The clinical approach to ovulation induction requires an understanding of the causes of anovulation.

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. Clomiphene Citrate
Ovarian Stimulation
Protocol for Non IVF Cycle
Dr Laxmi Shrikhande
Consultant –Shrikhande Hospital
Nagpur

3. Unexplained
28%
Male factors
24%
Ovarian
dysfunction
21%
Tubal factors
14%
Other
13%
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. Ovulation induction - When
 Ovulation induction is the method for treating
anovulatory infertility1
 The World Health Organization (WHO) categorises
ovulation disorders into three groups
 Patients eligible for ovulation induction belong
either to WHO group I or to WHO group II
Messinis IE. Hum Reprod 2005;20(10):2688–2697;
https://www.ncbi.nlm.nih.gov/books/NBK327781/ as accessed on 24th nov 2018,
Group Gonadotropin levels Estrogen
secretion
Cause
I Low Low Hypothalamic-pituitary
failure
II Normal Normal Hypothalamic-pituitary-
ovarian axis failure
III High Low Ovarian failure

6. Most experts have moved away from the WHO
Most experts have moved away from the World Health Organization (WHO)
terminology which assign women to three categories of anovulation:
WHO class 1 – Hypogonadotropic hypogonadal anovulation
WHO class 2 – Normogonadotropic normoestrogenic anovulation (almost
all women in this category have polycystic ovary syndrome [PCOS]), when
using the Rotterdam criteria for the diagnosis of PCOS . This is the most
common cause of anovulation.
WHO class 3 – Hypergonadotropic hypoestrogenic anovulation (primary
ovarian insufficiency [POI; premature ovarian failure])
Hyperprolactinemia did not have a separate WHO category.

7. Hypogonadotropic Hypogonadism —
 Hypothalamic causes of hypogonadotropic hypogonadism include
functional hypothalamic amenorrhea (FHA) and isolated gonadotropin-
releasing hormone (GnRH) deficiency.
 Multiple factors may contribute to the pathogenesis of FHA, including
eating disorders (such as anorexia nervosa), exercise, and stress.
 Although rare, hypogonadotropic hypogonadism presenting as primary
amenorrhea can be due to complete congenital GnRH deficiency.
 This syndrome is called idiopathic hypogonadotropic hypogonadism or, if it
is associated with anosmia, Kallmann syndrome.
 Many infiltrative diseases and tumors of the hypothalamus and pituitary
can also result in hypogonadotropic hypogonadism (due to diminished
GnRH release or gonadotropin deficiency).

8. Copyrights apply
Polycystic Ovary Syndrome —

9. Primary Ovarian Insufficiency —POI
 POI, formerly referred to premature ovarian failure (POF) and
defined as menopause before age 40 years, occurs in only 1 percent
of all women but accounts for 5 to 10 percent of cases of anovulation.
In most cases, the follicle pool is exhausted due to accelerated follicle
loss of unknown origin
The only effective option is IVF with donor oocytes.
Women with POI have other important health issues related to their
estrogen deficiency, including an increased risk of osteoporosis and
cardiovascular disease if estrogen is not replaced.

10. Hyperprolactinemic Anovulation —
 Hyperprolactinemia accounts for 5 to 10 percent of women with
anovulation.
 These women are anovulatory because hyperprolactinemia inhibits
gonadotropin secretion, presumably by inhibiting GnRH.
 Most have oligomenorrhea or amenorrhea.
 Their serum gonadotropin concentrations are usually normal or
decreased.

11. Goals of Ovulation Induction
Induce mono follicular rather than multi follicular development and
subsequent mono ovulation and,
ultimately, a singleton pregnancy and
birth of a healthy newborn .

12. 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.

13. Why Pre Conception Counselling

14. What is Preconception Counseling —
 Preconception care is a broad term that refers to the process of
identifying
 social, behavioral, environmental, and biomedical risks to a woman's
fertility and pregnancy outcome
 and then reducing these risks through education, counseling, and
appropriate intervention.

15. What Pre conception advice should be given
 BMI
 BP
 Lifestyle counselling
 Garbh sanskar spiritual
 Folic acid supplimentation
 Anemia correction if detected
 Sugar / Thyroid
 Correction of endocrine factors
 Thalassemia screen wherever indicated

16. Pre-conceptional counseling-Vaccination
 FOGSI recommends vaccination counseling as a part of
pre-pregnancy counseling (unvaccinated women)
 History of occurrence of vaccine preventable diseases,
previous vaccinations administered and allergic reactions
to vaccinations must be recorded.
 Rubella ,Hepatitis B and Varicella vaccination should be
given preferably during postmenstrual period
 Pregnancy should be deferred for 3 months in case of
Rubella vaccine

17. Ideal Ovulation Induction Drug
17
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

18. Ovarian Stimulation Protocols
Clomiphene
Letrozole
CC + Gonadotrophins.
Letrozole + Gonadotrophins
Gonadotrophins
Gonadotrophins and antagonists

19. When to start stimulation ?
 Early follicular phase –Recruitment
 Late follicular phase – Growth

20. CLOMIPHENE

21. Clomiphene citrate
 Drug of choice in women with oligoovulatory and anovulatory cycles
 1st line treatment for OI for >55 yrs
 Simple to use
 Cost effective
 Fewer complications
Casper RF, et al. J Clin Endocrinol Metab. 2006; 91: 760-771.; Banerjee Ray P, et al. Arch Gynecol Obstet. 2012 Mar;285(3):873-7.;
Pavone ME, et al. J Clin Endocrinol Metab. 2013 May; 98(5): 1838–1844.

22. 2 stereoisomers of CC
The commercially available form of clomiphene is the dihydrogen citrate
salt (clomiphene citrate).
It contains two stereoisomers: zu-clomiphene (38 percent) and en-
clomiphene (62 percent), which were originally called the cis-isomer and
trans-isomer, respectively.
 En-clomiphene is cleared rapidly, while zu-clomiphene has a long half-life .
The two clomiphene isomers have mixed estrogenic and antiestrogenic
effects that vary among species.
En-clomiphene is the more potent isomer with greater antiestrogenic
activity and the one primarily responsible for inducing follicular
development .

23. Depletion of ER in pituitary &
hypothalamus due to prolonged
stimulation
Estrogen feedback loop gets
interrupted
FSH secretion increased leading to
multiple follicle growth
Clomiphene citrate: Mechanism of action
Casper RF, et al. J Clin Endocrinol Metab. 2006; 91: 760-771.

24. Patient selection
 The primary indication for the antiestrogen clomiphene citrate is
infertility secondary to oligoovulation or anovulation .
 Some amount of endogenous estrogen is necessary for a response to
clomiphene; women with PCOS do produce estrogen (as evidenced by
spontaneous menses or withdrawal bleeding in response to
a progesterone challenge).
 Women who are hypoestrogenemic are unlikely to respond (eg, those
with hypogonadotropic amenorrhea or primary ovarian insufficiency)

25. Ovulatory disorder-confirmation
 Pre treatment evaluation — Before initiating therapy, the presence of
ovulatory dysfunction must be established.
 The menstrual history alone may be diagnostic (eg, one can be
confident that ovulatory dysfunction is present in women with
amenorrhea or irregular menses [>45 day intermenstrual interval]).
 If the diagnosis of ovulatory dysfunction is uncertain, additional
testing should be performed.
 This can include simple, noninvasive tests such as basal body
temperature and/or urinary luteinizing hormone (LH) monitoring,
although a luteal phase serum progesterone level is more definitive.

26. Copyrights apply
Ovulatory disorder-confirmation

27. Patient selection
Disorders of
 pituitary,
 adrenal, and
 thyroid origin that can cause anovulation
 should be excluded prior to the initiation of therapy as
 targeted treatment of these endocrinopathies can result in normal
ovulation.

28. The pre treatment evaluation should include :
A complete history and physical examination.
Semen analysis of the partner to identify seminal abnormalities that might
contribute to the infertility.
A pelvic examination or a pelvic ultrasound to rule out ovarian cysts,
especially in patients with known tendency to form functional cysts.
Hysterosalpingogram if the clinical history suggests uterine or tubal
pathology may also be present and in women over 35 years of age to avoid
ineffective treatment when fertility is in decline. In women with no risk
factors for tubal disease, the hysterosalpingogram can be postponed but
should be performed if women have not conceived after three ovulatory
cycles
Ovarian Reserve Tests- Maternal age / AFC / AMH ??

29. When to start CC —
 Typically started on the D2/D3 of a cycle, following either
spontaneous or induced bleeding.
However, the results of therapy (in terms of ovulatory rates,
pregnancy, or spontaneous miscarriage) are comparable when
clomiphene is started on cycle day 2, 3, 4, or 5 .
Wu CH, Winkel CA. The effect of therapy initiation day on clomiphene citrate therapy. Fertil Steril 1989; 52:564.
Dehbashi S, Vafaei H, Parsanezhad MD, Alborzi S. Time of initiation of clomiphene citrate and pregnancy rate in polycystic
ovarian syndrome. Int J Gynaecol Obstet 2006; 93:44.

30. What dose —
 There are no laboratory or clinical parameters that predict the dose necessary to
achieve ovulation.
 The initial dose, empirically, is 50 mg daily for five days; starting with a higher
dose does not result in higher pregnancy rates.
 If ovulation does not occur in the first cycle of treatment, the dose is increased to
100 mg.
 Thereafter, the dose is increased by increments of 50 mg to a maximum daily
dose of 150 mg (100 mg is the maximum dose approved by the US Food and Drug
Administration [FDA], and the American Society for Reproductive Medicine
[ASRM] suggests that doses >100 mg add little to clinical pregnancy rates) .
 Once ovulation is achieved, the same dose should be continued for four to six
cycles.
Practice Committee of the American Society for Reproductive Medicine. Use of clomiphene citrate in infertile women: a
committee opinion. Fertil Steril 2013; 100:341.

31. CC Failure failure & CC resistance
Failure of ovulation is “clomiphene resistance”,
About 20-25% of anovulatory women are CC-resistant
Whereas failure of pregnancy despite ovulation is “clomiphene-
failure” .

32. When to stop CC-
 Because of the observations that pregnancy rates are low after six cycles
of treatment and that 12 or more cycles may increase the risk of ovarian
neoplasms ,
 the American College of Obstetricians and Gynecologists (ACOG) has
suggested that clomiphene treatment be limited to fewer than 12 cycles
and that the number of gonadotropin cycles be minimized, as well .
 Further evaluation and/or a change in therapy for women who do not
conceive after three to six ovulatory CC cycles is recommended
Rossing MA, Daling JR, Weiss NS, et al. Ovarian tumors in a cohort of infertile women. N Engl J Med 1994; 331:771.
ACOG Committee on Practice Bulletins-Gynecology. ACOG Practice Bulletin. Clinical management guidelines for obstetrician-
gynecologists number 34, February 2002. Management of infertility caused by ovulatory dysfunction. American College of Obstetricians
and Gynecologists. Obstet Gynecol 2002; 99:347.

33. How to monitor CC cycle—TIC
• The response to treatment should be monitored.
• Determination of the ovulatory LH surge by urinary LH kits is what most clinicians
recommend in practice.
• Urinary LH monitoring also provides information on appropriate timing of
intercourse during a given cycle .
• The LH surge typically occurs 5 to 12 days after clomiphene administration is
completed. Ovulation generally occurs 14 to 26 hours after the detection of the
urinary LH surge and almost always within 48 hours .
• Therefore, the interval of highest fertility is the day of the LH surge and the
following two days.
O'Herlihy C, De Crespigny LJ, Robinson HP. Monitoring ovarian follicular development with real-time ultrasound. Br J Obstet
Gynaecol 1980; 87:613.
Miller PB, Soules MR. The usefulness of a urinary LH kit for ovulation prediction during menstrual cycles of normal women.
Obstet Gynecol 1996; 87:13.

34. Monitoring —
 A basal body temperature chart can also be used and does not
increase the cost of treatment. Conversion of a uniphasic to a
biphasic basal temperature curve suggests retrospectively that
ovulation has occurred. However, basal body temperature charting
can be tedious for some patients and is not useful for timing of
intercourse, as the temperature rise occurs one to five days after the
midcycle LH surge and up to four days after ovulation.
 A mid-luteal (one week after ovulation or one week before the
expected menses) serum progesterone concentration greater than 3
ng/mL (ideally greater than 10 ng/mL) provides reliable evidence that
ovulation has occurred.

35. Is USG monitoring Necessary —
• RCOG and NICE, suggest serial TVS to monitor the number and size of developing follicles and to
time hCG administration if necessary.
• Serial TVS may also provide evidence of ovulation (follicle enlargement followed by collapse
suggests ovulation).
• Some advocate ultrasound monitoring of just the first clomiphene cycle in order to exclude hyper-
response
• However, adding USG monitoring is costly and does not appear to improve pregnancy rates
significantly
• Baseline D2 scan is not always necessary before every new treatment cycle but should be
considered in symptomatic patients.
• Withhold CC in these cases until the cyst(s) disappear either spontaneously or after suppression
with OCP.
Kousta E, White DM, Franks S. Modern use of clomiphene citrate in induction of ovulation. Hum Reprod Update 1997; 3:359.
Vause TD, Cheung AP, Sierra S, et al. Ovulation induction in polycystic ovary syndrome: No. 242, May 2010. Int J Gynaecol Obstet
2010; 111:95.
Smith YR, Randolph JF Jr, Christman GM, et al. Comparison of low-technology and high-technology monitoring of clomiphene citrate
ovulation induction. Fertil Steril 1998; 70:165.

36. OUTCOMES-Ovulatory and pregnancy rates —
 An ovulatory rate of 80% and a cumulative pregnancy rate of 30-40%
can be expected .
Dickey RP, Holtkamp DE. Development, pharmacology and clinical experience with clomiphene citrate. Hum Reprod Update
1996; 2:483.
Gorlitsky GA, Kase NG, Speroff L. Ovulation and pregnancy rates with clomiphene citrate. Obstet Gynecol 1978; 51:265.
Gysler M, March CM, Mishell DR Jr, Bailey EJ. A decade's experience with an individualized clomiphene treatment regimen including
its effect on the postcoital test. Fertil Steril 1982; 37:161.

37. OUTCOMES-Ovulatory and pregnancy rates —
A literature review including data from over 5000 patients with a
variety of indications for clomiphene therapy reported an ovulation
rate of 73%and a pregnancy rate of 36% .
Homburg R. Clomiphene citrate--end of an era? A mini-review. Hum Reprod 2005; 20:2043.

38. OUTCOMES-Ovulatory and pregnancy rates —
 Of those who ovulate, approximately 50% do so at a dose of 50 mg ,
another 20 - 25% at 100 mg, and 10% at 150 mg .
 There is no benefit to increasing the clomiphene dose in subsequent
cycles once ovulation occurs.
Gorlitsky GA, Kase NG, Speroff L. Ovulation and pregnancy rates with clomiphene citrate. Obstet Gynecol 1978; 51:265.
Gysler M, March CM, Mishell DR Jr, Bailey EJ. A decade's experience with an individualized clomiphene treatment regimen
including its effect on the postcoital test. Fertil Steril 1982; 37:161.
Glasier AF. Clomiphene citrate. Baillieres Clin Obstet Gynaecol 1990; 4:491.
Rostami-Hodjegan A, Lennard MS, Tucker GT, Ledger WL. Monitoring plasma concentrations to individualize treatment with
clomiphene citrate. Fertil Steril 2004; 81:1187.

39. Why pregnancy rate is low as compared to
ovulation rate ?
 Clomiphene acts primarily as an antiestrogen in the uterus, cervix,
and vagina.
 The following findings may explain why pregnancy rates are relatively
low when ovulatory rates are so high in women administered
clomiphene cycles:
 The normal increase in uterine volume and endometrial thickening that
occurs during spontaneous menstrual cycles is largely absent during
clomiphene-induced cycles, despite higher estradiol levels .
 Abnormal luteal phase endometrial morphology has been found in some , but
not all , studies.

40. Casper RF, et al. J Clin Endocrinol Metab. 2006; 91: 760-771.
Clomiphene citrate: Anti-estrogenic effects

41. Strategies to prevent thin endometrium
Strategies such as giving half-dose clomiphene (25 mg/day),
early administration (starting day 1), or
adding exogenous estrogen have been tried to minimize the
antiestrogenic effect of clomiphene on the endometrium, with limited
success.

42. Effect on cervical mucus
 Data on the effect of clomiphene on cervical mucus are conflicting.
 While one study found no detrimental effect another noted a decrease in
the quality and quantity of cervical mucus at all clomiphene doses .
 In a meta-analysis, a detrimental effect was seen only with doses ≥100
mg/day .
 Clomiphene citrate has no apparent progestational, corticotropic,
androgenic, or antiandrogenic effects, nor does it interfere with adrenal or
thyroid function.
Thompson LA, Barratt CL, Thornton SJ, et al. The effects of clomiphene citrate and cyclofenil on cervical mucus volume and receptivity
over the periovulatory period. Fertil Steril 1993; 59:125.
Gelety TJ, Buyalos RP. The effect of clomiphene citrate and menopausal gonadotropins on cervical mucus in ovulatory cycles. Fertil Steril
1993; 60:471.

43. OUTCOMES-Ovulatory and pregnancy rates —
The ovulatory rate is lower with increasing age, body mass index
(BMI), insulin resistance, and free androgen index
After six months of treatment, the pregnancy rate per cycle falls
substantially despite regular ovulation
Imani B, Eijkemans MJ, te Velde ER, et al. Predictors of chances to conceive in ovulatory patients during clomiphene citrate
induction of ovulation in normogonadotropic oligoamenorrheic infertility. J Clin Endocrinol Metab 1999; 84:1617.
Macgregor AH, Johnson JE, Bunde CA. Further clinical experience with clomiphene citrate. Fertil Steril 1968; 19:616.

44. OUTCOMES-Ovulatory and pregnancy rates —
• The incidence of miscarriage and congenital anomalies appears to be
similar to that in spontaneous pregnancies, and the rate of ectopic
pregnancy is probably not increased .
• The risk of ovarian hyperstimulation syndrome is less than 1 percent.
Dickey RP, Matis R, Olar TT, et al. The occurrence of ectopic pregnancy with and without clomiphene citrate use in
assisted and nonassisted reproductive technology. J In Vitro Fert Embryo Transf 1989; 6:294.

45. OUTCOMES- Multiple gestation —
• Induction of ovulation by clomiphene increases the probability of
multifetal pregnancy: twins have been reported in 6.9 to 9% of
pregnancies, triplets in 0.3 to 0.5 %, quadruplets in 0.3 %, and
quintuplets in 0.13 % .
• The risk may be reduced by ultrasound monitoring and withholding
human chorionic gonadotropin (hCG), intrauterine insemination (IUI),
or intercourse if more than two follicles >15 mm diameter are seen.
McDowell S, Kroon B, Yazdani A. Clomiphene ovulation induction and higher-order multiple pregnancy. Aust N Z J
Obstet Gynaecol 2013; 53:395.

46. Perinatal outcome —
Most , but not all , studies suggest that the frequencies of congenital
malformations and spontaneous abortion are not increased in
pregnancies after clomiphene therapy.
There is no evidence of developmental delays or learning disabilities
in children whose mothers took clomiphene .
Dickey RP, Taylor SN, Curole DN, et al. Incidence of spontaneous abortion in clomiphene pregnancies. Hum Reprod 1996; 11:2623.
Sørensen HT, Pedersen L, Skriver MV, et al. Use of clomifene during early pregnancy and risk of hypospadias: population based case-
control study. BMJ 2005; 330:126.
Reefhuis J, Honein MA, Schieve LA, et al. Use of clomiphene citrate and birth defects, National Birth Defects Prevention Study, 1997-
2005. Hum Reprod 2011; 26:451.

47. Perinatal outcome — LBW
 Several studies have found a mildly increased risk of preterm birth in pregnancies
(singleton and multiple) after assisted reproduction compared with natural
pregnancies .
 This effect has not been shown to be specific to clomiphene and is likely to be
due, at least in part, to comorbidities in subfertile women rather than the
ovulation stimulation.
 There does not appear to be an increase in cancer risk in children conceived using
ovulation induction drugs.
Lambalk CB, van Hooff M. Natural versus induced twinning and pregnancy outcome: a Dutch nationwide survey of primiparous dizygotic twin
deliveries. Fertil Steril 2001; 75:731.
Källén B, Olausson PO, Nygren KG. Neonatal outcome in pregnancies from ovarian stimulation. Obstet Gynecol 2002; 100:414.
Gaudoin M, Dobbie R, Finlayson A, et al. Ovulation induction/intrauterine insemination in infertile couples is associated with low-birth-weight
infants. Am J Obstet Gynecol 2003; 188:611.

48. Role of modified regimens- Higher doses —
 High-dose clomiphene citrate (200 to 250 mg daily) may be given for
8 to 10 days in women who are refractory to standard doses.
This extended regimen of clomiphene is sometimes used for women
who cannot receive exogenous gonadotropins, but the overall
experience is limited and the dose exceeds current US Food and Drug
Administration (FDA) recommendations.
Use of these high doses is not recommended

49. Adverse effects- Common side effects —
 Hot flashes are common, occurring in 10 to 20 percent of women .
 They may result from hypoestrogenism at the hypothalamic level due
to clomiphene blockade of estrogen receptors.
 Additional problems related to the hyperestrogenic environment
induced by CC include abdominal distention and pain (5.5 percent),
nausea and vomiting (2.2 percent), and breast discomfort (2 percent).
These symptoms abate soon after cessation of therapy.
 Mood swings, depression, and headaches can also occur but are
rarely serious enough to consider terminating treatment.
ACOG Committee on Practice Bulletins-Gynecology. ACOG Practice Bulletin. Clinical management guidelines for obstetrician-
gynecologists number 34, February 2002.
Management of infertility caused by ovulatory dysfunction. American College of Obstetricians and Gynecologists. Obstet
Gynecol 2002; 99:347.

50. Adverse effects- Common side effects —
 Side effects of clomiphene are not dose related, as they can occur at
the 50 mg dose.
Uncomplicated ovarian enlargement develops in approximately 14
percent of women, but true ovarian hyperstimulation syndrome is
rare.

51. Adverse effects-
 Visual disturbances — Visual symptoms, such as blurring, double
vision, and/or scotomata, develop in 1 to 2 percent of women and are
usually reversible.
 However, because they may persist, their onset warrants
discontinuation of therapy .
Purvin VA. Visual disturbance secondary to clomiphene citrate. Arch Ophthalmol 1995; 113:482.
Racette L, Casson PR, Claman P, et al. An investigation of the visual disturbances experienced by patients on
clomiphene citrate. Fertil Steril 2010; 93:1169.

52. Cancer risks —
 The use of clomiphene citrate for ovulation induction does not
appear to be associated with an excess risk of ovarian or breast
cancer.
One retrospective cohort study reported an excess risk of
endometrial cancer with clomiphene, but this has not been
confirmed .
Althuis MD, Moghissi KS, Westhoff CL, et al. Uterine cancer after use of clomiphene citrate to induce ovulation. Am J
Epidemiol 2005; 161:607.
Topic 7400 Version 25.0

53. SUMMARY AND RECOMMENDATIONS-CC
 Clomiphene is initially begun on cycle day 2,3, 4, or 5 at a dose of 50
mg daily for five days.
 If ovulation does not occur in the first cycle of treatment, the dose is
increased to 100 mg.
 Thereafter, the dose is increased by increments of 50 mg to a
maximum daily dose of 150 mg until ovulation is achieved.
 The couple is advised to have intercourse every other day for one
week beginning five days after the last day of medication.
 Most clinicians have their patients use home urinary luteinizing
hormone (LH) kits for monitoring their cycles.

54. SUMMARY AND RECOMMENDATIONS-CC
 A mid-luteal serum progesterone level may be obtained once to document
that clomiphene citrate caused ovulation.
 Serial TVS may also be used, although it increases the cost without having a
significant effect on pregnancy rates.
 Further evaluation or change in therapy is indicated for women who do not
conceive after having six ovulatory cycles.
 Risks and complications should be discussed.
 True ovarian hyperstimulation is rare.
 Clomiphene citrate does not appear to be associated with adverse perinatal
outcomes or an increased risk of congenital malformations.

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

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

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