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Lubna Pal, MBBS, FRCOG, MS. FACOG Professor & Interim Chief, Reproductive Endocrinology & Infertility Department
Lubna Pal, MBBS, FRCOG, MS. FACOG Professor & Interim Chief, Reproductive Endocrinology & Infertility Department

Lubna Pal, MBBS, FRCOG, MS. FACOG Professor & Interim Chief, Reproductive Endocrinology & Infertility Department of Obstetrics, Gynecology & Reproductive Sciences Yale University School of Medicine New Haven, CT, USA

lubna.pal@yale.edu

AMAG Advisory Board member Natera Advisory Board member Abbott Advisory Board member GLG-consultant

USA lubna.pal@yale.edu AMAG Advisory Board member Natera Advisory Board member Abbott Advisory Board member GLG-consultant
Gametes Timeliness Presence Quality Access N o r m a l c y Seed 2/26/2018
Gametes Timeliness Presence Quality Access N o r m a l c y Seed 2/26/2018

Gametes

Timeliness

Presence

Quality

Access

Normalcy

Seed

Gametes Timeliness Presence Quality Access N o r m a l c y Seed 2/26/2018 Soil

2/26/2018

Soil

Preparation

Quality

Normalcy

Gametes Timeliness Presence Quality Access N o r m a l c y Seed 2/26/2018 Soil

Hypothalamo-Pituitary Ovarian Signaling

E2

Ovary

Hypothalamo-Pituitary Ovarian Signaling E2 Ovary NPY Leptin Insulin Kisspeptin Neurokinin B Dynorphin Prolactin TRH

NPY

Leptin

Insulin

Kisspeptin

Neurokinin B

Dynorphin

Prolactin

TRH

Anterior Pituitary

E2

90 80 70 60 50 40 30 20 10 0 P<0.05 Missed abortion N 267
90 80 70 60 50 40 30 20 10 0 P<0.05 Missed abortion N 267

90

80

70

60

50

40

30

20

10

0

90 80 70 60 50 40 30 20 10 0 P<0.05 Missed abortion N 267 Live

P<0.05

Missed90 80 70 60 50 40 30 20 10 0 P<0.05 abortion N 267 Live birth

abortion

N 267

Live birth90 80 70 60 50 40 30 20 10 0 P<0.05 Missed abortion N 267 N

N 285

30 20 10 0 P<0.05 Missed abortion N 267 Live birth N 285 Missed Abortion at
Tubal flushing for subfertility (Review); 2015 The Cochrane Collaboration. NEJM 2017; 376: 2043-2-52
Tubal flushing for subfertility (Review); 2015 The Cochrane Collaboration. NEJM 2017; 376: 2043-2-52
Tubal flushing for subfertility (Review); 2015 The Cochrane Collaboration. NEJM 2017; 376: 2043-2-52

Tubal flushing for subfertility (Review); 2015 The Cochrane Collaboration.

Tubal flushing for subfertility (Review); 2015 The Cochrane Collaboration. NEJM 2017; 376: 2043-2-52

NEJM 2017; 376: 2043-2-52

6500 IVF Cycles; 419 (6.4%) in women with BMI >30 (mean 33.6). Bellver J et
6500 IVF Cycles; 419 (6.4%) in women with BMI >30 (mean 33.6). Bellver J et
6500 IVF Cycles; 419 (6.4%) in women with BMI >30 (mean 33.6). Bellver J et

6500 IVF Cycles; 419 (6.4%) in women with BMI >30 (mean 33.6).

Bellver J et al, Female obesity impairs in vitro fertilization outcome without affecting embryo quality.Fertil Steril 2010;93:447–54

413 women conceived following Single Blast Transfer -Fresh (n 325) -FET (n 88) Normal BMI
413 women conceived following Single Blast Transfer -Fresh (n 325) -FET (n 88) Normal BMI
413 women conceived following Single Blast Transfer -Fresh (n 325) -FET (n 88) Normal BMI

413 women conceived following Single Blast Transfer -Fresh (n 325) -FET (n 88)

Normal BMI (18.5–24.9) : 244 Raised BMI ( ≥25): 169

BMI ≥25 increased risk of clinical miscarriage <23 weeks

Fresh SBT (AOR 2.7, 95% CI 1.5–4.9) FET SBT (AOR 6.8, 95% CI 1.5–31.1)

Adjustment covariates: Age, duration & cause of infertility, previous miscarriage, smoking status & quality of blastocyst replaced.

Rittenberg V et al. 2011, Hum Repd, 26;2642–2650.

BMI Normal (18.5 – 24.9), Overweight (25.0 – 29.9), Obese (≥ 30 kg/m 2 ).
BMI Normal (18.5 – 24.9), Overweight (25.0 – 29.9), Obese (≥ 30 kg/m 2 ).
BMI Normal (18.5 – 24.9), Overweight (25.0 – 29.9), Obese (≥ 30 kg/m 2 ).

BMI Normal (18.5 – 24.9), Overweight (25.0 – 29.9), Obese (≥ 30 kg/m 2 ). Multivariate analysis included paternal & maternal BMI. Letters denote significance at p < 0.05. Spermatogenesis. 2012 ; 2(4): 253–263.

NTD Risk if Maternal BMI 30-39.9 vs. <25 NTD Risk if Maternal BMI >=40 vs.

NTD Risk if Maternal BMI 30-39.9 vs. <25

NTD Risk if Maternal BMI >=40 vs. <25

vs. <25 NTD Risk if Maternal BMI >=40 vs. <25 Rasmussen. SA et al., Maternal obesity

Rasmussen. SA et al., Maternal obesity and risk of neural tube defects. Am J Obstet Gynecol 2008 ;198(6):611-9.

Smoking & ART Outcome – CP per cycle

Smoking & ART Outcome – CP per cycle Waylen AL, et al. Hum Reprod Update 2009;15:31–44.

Waylen AL, et al. Hum Reprod Update 2009;15:31–44.

. RCT, 12 week intervention with 2gram Myoinositol + folic acid 200mg versus folic acid
. RCT, 12 week intervention with 2gram Myoinositol + folic acid 200mg versus folic acid
. RCT, 12 week intervention with 2gram Myoinositol + folic acid 200mg versus folic acid
. RCT, 12 week intervention with 2gram Myoinositol + folic acid 200mg versus folic acid

.

RCT, 12 week intervention with 2gram Myoinositol + folic acid 200mg versus folic acid alone. Artini P et al. Endocrine and clinical effects of myo-inositol administration in polycystic ovary syndrome.

Smoking & ART Outcome- Miscarriage Risk

Smoking & ART Outcome- Miscarriage Risk Waylen AL, et al. Hum Reprod Update 2009;15:31–44.

Waylen AL, et al. Hum Reprod Update 2009;15:31–44.

Likelihood for LB was increased 4-fold (OR, 4.5; 95% CI, 1.27, 15.72; P .02) for
Likelihood for LB was increased 4-fold (OR, 4.5; 95% CI, 1.27, 15.72; P .02) for
Likelihood for LB was increased 4-fold (OR, 4.5; 95% CI, 1.27, 15.72; P .02) for
Likelihood for LB was increased 4-fold (OR, 4.5; 95% CI, 1.27, 15.72; P .02) for

Likelihood for LB was increased 4-fold (OR, 4.5; 95% CI, 1.27, 15.72;

P .02) for women with 25OHD levels

>45 ng/mL

(>112.5 nmol/L)

Pal L et al. J Clin Endocrinol Metab. 2016 Aug;101(8):3027-35.

218 patients resistant to Clomid randomized to short (Letrozole 5mg daily x 5 days) versus
218 patients resistant to Clomid randomized to short (Letrozole 5mg daily x 5 days) versus

218 patients resistant to Clomid randomized to short (Letrozole 5mg daily x 5 days) versus long ( 2.5mg daily x 10 days) protocol. 455 Rx cycles

Metformin during ovulation induction with gonadotrophins followed by timed intercourse or intrauterine insemination for
Metformin during ovulation induction with gonadotrophins followed by timed intercourse or intrauterine insemination for
Metformin during ovulation induction with gonadotrophins followed by timed intercourse or intrauterine insemination for

Metformin during ovulation induction with gonadotrophins followed by timed intercourse or intrauterine insemination for subfertility associated with polycystic ovary syndrome (Review) (Rev Copyright © 2017 The Cochrane Collaboration.

 Preparation › Progesterone  Timing, formulation, route, dose › Cycle parameters  Agonist vs

Preparation

Progesterone

Timing, formulation, route, dose

Cycle parameters

Agonist vs antagonist

Peak estradiol - less is more!

Trigger

GnRH agonist

Thickness

Normalcy?

Hydrosalpinx

Fibroids

Endometriosis

Adenomyosis

Adhesions

Polyps

Endometritis

(n=194) (n=145) Gynecol Endocrinol, 2013; 29(12): 1026–1030
(n=194) (n=145) Gynecol Endocrinol, 2013; 29(12): 1026–1030
(n=194) (n=145) Gynecol Endocrinol, 2013; 29(12): 1026–1030
(n=194) (n=145)
(n=194)
(n=145)

Gynecol Endocrinol, 2013; 29(12): 1026–1030

ART Endometrial injury in women undergoing assisted reproductive techniques. Cochrane Database Syst Rev. 2015 Mar
ART Endometrial injury in women undergoing assisted reproductive techniques. Cochrane Database Syst Rev. 2015 Mar

ART

ART Endometrial injury in women undergoing assisted reproductive techniques. Cochrane Database Syst Rev. 2015 Mar

Endometrial injury in women undergoing assisted reproductive techniques. Cochrane Database Syst Rev. 2015 Mar 22;(3):CD009517.

IUI

CP Livebirth
CP
Livebirth

Fertility and Sterility 2018 109, 84-96.e4DOI:

(10.1016/j.fertnstert.2017.09.021)

 Intrauterine instillation › Growth Hormone › Platelet Rich Plasma  Uterine stem cell enrichment
 Intrauterine instillation › Growth Hormone › Platelet Rich Plasma  Uterine stem cell enrichment

Intrauterine instillation

Growth Hormone

Platelet Rich Plasma

Uterine stem cell enrichment

Hematopoietic mobilization

Bone marrow infusion /injection

Rich Plasma  Uterine stem cell enrichment › Hematopoietic mobilization › Bone marrow infusion /injection
• Optimize spontaneous conception • Weight loss • Stress reduction • Smoking cessation • Timeliness

Optimize spontaneous conception

Weight loss

Stress reduction

Smoking cessation

Timeliness of coitus

Folic acid

Tubal flushing?

Myoinositol

Vitamin D supplementation

Individualize fertility treatment through judicious utilization of strategies

Extended protocol

Insulin sensitizers

Elective embryo cryopreservation

Progestin regimen

Ovarian suppression prior to ET