The clinical approach to ovulation induction requires an understanding of the causes of anovulation. Check my detailed presentation to get detailed understanding.

1. ▪ Chairperson Elect ICOG –Indian College of OB/GY
▪ National Corresponding Editor-Journal of OB/GY of India JOGI
▪ National Corresponding Secretary Association of Medical Women, India
▪ Founder Patron & President –ISOPARB Vidarbha Chapter 2019-21
▪ Chairperson-IMS Education Committee 2021-23
▪ President-Association of Medical Women, Nagpur AMWN 2021-24
Dr. Laxmi Shrikhande
MBBS; MD(OB/GY);
FICOG; FICMU; FICMCH
Medical Director-
Shrikhande Fertility Clinic
Nagpur, Maharashtra
▪ Nagpur Ratan Award @ hands of Union Minister Shri Nitinji Gadkari
▪ Received Bharat excellence Award for women’s health
▪ Received Mehroo Dara Hansotia Best Committee Award for her work as Chairperson
HIV/AIDS Committee, FOGSI 2007-2009
▪ Received appreciation letter from Maharashtra Government for her work in the field of
SAVE THE GIRL CHILD
▪ Senior Vice President FOGSI 2012
▪ President Menopause Society, Nagpur 2016-18
▪ President Nagpur OB/GY Society 2005-06
▪Delivered 11 orations and 450 guest lectures
▪Publications-13 National & 11 International
▪Sensitized 2 lakh boys and girls on adolescent health issues

2. Letrozole Stimulation Protocols
for Non IVF Cycle
Dr Laxmi Shrikhande
Consultant –Shrikhande Hospital
Nagpur

3. Jose-Miller AB, et al. Am Fam Physician 2007;75:849-56,
857-8.
Major causes of Subfertility in couples

4. Clinical approach to ovulation induction
▪The clinical approach to ovulation induction requires an
understanding of the causes of anovulation.
The four most common ovulatory disorders include
▪Polycystic ovary syndrome (PCOS),
▪Hypogonadotropic hypogonadism (HA),
▪Primary ovarian insufficiency (POI), and
▪ Hyperprolactinemia

5. General principles of Ovulation Induction
▪The method of ovulation induction selected by the clinician should be
based upon the
▪ underlying cause of anovulation and
▪the efficacy,
▪costs,
▪risks,
▪patient burden, and
▪potential complications associated with each method as they apply to
the individual woman.

6. Why Pre Conception Counselling

7. Ideal Ovulation Induction Drug
7
Oral Administration
Minimal monitoring of cycle
No hostile effect on endometrium & cervical mucus
Better ovulation rate & pregnancy rate
Less risk of Ovarian hyperstimulation syndrome (OHSS) & multiple
pregnancy

8. When to start stimulation
?
▪Early follicular phase –Recruitment
▪Late follicular phase – Growth

9. LETROZOLE

10. Letrozole-When
3rd
generation aromatase inhibitor (AI)
Letrozole is now considered to be the drug of choice for ovulation
induction in women with PCOS.
Clomiphene citrate has been the first-line drug for this population for
many years, with metformin used as an alternative.
However, both clomiphene and metformin appear to be less
effective for live birth rates than letrozole .
Legro RS, Barnhart HX, Schlaff WD, et al. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med
2007; 356:551.

11. Letrozole regimen —
❑ Sequential dose escalation of 2.5, 5, and 7.5 mg if ovulation does not
occur on lower doses is widely used by reproductive endocrinologists.
Al-Fadhli R, Sylvestre C, Buckett W, et al. A randomized trial of superovulation with two different doses of letrozole. Fertil
Steril 2006; 85:161.
Legro RS, Brzyski RG, Diamond MP, et al. Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. N Engl
J Med 2014; 371:119.

12. Advantages over Clomiphene Citrate
Robert F. Casper and Mohamed F. M. Mitwally. J Clin Endocrinol Metab , March 2006, 91(3):760–771

13. Side effects —CC vs letrozole
❖ Common side effects included hot flashes in 33 percent of women
receiving clomiphene and
❖fatigue and dizziness in 22 and 12 percent, respectively, of women
taking letrozole.
Legro RS, Brzyski RG, Diamond MP, et al. Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. N Engl J Med
2014; 371:119.

14. Fetal safety —
❑A study comparing the incidence of congenital malformations in 911
newborns of women who conceived following treatment
with letrozole or clomiphene citrate did not find a statistically
significant difference .
Tulandi T, Martin J, Al-Fadhli R, et al. Congenital malformations among 911 newborns conceived after infertility treatment with letrozole or clomiphene
citrate. Fertil Steril 2006; 85:1761.
Forman R, Gill S, Moretti M, et al. Fetal safety of letrozole and clomiphene citrate for ovulation induction. J Obstet Gynaecol Can 2007; 29:668.
Akbari Sene A, Ghorbani S, Ashrafi M. Comparison of the pregnancy outcomes and the incidence of fetal congenital abnormalities in infertile women
treated with letrozole and clomiphene citrate. J Obstet Gynaecol Res 2018; 44:1036.
Tatsumi T, Jwa SC, Kuwahara A, et al. No increased risk of major congenital anomalies or adverse pregnancy or neonatal outcomes following letrozole
use in assisted reproductive technology. Hum Reprod 2017; 32:125.
Sharma S, Ghosh S, Singh S, et al. Congenital malformations among babies born following letrozole or clomiphene for infertility treatment. PLoS One
2014; 9:e108219.

15. LBW —
❖A follow-up study did observe a significant increase in low birth
weight infants with use of clomiphene .
❖Infants born after use of letrozole were similar in birth weight to
infants conceived spontaneously.
Forman R, Gill S, Moretti M, et al. Fetal safety of letrozole and clomiphene citrate for ovulation induction. J Obstet
Gynaecol Can 2007; 29:668.

16. Summary & Recommendations-Letrozole
Letrozole is first-line therapy over clomiphene citrate.
The starting dose is 2.5 mg administered days 3 to 7; this can be
titrated up to a maximum dose of 7.5 mg/day if ovulation has not
occurred.
•Both letrozole and clomiphene citrate are pregnancy category X.
•Based on the half-life of letrozole, administration in the early
follicular phase should result in clearance of letrozole before
implantation takes place.
•Nevertheless, as with any ovulation induction agent, one must
confirm that the patient is not pregnant before starting therapy.
Teede HJ, Misso ML, Costello MF, et al. Recommendations from the international evidence-based guideline for the assessment and
management of polycystic ovary syndrome. Fertil Steril 2018; 110:364.

17. Monitoring ovarian stimulation
Transvaginal ultrasound scanning :
✔ Number & size of follicles
✔ Pattern & thickness of endometrium

18. Trigger-when ?
▪HCG at 20-22 mm
▪Dose- 5000 -10,000 IU

19. Luteal Phase Support
Given empirically
In most letrozole and CC
cycles
Required
Definitely with use of
Gonadotrophins
AND
GnRH analogs - Agonist and Antagonist

20. Summary and recommendations
▪The method of ovulation induction selected by the clinician should be
based upon the underlying cause of anovulation and the efficacy,
costs, risks, burden of treatment, and potential complications
associated with each method as they apply to the individual woman.
▪For oligoovulatory women with PCOS undergoing ovulation
induction letrozole is first-line therapy over CC, regardless of the
patient's body mass index (BMI) (Grade 2B).
▪For obese women with PCOS, lifestyle changes and weight loss is an
initial strategy to restore ovulatory cycles (Grade 2B).

21. Summary and recommendations
If oral ovulation induction agents are unsuccessful in women with PCOS, then gonadotropin therapy should be
started.
Strict attention to follicle number is essential to avoid multiple gestation and ovarian hyperstimulation.
To minimize the risk of multiple gestation and OHSS in PCOS, gonadotropin treatment should be stopped if
there are an excess number of follicles or extremely high serum estradiol concentrations.
For women with primary ovarian insufficiency (POI; premature ovarian failure) no ovulation induction strategy
has been shown to be effective. However, in vitro fertilization (IVF) with donor oocytes has high success rates
For women with hyperprolactinemic anovulation,ovulation induction with dopamine agonists with
either bromocriptine or cabergoline (Grade 2C).
While there has been concern about a possible increased risk of ovarian cancer with ovulation induction drugs,
it appears that the risk may be due to the infertility itself rather than the medications used to treat it.
However, because one study suggested an increase after 12 cycles of clomiphene citrate, women should not
receive more than 12 cycles.
There does not appear to be an increased risk of breast cancer with ovulation induction drugs.

22. •Its not what you give ……
its the way you give it!

24. The Art of Living
Anything that helps
you to become
unconditionally happy
and loving is what is
called spirituality.
H. H. Sri Sri Ravishakar

26. My World of sharing happiness!
Shrikhande Fertility Clinic
Ph- 91 8805577600
shrikhandedrlaxmi@gmail.com