Infertility in polycystic ovary syndrome

Polycystic ovary disease (PCOS) is a hormonal imbalance in women that is thought to be one of the leading
causes of female infertility.[1][2][3][4] Polycystic ovary
syndrome causes more than 75% of cases of anovulatory
infertility.[5]

chances of conceiving it is best to have intercourse at least

every other day during the 2nd and 3rd week after their
period ends.

Endocrine disruption may also directly decrease fertility, such as changed levels of gonadotropin-releasing
hormone,[6] gonadotropins (especially an increase in
luteinizing hormone),[6][7] hyperandrogenemia,[8] and
hyperinsulinemia.[8] Gonadotropins are released by gonadotroph cells in pituary gland, and these cells appear to
harbor insulin receptors, which are aected by elevated
insulin levels.[6] A reason that insulin sensitizers work in
increasing fertility is that they lower total insulin levels
in body as metabolic tissues regain sensitivity to the hormone. This reduces the overstimulation of gonadotroph
cells in pituitary.[6]

3 Management

Ovulation may also be conrmed by testing for serum

progesterone in mid-luteal phase, approximately seven
days after ovulation (if ovulation occurred on the average cycle day of fourteen, seven days later would be cycle
1 Pathophysiology
day 21). A mid-luteal phase progesterone test may also be
used to diagnose luteal phase defect. Methods that conrm
ovulation may be used to evaluate the eectiveness
Not all women with PCOS have diculty becoming pregof
treatments
to stimulate ovulation.
nant. For those who do, anovulation is a common cause.
The mechanism of this anovulation is uncertain, but there Basal body temperatures are not reliable for predicting
is evidence of arrested antral follicle development, which, ovulation.[10]
in turn, may be caused by abnormal interaction of insulin
and luteinizing hormone (LH) on granulosa cells.[5]

Management of infertility in polycystic ovary syndrome

includes lifestyle modication as well as assisted reproductive technology such as ovulation induction, oocyte
release triggering and surgery.

3.1 Lifestyle modication

For overweight women with PCOS who are anovulatory,
diet adjustments and weight loss are associated with resumption of spontaneous ovulation.

Diagnosis

One of the best ways to regulate your body and possibly

reverse PCOS is through exercise. Even small amounts
have been shown to make a big dierence. Any form of
PCOS usually causes infertility associated with anovulaexercise will help increase the chances of regularity and
tion, and therefore, the presence of ovulation indicates
possibly ovulation.
absence of infertility, though it does not rule out infertility by other causes.

3.2 Ovulation induction

2.1

Ovulation prediction

For those who after weightloss still are anovulatory or

for anovulatory lean women, ovulation induction to reverse the anovulation is the principal treatment used
to help infertility in PCOS. Clomiphene citrate is the
main medication used for this purpose, and is the rstline treatment in subfertile anovulatory patients with
PCOS.[11] Gonadotrophins such as follicle-stimulating
hormone (FSH) are, in addition to surgery, second-line
treatments.[11]

Ovulation may be predicted by the use of urine tests that

detect the preovulatory LH surge, called ovulation predictor kits (OPKs). However, OPKs are not always accurate when testing on women with PCOS.[9] Charting
of cervical mucus may also be used to predict ovulation, or certain fertility monitors (those that track urinary
hormones or changes in saliva) may be used. Methods
that predict ovulation may be used to time intercourse
or insemination appropriately. Women with PCOS of- Aromatase inhibitors show promising results.[11] A
ten ovulate at any time during their cycle, to best increase Cochrane review came to the results that the aromatase
1

REFERENCES

inhibitor letrozole appears to improve live birth and preg- ical pregnancy rates. However, the risk of ovarian hypernancy rates compared to clomiphene citrate.[12] There ap- stimulation syndrome (OHSS) in women with PCOS and
peared to be no dierence between letrozole and laparo- undergoing IVF cycles is reduced with metformin.[17]
scopic ovarian drilling.[12]

3.3

In vitro fertilization

4 Prognosis

For patients who do not respond to diet, lifestyle modi- PCOS increases the time to pregnancy but does not nec[11]
cation and clomiphene, in vitro fertilisation can be per- essarily reduce eventual family size. It does not appear
[11]
formed. This usually includes controlled ovarian hyper- to increase miscarriage frequency.
stimulation with FSH injections, and oocyte release triggering with human chorionic gonadotropin (hCG) or a
GnRH agonist.
5 References

3.4

Surgery

Surgery can be attempted in case of inecient result with

medications for ovulation induction.[11] Though surgery
is not commonly performed, the polycystic ovaries can
be treated with a laparoscopic procedure called ovarian
drilling (puncture of 4-10 small follicles with electrocautery), which often results in either resumption of spontaneous ovulations or ovulations after adjuvant treatment
with clomiphene or FSH.

3.5

Inecacy of metformin

Previously, metformin was recommended treatment for

anovulation.
A systematic review and meta-analysis in 2012[13] concluded that there is insucient evidence to establish a
dierence between metformin and clomiphene citrate
in terms of ovulation, pregnancy, live birth, miscarriage, and multiple pregnancy rates in women with PCOS
and a BMI less than 32 kg/m2 .[13] It emphasized that a
lack of superiority of one treatment is not evidence for
equivalence.[13]
Another review in 2012[14] concluded that metformin improves pregnancy rates in women with PCOS when compared with placebo, and in addition to clomiphene compared with clomiphene alone, but not when compared directly with clomiphene. Also, however, it concluded that
metformin does not improve live birth rates, whether used
alone or in combination with clomiphene. It therefore
concluded that the benet of metformin in the improvement of reproductive outcomes in women with PCOS is
limited.[14]
The ESHRE/ASRM-sponsored Consensus workshop does not recommend metformin for ovulation
stimulation.[15] Subsequent randomized studies have
conrmed the lack of evidence for adding metformin to
clomiphene.[16]

[1] Goldenberg N, Glueck C (2008). Medical therapy in

women with polycystic ovary syndrome before and during
pregnancy and lactation. Minerva Ginecol 60 (1): 6375.
PMID 18277353.
[2] Boomsma CM, Fauser BC, Macklon NS (2008). Pregnancy complications in women with polycystic ovary
syndrome. Semin. Reprod. Med. 26 (1): 7284.
doi:10.1055/s-2007-992927. PMID 18181085.
[3] Palacio JR et,al.The presence of antibodies to oxidative modied proteins in serum from polycystic
ovary syndrome patients Clin Exp Immunol. 2006
May;144(2):217-22.PMID 16634794
[4] Azziz R. et.al.The prevalence and features of the polycystic ovary syndrome in an unselected population. J
Clin Endocrinol Metab. 2004 Jun;89(6):2745-9. PMID
15181052
[5] Gorry, A.; White, D. M.; Franks, S. (August 2006).
Infertility in polycystic ovary syndrome: focus on lowdose gonadotropin treatment. Endocrine 30 (1): 2733.
doi:10.1385/ENDO:30:1:27. PMID 17185789.
[6] Brothers, K. J.; Wu, S.; Divall, S. A.; Messmer, M. R.;
Kahn, C. R.; Miller, R. S.; Radovick, S.; Wondisford, F.
E.; Wolfe, A. (2010). Rescue of Obesity-Induced Infertility in Female Mice due to a Pituitary-Specic Knockout of the Insulin Receptor (IR)". Cell Metabolism 12
(3): 295305. doi:10.1016/j.cmet.2010.06.010. PMC
2935812. PMID 20816095.
[7] Deepak A. Rao; Le, Tao; Bhushan, Vikas (2007). First
Aid for the USMLE Step 1 2008 (First Aid for the Usmle
Step 1). McGraw-Hill Medical. ISBN 0-07-149868-0.
[8] Qiao, J.; Feng, H. L. (2010). Extra- and intraovarian factors in polycystic ovary syndrome: impact
on oocyte maturation and embryo developmental competence. Human Reproduction Update 17 (1): 1733.
doi:10.1093/humupd/dmq032. PMC 3001338. PMID
20639519.
[9] Question about opks with pcos. Retrieved 7 May 2010.

When taken prior to or during IVF, there is no evidence [10] Basal Body Temperature. Pacic Fertility Center. Rethat metformin treatment improves live birth rate or clintrieved 6 March 2015.

[11] Baird, D. T.; Balen, A.; Escobar-Morreale, H. F.; Evers, J. L. H.; Fauser, B. C. J. M.; Franks, S.; Glasier,
A.; Homburg, R.; La Vecchia, C.; Devroey, P.; Diedrich,
K.; Fraser, L.; Gianaroli, L.; Liebaers, I.; Sunde, A.;
Tapanainen, J. S.; Tarlatzis, B.; Van Steirteghem, A.;
Veiga, A.; Crosignani, P. G.; Evers, J. L. H. (2012).
Health and fertility in World Health Organization group
2 anovulatory women. Human Reproduction Update 18
(5): 586599. doi:10.1093/humupd/dms019. PMID
22611175.
[12] Franik, Sebastian;
Kremer, Jan AM; Nelen,
Willianne LDM; Farquhar, Cindy; Franik, Sebastian (2014).
Aromatase inhibitors for subfertile women with polycystic ovary syndrome.
doi:10.1002/14651858.CD010287.pub2.
[13] Misso, M. L.; Costello, M. F.; Garrubba, M.; Wong,
J.; Hart, R.; Rombauts, L.; Melder, A. M.; Norman, R.
J.; Teede, H. J. (2012). Metformin versus clomiphene
citrate for infertility in non-obese women with polycystic ovary syndrome: A systematic review and metaanalysis. Human Reproduction Update 19 (1): 211.
doi:10.1093/humupd/dms036. PMID 22956412.
[14] Tang, T.; Balen, A. H. (2012). Use of metformin for
women with polycystic ovary syndrome. Human Reproduction Update 19 (1): 1. doi:10.1093/humupd/dms040.
PMID 23114640.
[15] Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group (March 2008).
Consensus on infertility treatment related to polycystic ovary
syndrome.
Fertil.
Steril.
89 (3): 50522.
doi:10.1016/j.fertnstert.2007.09.041. PMID 18243179.
[16] Johnson NP, Stewart AW, Falkiner J et al. (April
2010). PCOSMIC: a multi-centre randomized trial in
women with PolyCystic Ovary Syndrome evaluating Metformin for Infertility with Clomiphene. Hum Reprod
25 (7): 167583. doi:10.1093/humrep/deq100. PMID
20435692.
[17] Farquhar, C.; Rishworth, J. R.; Brown, J.; Nelen,
W. L. M.; Marjoribanks, J. (2013). Brown, Julie,
ed. Assisted reproductive technology: an overview
of Cochrane Reviews.
The Cochrane Library 8:
CD010537.
doi:10.1002/14651858.CD010537.pub2.
PMID 23970457.

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