Pregnancy Complications & Management Related to Polycystic Ovarian Syndrome: An Overview
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International Journal of Research and Review
Vol.8; Issue: 1; January 2021
Website: www.ijrrjournal.com
Review Article E-ISSN: 2349-9788; P-ISSN: 2454-2237
Pregnancy Complications & Management Related to
Polycystic Ovarian Syndrome: An Overview
Chintan Chandrakant Davande1, Ankitsh Ramesh Gade2, Akhil S. Kanekar3
1,2
Final Year B. Pharmacy of Shree Saraswati Institute of Pharmacy, Tondavali, Kankavali, Sindhudurg,
Maharashtra.
Dr. Babasaheb Ambedkar Technological University, Lonere, Raigad, Maharashtra.
3
Assistant Professor in Shree Saraswati Institute of Pharmacy, Tondavali, Kankavali, Sindhudurg, Maharashtra.
Dr. Babasaheb Ambedkar Technological University, Lonere, Raigad, Maharashtra
Corresponding Author: Chintan Chandrakant Davande
ABSTRACT diabetes, pre-eclampsia, Caesar, maternal
complications.
The background of Polycystic Ovary Syndrome
involves majority of studies which shows INTRODUCTION
various complications in pregnancy. These As we know, Female reproductive
studies mainly focused on diagnosis of system (FRS) plays an important role in the
disturbance or abnormalities or imbalance in the human life cycle mainly in first phase of life
menstrual cycle, infertility and hirsutism
cycle which is a birth phase. As the birth
(development of male characteristics) or
chemical imbalance (hyperaldosteronism) in phase starts from pregnancy. Pregnancy is
women’s. This might have attention towards nothing but a " process or sequence of an
pregnancy and child outcomes to achieve better events begins with fertilization, proceed
pregnancy and reduce multiple pregnancies. with implantation, embryonic development
Pregnancy related to Polycystic Ovary and ends with fetal development.” [36]
Syndrome shows or increased risks of various Pregnancy period takes place about 38 to 40
complications. It includes various metabolic weeks after mother's last menstrual cycle.
problems like gestational diabetes, hormonal This pregnancy consists of various stages
problems like hyperaldosteronism and also where fetus can develop. During pregnancy
reproductive problems associated with women period different changes can be occurs in
like miscarriage which able to increased risks in
the females. Stages of fetal development
pregnancy. These complications show long term
effects on those women as well as the delivered starts with fertilization where genetic
offspring. These pregnancy complications material of sperm and secondary oocytes are
further leads to developed risks as metabolic combined to form a single cell mass in
dysfunction as well as reproductive dysfunction uterine tube. [36]
in offspring’s. This topic summarize the After that it gets attached to the
knowledge and facts about Polycystic Ovary walls of endometria. In the 2nd week
Syndrome, complications related to Polycystic embryo is developed with release of hCG
Ovary Syndrome and management of (Human Chorionic Gonadotropin) hormone.
complications related to Polycystic Ovarian At the end of 3rd week primitive organs and
Syndrome which include long term influence on nerve cells are developed. Organogenesis
the women health.
occurred in 4th- 8th week. At last stage
Keywords:- POCS, ovarian cysts, which is a fetal period where brain and other
hyperandrogenism, miscarriage, gestational body parts are fully developed. [36]
International Journal of Research and Review (ijrrjournal.com) 137
Vol.8; Issue: 1; January 2021
Chintan Chandrakant Davande et.al. Pregnancy complications & management related to polycystic ovarian
syndrome: an overview.
Figure 1: Fetal period development[36]
Polycystic Ovary Syndrome:- primary insufficiency. It’s a common
A disorder develops during puberty endocrinal disorder which may include
and characterized by enlargement of ovaries reproductive, endocrine and metabolic
with fluid filled sac (cysts) and tendency to alterations characterized by hypothalamic -
have high levels of male hormone pituitary - ovary axis dysfunction.[24] It is
(androgen). [33] It is also called as STEIN- characterized by Oligominorrhoea,
LEVENTHAL SYNDROME. [39] It is anovulation, hirsutism and obesity in young
chronic anovulation and excess activity women.[30,28]
ovaries that involves ovarian dormancy or
Figure 2: Ovarian Cysts [72]
Epidemiology of PCOS:- Another mechanism involves
It includes chemical abnormalities or unbalanced release of follicle stimulating
chemical imbalance which causes high hormone (FSH) and luteinizing hormone
amount of androgen production, decreasing (LH) leads to inhibition of testosterone but
the production of follicle stimulating level of LH responsible for secretion of
hormone (FSH). This results into swelling androgen inappropriately which cause
of ovaries. [6] anovulation.[79] PCOS can also cause due to
International Journal of Research and Review (ijrrjournal.com) 138
Vol.8; Issue: 1; January 2021
Chintan Chandrakant Davande et.al. Pregnancy complications & management related to polycystic ovarian
syndrome: an overview.
genetic heredity.[61] Ovarian cysts are small age develop small cysts each month. A large
fluid filled sac within ovary during cyst that come problems occurs in about 8%
polycystic ovary syndrome that occurs in women’s before menopause and about 16%
both ovaries. Most women of reproductive after menopause. [79]
Figure 3: Epidemiology of PCOS [32]
Symptoms of PCOS:- Pregnancy Complications related to
1) Trouble in conceiving pregnancy / PCOS :-
Infertility [7] Multiple pregnancy -
2) Mood changes [72] Multiple pregnancies increased
3) Acne [72] complications in prenatal morbidity
4) Fatigue [72] observed in fertility treatment with special
5) Insulin resistance/Diabetic condition [26, regards to women with PCOS affected by an
28, 19]
ovulatory infertility. [114] Most complications
6) High testosterone level [6] are caused due to preterm delivery. [51]
7) Excessive body hair growth [72] Multiple pregnancies are also related to
8) Weight changes and trouble losing obstetric and neonatal complications. Twin
weight [72] pregnancies increased 10 fold risk in
9) Ovarian cysts [72] newborn and 6 fold risk in premature
10) Low sex drive [72] delivery.[92,112] The rates of perinatal
11) Irregular or missed period [72] mortality in the meta - analysis shows
12) Male pattern baldness thinning hair [72] followed difference in multiple pregnancy
rates between women with PCOS and
control Shown in table :
Table 1: Meta-analysis of PCOS[114]
International Journal of Research and Review (ijrrjournal.com) 139
Vol.8; Issue: 1; January 2021
Chintan Chandrakant Davande et.al. Pregnancy complications & management related to polycystic ovarian
syndrome: an overview.
The women with the PCOS had in PCOS women’s. [102,116] Treating the
higher risk of infants delivered preterm GDM which reduces the maternal and
(Risk Ratio = 1.96), very preterm (RR = neonatal complications. [88] The risk of
1.82) and with low birth weight (RR = GDM is three times higher with PCOS
1.39). After adjusting BMI and gestational women’s. [13, 56, 90, 83] The use of metformin
age the difference were no longer reduces the pregnancy complications in 274
statistically. [114, 64] pregnancies of women with PCOS the
showing of PCOS ratio is (17.6 and 16.9 %)
Pregnancy induced hypertension and pre- in the use of metformin and placebo group.
[85, 95, 124]
eclampsia:- Pregnant women with PCOS
Cardiovascular disease occurs 8% of containing GDM ratio is (Odd Ratio 2.32,
PCOS women. The meta-analysis gives 95% Confidence Intervals 1.88 - 2.88).
conclusion of 3- 4 times increase the risk of After adjusting the age, BMI, hypertension,
pregnancy induced hypertension in PCOS smoking, and demographic factor the GDM
pregnancies.[Table1,13,56,90] Higher studies give ratio will be (OR 2.1, 95% CI 1.1- 3.9).
[85,48]
the retrospective design, not the significant The pregnant women with PCOS
effect it’s only detected in the meta having the gestational diabetes mellitus
regression.[90] The PCOS pregnancies lead (GDM) whose baby having the greater risk
to increase the maternal obesity. The meta- of causing the type- 2 diabetes mellitus
analysis gives the result of 3-4 folds later in life.
increase the risk of pre-eclampsia it is
similar to the pregnancy induced Miscarriage :-
hypertension (PIH).[13,56,90] In PCOS Recent studies indicate that PCOS
pregnancies the 50% of women’s cause the women’s are at risk of first trimester
pre-eclampsia as compared to the normal miscarriage. This is because of early
one.[Table 1] In the pre-eclampsia which pregnancy loss (EPL) occurs in 30-50% of
increase the blood pressure after the 20th PCOS women compared with 10-15% of
week of pregnancy. Pre-eclampsia damage normal women’s. [37, 46] Determination of
the mother's organs are kidney, liver, and EPL rate is different in all women’s which
brain. Comparison between PCOS and High cannot be accessed. [99] There are various
Density Proteins (HDP) the risk for mechanisms of EPL which includes obesity,
increased the pre-eclampsia in PCOS insulin resistance, hyperandrogenism,
women but the control group was not Body impaired fibrinolysis and endometrial
Mass Index (BMI) matched.[95] When the dysfunction. [99, 28, 29] Reoccurrence or
comparison between PCOS and non-PCOS spontaneous pregnancy loss in PCOS which
women the higher risk of increase the PIH occurs in nearly 50% of total pregnancies is
in PCOS women after the BMI matched. a frequent obstetric complication. [123,125]
The pre-eclampsia is not treated on time
leads to cause the eclampsia. The PCOS Caesarean Risk :-
pregnancy requires the C-section deliveries, The women with PCOS also lead to
the higher risk for mother as well as baby increase complication in caesarean
i.e. miscarriage, multiple pregnancies etc. deliveries as compared with normal
[114]
deliveries or deliveries of women’s without
PCOS. [42,103] Due to the hormonal in in
Gestational Diabetes Mellitus (GDM):- women with PCOS the size of embryo also
The gestational diabetes is one of the gets increased and hence the risk of C-
diabetes which pregnant women get 40 to section or caesarean delivery gets increased
50% of gestational diabetes complicates the twice as compared to normal women’s. [Table
PCOS pregnancies. [81, 83] GDM caused due 1]
Also other factors like obesity and GDM
to the adequate pancreatic β-cell functioning can increased the risk of caesarean
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Vol.8; Issue: 1; January 2021Chintan Chandrakant Davande et.al. Pregnancy complications & management related to polycystic ovarian
syndrome: an overview.
deliveries. [25,Table 1] The infants with having the women with PCOS. [13,56,38] The
caesarean delivery of women with PCOS meta analysis study report conclude the
can also susceptible towards the risk of large for gestational age ( LGA) and no
shoulder dystocia (condition in which differences found for the outcomes in PCOS
baby’s shoulder get stuck during labor) due and non-PCOS outcomes. [56] The only
to larger size of infant.[117] difference in fetal outcome for the fetal
growth of gestational age neonates is lower
Continuous Preterm Delivery/Prenatal in PCOS then the non-PCOS women ( 68.3
Delivery :- vs. 87.3%) whereas the incidence of SGA
The prenatal deliveries can do worst (15.9 vs. 6.3%). [83, 3]
effect on infant as well as mother with
PCOS compared to mother without PCOS. Offspring health :-
[96]
this can be further leads to GDM, Mother having the PCOS his
obesity and other maternal issues. [49] offspring having higher risk of developing
Prenatal deliveries can indicates adverse endocrine and cardiovascular disease in
effects due to poor development of oocyte, later life and also increase cardio metabolic
embryo quality and intrauterine risk because of the intrauterine environment.
[40] [54, 127, 11]
environment. The prenatal delivery of According to the barker hypothesis
women with PCOS having GDM history the lifetime health can be related to
can leads to develop fetal macrosomia intrauterine environment. [54,11,10,108] PCOS
resistant into altered glucose metabolism women’s offspring having the risk of insulin
and disturbed uterine blood flow. [7] In resistance (IR), metabolic abnormalities,
several studies indicates that increase in endothelial dysfunction, obesity, offspring
preterm delivery (PTD) before 37 weeks of adiposity in later life and develop the first
gestation in PCOS women’s as compared to decade of life.[14,59] The women who having
women’s without PCOS. In women with the pcos whose daughter having little bit
PCOS the risk of PTD with antimullerine problems during the puberty time. If the
hormone (AMH) value is >9.75ng/ml was concentration of dihydroepiandrostenedione
4-fold higher and 2- fold higher in AMH sulphate is increases in the daughter then the
value >13.66ng//ml.[42] onset of puberty and around 30%
exacerbated adrenerche.[71,114] Having the
Other maternal complications :- greater risk of cause ovarian androgenism in
In the PCOS pregnancies the higher adolescence, may it cause pre-pubertal,
risk is the caesarean delivery (OR 1.56, 95% pubertal, and post-pubertal hyper
CI 1.20 - 2.02) i.e. the vaginal delivery was insulinaemia later in life.[24,44,45] Women
quite not higher with the PCOS pregnancies. with pcos whose daughter having higher
[13, 56]
risk of autism spectrum disorders because of
the high testosterone levels.[86,114] It has also
Fetal/neonatal outcomes :- higher risk for the metabolic and
In fetal/neonatal outcomes with the reproductive disorders.[69,108] Pre-pregnancy
women with PCOS having chance to overweight preterm birth and birth weight of
increases the 2- folds risk of preterm singleton newborn compared the overweight
deliveries because of the labor pain of the and normal weight pregnant women with
placental insufficiency. [90] Premature PCOS.[23] The PCOS women gradually
delivery ratio was (OR 2.21, 95% CI 1.69 - increase the baby weight in pregnancy.[83,84]
2.90). [21] The infants who are delivered i.e. the PCOS women are obese in during
prematurely can chance of meconium and after pregnancy. The gestational weight
aspiration (OR 2.02, 95% CI 1.13 - 3.61). gain and obesity are important factor to
[80]
Also the probability to increase 2-fold influencing the offspring health. [22,113] The
risk of small for gestational age (SGA) early metformin treatment can prevent or
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Vol.8; Issue: 1; January 2021Chintan Chandrakant Davande et.al. Pregnancy complications & management related to polycystic ovarian
syndrome: an overview.
delay the development of hirsutism, and sex hormone binding globulin (SHBG)
androgen excess, oligomenorrhoea and pcos concentration in women can significantly
but the initially the metformin treatment in increase or decreased hemodynamic
PCOS with pregnant women has minor changes during development of pulmonary
weight gain pregnancy compared with embolism (PE).[104,105,123,2,33] High level of
controls who received the placebo Gives the androgen can affect the offspring weight,
long term complication in the children disturbance of maternal energy, hemostatic
whose mother having the PCOS.[18,124] and nutrition transport change.[12,109] The
women who conceive pregnancy after long
Pathophysiological considerations time to pregnancy will increased risk of
regarding PCOS pregnancy preterm birth (OR 1.31,95% CI 1.21-
complications :- 1.42).[73,114] Placental alterations causes
Increased pregnancy complications direct effect of androgens on endometria
in women with PCOS having some factor to and dysregulation of lipolysis or lipid
influence chemical as well as biochemical metabolism.[17,52,117]
characteristics of pregnancy outcomes. [114]
This factor is independently playing a major PCOS – related comorbidities :-
role in pathophysiological adverse Obesity is the severe comorbity in
pregnancy outcomes in women with PCOS. the reproduction associated with
[62,117,77]
PCOS. Obesity increased the risk of
Relevance of the heterogeneous PCOS miscarriage and also other risks of maternal
features :- complications like thromboembolism.[74,57]
Hyperandrogenism ovarian The women’s with PCOS associated with
dysfunction with related oligo-amenorrhoea visceral obesity increased 2-3 fold risk of
and polycystic ovary morphology (PCOM) PIH and PE which associated with the body
are main criteria for the diagnosis of fat.[101,119,1] Obese PCOS women also
PCOS.[58,60,97] In PCOS women’s androgen increased a risk of unplanned caesarean
level are higher in compared with the non- delivery.[9,27,124,129] Fetus of obese PCOS
PCOS controls it increases throughout the women having risks of neural tube defects ,
pregnancy hyperandrogenism causes the heart defects and omphalocele.[106,16,93] It
pregnancy.[68,110,53,33] The hyperandrogenism also shows long-term effects on metabolic
or increased androgen synthesis during disorder like hyperinsulinaemia associated
pregnancy in women with PCOS are an with IR which develops hypertensive
abnormal steroidogenic function of the disorders in pregnancy.[26,75] Women with
placenta in women with PCOS was PIH/PE elevates insulin level and cause
demonstrated.[31,70,118] Serum testosterone uncomplicated pregnancy. [63]
Figure 4: Schematic Representation of Pathological Complications [5]
International Journal of Research and Review (ijrrjournal.com) 142
Vol.8; Issue: 1; January 2021Chintan Chandrakant Davande et.al. Pregnancy complications & management related to polycystic ovarian
syndrome: an overview.
PCOS- related infertility interventions :- low molecular weight heparin (LMWH)
The anovulatory infertility can also reduce pregnancy loss in
leads to increased risk in complications hyperhomocysteinaemia without any
related to PCOS pregnancy.[43,94] The maternal side effect. [91, 19, 20]
pregnancies conceive and achieved after a
time to pregnancy of more than 12 months Prevention and management in PCOS :-
probably ends premature delivery and infant There is no proper prevention to
having lower weight.[73] In obese women avoid PCOS syndrome but the PCOS
with PCOS consists a combination of women can get proper nutrition and weight
hypocaloric diet and increased physical management to avoid a complications such
activity required for losing weight. This as diabetes, PIH and other cardiovascular
results into increase natural reproductive diseases. [114] In the PCOS pregnancies the
outcomes.[67,82] PCOS women having higher IR to cause the metabolic alteration as
risk of preterm delivery due to ovulatory compared to normal pregnancies. In PCOS
induction as compared to women without pregnant obese women having greater risk
PCOS conceiving pregnancy (OR 1.45 95% of preterm/neonatal delivery, intrauterine
CI 1.21-1.74).[87] IR is a typical death and berth trauma as well as having
characteristic of women with PCOS with greater risk of GDM and PE (RR 0.74, 95%
prevalence ranging from 75-95% with CI 0.60-0.92) if it is avoid follow the dietary
respect to BMI in case of insulin sensitive schedule to maintain the weight gain in
biguanides particularly metformin on pregnancy. [120] Before the conception
ovulatory induction.[114,115] Gonadotropins developing higher risk of GDM in PCOS
mediated ovulation induction indicated women depends on the fasting glucose
resistance or failure with clomiphene level, androstindione, SHBG concentration
citrate.[121] and post history of type 2 diabetes. [114] In
non-PCOS women related risk obesity,
Hormone Independent alterations in higher age, and particular ethnicity. The
Placenta :- cholesterol, triglycerides, high density
Hormone independent alterations are lipoprotein (HDL), B.P. and glucose level
an important pathway in a nutrients are confirmed before in pregnancies because
transport of placenta for fetal growth in there imbalance caused the preterm birth
human with PCOS. [120] Effect of weight and shorter the gestational period. [66] In
loss during pregnancy in obese women has a gestational period to maintain hygiene and
limited data.[35] According to data 2.9% of total focus on the early change of proteins
women’s of reproductive age affected by leads to dyslipidemia and to decrease
pregestational diabetes specially type two hemoglobin level and hematocrit level
diabetes mellitus.[41,4] Preconception care because of these biochemical markers
aimed at ensuring an adequate glycemic causes the higher risk of pregnancy
control which reduces risk of GDM. [122] In complication in women with PCOS. [114]
a case of women with PCOS associated with Metformin is antidiabetic drug which is
GDM metformin is an effective and safe as used in the GDM. [98] It helps to maintain
a medication, particularly for overweight blood glucose level safely and effectively in
and obese women.[8] Potential use of the patient with GDM in non RCTs. [128,
78,130]
metformin over insulin suggested because In randomized controlled trials (RCTs)
maternal weight gaining pregnancy patient repeatedly use of metformin causes the
compliance an infant health.[97,58,111] decrease in maternal weight gains in
Administration of metformin in pregnant pregnancy it also caused the uterine artery
women reduces uterine artery impedance impedance in between the 12 to 19 weeks
between 12-19 weeks of gestation gestational period. [36] Hence, it does not
period.[100] Combinations of metformin with show specific effect to reduce or prevent
International Journal of Research and Review (ijrrjournal.com) 143
Vol.8; Issue: 1; January 2021Chintan Chandrakant Davande et.al. Pregnancy complications & management related to polycystic ovarian
syndrome: an overview.
PIH. Metformin is combine with LMWH to hypoglycemic agent in the PCOS
decrease pregnancy loss in limited women’s women.[128,78] There is no evidence that
associated with PCOS. As LMWH is metformin reduces BMI in women with
prescribed alone to reduce pregnancy loss as PCOS compared with placebo.[78] The
well as coagulation. LMWH and women who receive antiandrogens along
Acetylsalicylic Acid (ASA) are combined to with oral contraceptives will minimize the
avoid spontaneous abortion in those women effect of metformin on BMI.[65] Liraglutyl is
with hyperhomocystenemia.[19,20,85] a glucagon like peptide receptor-1 agonist
Combination of oral contraceptives and use for the treatment of type-2 diabetes and
anti-androgens reduce androgen level which obesity which significantly helps in weight
helps to treat symptomatic endometrial loss and reduces waist circumstance.[47]
problems.[69] Overall goals of therapy Myo-and D-chiro-inositol is insulin
include severity of hyperandrogenic sensitizing agent works as an insulin
syndrome reduction of risk factors for GDM singling secondary messenger and also as a
and cardiovascular disease and metabolic possible alternative to metformin in IR
abnormalities management, planning to associated PCOS women.[76]
obtain safe pregnancy by improving quality
of life achieved by multidisciplinary team Quality of life: - PCOS patient having large
providing patient center care.[Figure.5] impact of psychological effect like
depression, anxiety, and sleep disorders. [21]
Metabolism:- Overweight and obese Psychological effect includes common
patient, weight loss is caused due to change symptoms like sleep disturbance, appetite
in physical activity and nutritional alteration change, fatigue and loss in interest in daily
which leads to decrease insulin and activities. Evolution of these is essential for
androgen level results into glucose better care and management for those
intolerance.[7] Metformin is commonly used patient associated with PCOS. [Figure.5]
drug which act as an insulin sensitizing and
Figure 5: Objectives of assessing the quality of life [5]
Infertility: - associated with infertility and anovulation.
First line therapy includes folic acid Metformin is not recommended in ovulation
supplement and cessation of smoking and induction due to low live birth rate. [78, 89]
alcohol consumption. Second line treatment Letrozole which is an aromatase inhibiter
includes ovulation induction. Clomiphene work as alternative to clomiphene citrate.
[126, 34]
citrate is given as a reference therapy for
ovulation induction in women with PCOS
International Journal of Research and Review (ijrrjournal.com) 144
Vol.8; Issue: 1; January 2021Chintan Chandrakant Davande et.al. Pregnancy complications & management related to polycystic ovarian
syndrome: an overview.
Patient Counselling with Psychological polycystic ovary syndrome involved various
support:- clinical, biochemical and proteomic markers
As we know, PCOS is a hormonal as a potential diagnostic tool. Other things
imbalance disorder which mainly affect at a involved in the PCOS pregnancy are
gestational period of a women. So, to avoid reproductive history including non-
or handle any complications regarding complicated and complicated pregnancies
PCOS in pregnant women as well as in which cause long-term maternal and
infant preconception counselling or advice offspring health effects. Pregnancy
regarding lifestyle, obesity and period of complications in PCOS include long term
conceiving pregnancy should be required.[44] maternal effects like ovarian
Most of the study indicates that women with steroidogenesis, development of type-2
PCOS associated with obesity or weight diabetes mellitus, PE, cardiovascular
gain affected most by the metabolic, disease. PCOS can also able to cause some
psychological and reproductive repercussion phenotypic alterations. Integral management
of PCOS.[90] PCOS women have low rate of regarding to PCOS need to develop a
pregnancy due to lower uptake of multidisciplinary team which helps to
contraception and hence practitioner should provide lifestyle interventions and
counseled patient about appropriate use of psychological support to patient. Some of
contraception to avoid unplanned the complications are explored but most of
[43]
pregnancy. In women with PCOS the complications remain unexplored. To
requires more psychological support like explore this complications and treatment
interpersonal communication, emotional as regarding to polycystic ovary syndrome is
well as relational support.[50,55] The important future perspective for research.
counselling should include things like
exercise and nutritional counselling on ACKNOWLEDGEMENT
hormonal, menstrual and reproductive To the best of our knowledge, the
function in women with PCOS.[15] material included in this topic is having
original sources which are appropriately
CONCLUSION acknowledged and referred. We would like
As pregnancy is an important event to express our sincere gratitude to our
of women’s life cycle. This topic highlights professor Mr. Akhil Kanekar for his
about major complications and management continuous guidance, support and
to avoid or handle complications related to motivation. We would also like to thank
women associated with polycystic ovarian library staffs.
syndrome. As the mechanism for PCOS is
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