Sonography– Better define lesion

Helen Kim

Assisted Reproduction

• Test tube babies

• In Vitro Fertilization (IVF)

• Infertility treatment in which both oocytes and sperm are handled outside the body and embryos are generated in a laboratory

www.stewartsworld.com

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Helen Kim

1978: Human Birth After IVF• Indication

– Blocked tubes• C-Section

– Pre-eclampsia – @ 38.5 wks

• Louise Joy Brown– July 25, 1978 – 5 lb 12 oz• Steptoe PC,

Edwards RG.

– “We hope to publish further medical and scientific details in your column at a later date.”

Helen Kim 11

Helen Kim

IVF Procedure: 1978

• Laparoscopic oocyte retrieval (timed with natural cycle)

• Insemination in vitro

• Incubation of the embryo 2.5 days

• Transfer of 1 embryo into uterus

Organon Teaching Slide

Organon Teaching SlideOrganon Teaching SlideOrganon Teaching Slide

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Helen Kim

IVF: Early Days

• Lesley Brown conceived with 1st IVF cycle– Not typical

• Often no embryos to transfer– Oocyte not retrievable

• 0.3 oocytes per cycle

– Oocyte does not fertilize– Embryo does not divide

• Modern IVF depends on multiple oocytes– More oocytes more embryos– Select best embryos for transfer

Helen KimHelen Kim

Follicle Development in the Ovary

http://medcell.med.yale.edu/histology/ovary_follicle.php

Primary

Pre-antral

AntralPre-

ovulatory

Primordial

Besser, GM and Thorner MO, Comprehensive Clinical Endocrinology, 2002

Helen Kim

Primordial Preantral Follicle

• Hormone Independent– Granulosa Cells have no FSH receptors

• Continues thru‐out life

• Most preantral follices– Undergo atresia

• Preantral follicles– Granulosa cells express FSH receptors

Primary Follicle

Basal Lamina

Oocyte

Primordial Follicle

Granulosa Cell

Preantral Follicle

Zona Pellucida

Granulosa Cell


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Helen Kim

FSH “Rescues” Cohort

Oocyte

Granulosa Cell

Antral Follicle Basal Lamina

Antrum

Blood Vessel

Theca Cell

Zona Pellucida

FSH

LH

Point of Ovulation

• Promote Follicle Development– Granulosa cell proliferation– Development of antrum– Follicle growth


Helen KimHelen Kim

Follicle Development in the Ovary

Helen Kim

Dominant Follicle

Selection• Day 5‐7 FSH• Most follicles Atresia• Dominant Follicle Develops

FSH

LH

Estrogen

Progesterone

Point of Ovulation

Menses 5 14


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Helen Kim

Human Menopausal Gonadotropins

• Isolated from urine– Pooled from menopausal women

– Contains FSH and LH

• 1950: Pergonal 25 Serono– Registered in Italy

Lunenfeld B. Human Reprod Update, 2004

• 1963: First Pregnancy– Lunenfeld B. 1963, Treatment of

anovulation by human gonadotropins. J Int Fedn Gynecol Obstet 1, 153.

Helen Kim

HMG Injections Multiple Ovarian Follicles

• Sextuplets– Premature– Poor outcome

• Monitoring– Physical exam– Ultrasound not available

Helen Kim

HMG Ovarian HyperstimulationSyndrome (OHSS)

• 1961: 1st Fatality

• Beall SA, Decherney A, The History and Challenges Surrounding Ovarian Stimulation in the Treatment of Infertility. Fertil Steril 2012: 97: 795.

• Ovarian Enlargement• ↑ Capillary Permeability

– Ascites– Pleural effusions– Hemo‐concentration

– thrombosis

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Helen KimHelen Kim

1980: Tracking Follicle Development: Ultrasound and estradiol

Smith DH et al., Assessment of ovulation by ultrasound and estradiol levels during spontaneous and induced cycles. Fertil Steril; 33 (4): 387, 1980

Ylostalo P. et al. Measurement of the ovarian follicle by ultrasound in ovulation induction. Fertil Steril; 31 (6): 651, 1979

B: bladder; F: follicle; U: uterusC: cyst

Helen Kim

1981: 1st IVF Baby in United States1st IVF Birth Using Gonadotropins

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Jones HW et al., 1982. The program for in vitro fertilization at Norfolk, Fertil Steril 38: 14.

• Indication– Tubal disease

• C-Section• Elizabeth Jordan Carr

– December 28, 1981 – 5 lb 12 oz

Helen Kim

LH Surge: Positive Estrogen FeedbackFSH

LH

Estrogen

Progesterone

Point of Ovulation

Besser, GM & Thorner MO, Comprehensive Clinical Endocrinology, 2002

• Estrogen – Triggers LH surge

• With IVF– Many small follicles– High estradiol

• For IVF– Need pituitary

suppression• GnRH Agonist• GnRH Antagonist

– Prevent premature LH surge

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Helen KimHelen Kim

LH Needed for Oocyte Maturation

• Triggers ovulation

• Triggers final maturation– Meiosis resume

– Cumulus expands

• hCG used for IVF– Binds same receptor

– Issues• False positive pregnancy test

• Risk of ovarian hyperstimulation syndrome

Speroff L et al, Clinical Gynecologic Endocrinology and Infertility, 1999

Helen Kim

IVF Procedure: 1980

• Ovulation Induction (monitored by ULTRASOUND and estradiol)• Laparoscopic oocyte retrieval • Insemination in vitro• Incubation of the embryo 2.5 days • Transfer of 1 embryo into uterus



Helen Kim

• Baseline antral follicle count– Predict ovarian response

• Avoid Ovarian Hyperstimulation– Adjust medications– Cancel cycle

• Optimize cycle– Adjust medications

• Time oocyte retrieval– Maximize # mature eggs

• Follicles generally 18‐20 mm

– Fewer eggs from • Follicles < 12 mm• Follicles > 24 mm

IVF: Monitoring Follicle Development

8 days stimulation

Baseline

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Helen Kim

• Track daily follicle growth– Natural 1.0 – 1.4 mm– Gonadotropin 1.7 – 2.0 mm

• Follow hormone levels– Estradiol– LH– Progesterone

• Time hCG trigger– Oocyte retrieval in 36 hours

• Track endometrium– Freeze embryos or transfer?

Transvaginal Ultrasound and Hormone Levels Guide Clinical Management

10 days stimulation

10 days stimulation

Helen Kim


Endometrial Changes in Response To Estrogen and Progesterone

Estrogen Progesterone

Menses 5 14 21 28

Helen KimHelen Kim

IVF: Monitoring Endometrium

• Endometrial Thickness– No consensus regarding minimal

thickness for pregnancy• > 6 mm, 7 mm, 8 mm?• Pregnancy reported with 4 mm

– Thicker with gonadotropin tx– ? Optimal thickness

• < 14 mm? < 18 mm?

• Endometrial Pattern– Optimal is “triple‐line”– Positive and negative predictive

values for endometrial echo patterns are low

Baseline: Endometrium 4.3 mm

8 days of Stimulation: Endometrium 10.7 mm

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Helen Kim

IVF Procedure: 1980

• Ovulation Induction (monitored by ULTRASOUND and estradiol)• Laparoscopic oocyte retrieval • Insemination in vitro• Incubation of the embryo 2.5 days • Transfer of 1 embryo into uterus



Helen Kim

1981: Ultrasound Guided Oocyte Retrieval

• Transabdominal/Transvesical– Painful– 1981: Sector Scanner

• Lenz S et al, Collection of human oocytes for in vitro fertilization by ultrasonically guided follicular puncture. Lancet 1:1163

– 1983: Larger Linear Array• Wikland M et al, Collection of human oocytes by the use of sonography. Fertil Steril Vol 39 (5): 656

• Oocytes collected from 77% follicles

f: folliclent: needle tip

Helen Kim

• 1983: case report– Gleicher N et al, Egg Retrieval for in vitro

fertilization by sonographically controlled vaginal culdocentesis. Lancet 2: 508

• 1985: 124 retrievals– Full bladder; void after procedure– 2.2 oocytes/patient– Less pain than transabdominal– Simpler than laparoscopy– BUT ‐ precise location and puncture NOT

possible

– Dellenbach P et al, Transvaginal sonographicallycontrolled follicle puncture for oocyte retrieval. Fertil Steril Vol 44 (5): 656

1983: Transvaginal Oocyte Retrieval Guided by Transabdominal Ultrasound

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Helen Kim

1986: Transvaginal Oocyte Retrieval Guided by Transvaginal Ultrasound

• 1986: 61 patients– Transvaginal sector scanner– Empty bladder– 4.5 oocytes/procedure– Oocytes collected from 86% follicles

Feichtinger W and Kemeter P, Transvaginal sector scan sonography for needle guided transvaginal follicle aspiration and other applications in gynecologic routine and research. Fertil Steril Vol 45 (5): 722

Helen KimHelen Kim

Transvaginal Ultrasound Guided Retrieval

Davis OK, Rsenwaks Z in Adashi EY et al. Reproductive Endocinology, Surgery, and Technology. Lippincott-Raven, 1996

• Surgical Procedure– Follicle punctured

– Fluid aspirated

– Oocytes collected in tube


Van Voorhis B. N Engl J Med 2007;356:379-386

Helen KimHelen Kim

Ovaries on Day of hCG Trigger

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Helen Kim

IVF Procedure: 1986

• Ovulation Induction (monitored by ULTRASOUND and estradiol)• Transvaginal ULTRASOUND guided oocyte retrieval • Insemination in vitro• Incubation of the embryo 2.5 days • Transfer of 1 embryo into uterus



Helen Kim

IVF: Embryo Culture

Day 1 Day 2 Day 3 Day 5

• 1998: Commercial media for blastocyst culture

• 1978 IVF: Embryo transfer on day 2‐3• In Vivo

– Fertilization: in Fallopian tube– Uterine implantation: Day 5‐6 blastocyst embryo

Helen KimHelen Kim

Ultrasound to Guide Embryo Transfer

• Results– Improve pregnancy and live

birth rate (10 RCT)– May decrease ectopic

pregnancy

• Catheter placement– More than 1 cm from fundus

in upper/middle area of uterine cavity

• Disadvantages– Full bladder– 2nd operator

Mains L, and Van Voorhis, BJ, Optimizing the technique of embryo transfer, Fertility and Sterility, 2010, Vol 94: 785

ASRM Guideline: Performing the embryo transfer, 2017

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Helen Kim

Modern IVF Procedure

• Ovulation Induction (monitored by ULTRASOUND and estradiol)• Transvaginal ULTRASOUND guided oocyte retrieval • Insemination in vitro• Incubation of embryos 5‐6 days • Transfer of embryo(s) into uterus (with ULTRASOUND guidance)



Helen Kim

• 2010

• The Nobel Prize was awarded to Robert G. Edwards “for development of in vitro fertilization”

41

"Robert G. Edwards - Facts". Nobelprize.org. Nobel Media AB 2013. Web. 18 Nov 2013. <http://www.nobelprize.org/nobel_prizes/medicine/laureates/2010/edwards-facts.html>

Helen Kim

2010: Assisted Reproductive Technology in United States

• 443 Clinics

• 147,260 IVF Procedures– 16,531 Egg Donor Cycles– 859 Gestational Carrier Cycles– 1% used pre‐implantation genetic diagnosis

• Births– 1.5% births in United States– 47,090 Deliveries– 61, 564 infants

http://www.cdc.gov/art/ART2010/section1.htm

https://www.sartcorsonline.com/rptCSR_PublicMultYear.aspx?ClinicPKID=0

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Helen Kim

https://www.cdc.gov/art/pdf/2010‐report/ART_2010_National_Summary_Report.pdf

Live birth rate

Pregnancy rate

2010: Pregnancy Rate for Cycles Using Fresh Non‐donor Eggs or Embryos

Singleton live birth rate

Helen Kim

Ultrasound for Assisted Reproduction:Future Directions

• Time oocyte retrieval better to optimize number of mature eggs– Follicle volume?– Follicle vascularity?

• Assess uterine receptivity to optimize implantation and live birth rate– Endometrial volume?– Uterine blood flow?

Helen KimHelen Kim

Louise Brown and Elizabeth Carrto meet in Chicago on June 16, 2017

FridayPosted Mar 3, 2017 at 3:02 PM Updated Mar 3, 2017 at 3:04 PM

ultrasound in infertility - obgyn. · pdf fileultrasound in infertility • disclosures:...

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