Infertility in polycystic ovary syndrome
Encyclopedia
Polycystic ovary disease (PCOS) is thought to be one of the leading causes of female infertility
Female infertility
-Causes and factors:Causes or factors of female infertility can basically be classified regarding whether they are acquired or genetic, or strictly by location.-Acquired versus genetic:...

. Polycystic ovary syndrome is the cause of more than 75% of cases of anovulatory infertility.

Pathophysiology

Not all women with PCOS have difficulty becoming pregnant. For those who do, anovulation
Anovulation
An anovulatory cycle is a menstrual cycle during which the ovaries do not release an oocyte. Therefore, ovulation does not take place. However, a woman who does not ovulate at each menstrual cycle is not necessarily going through menopause...

 is a common cause. The mechanism
of this anovulation, is uncertain, but there is evidence of arrested antral follicle
Antral follicle
An antral follicle is an ovarian follicle during a certain latter stage of folliculogenesis.Definitions differ in where the shift into an antral follicle occurs in the staging of folliculogenesis, with some stating that it occurs when entering the secondary stage, and others stating that it occurs...

 development, which, in, turn, may be caused by abnormal interaction of insulin and luteinizing hormone
Luteinizing hormone
Luteinizing hormone is a hormone produced by the anterior pituitary gland. In females, an acute rise of LH called the LH surge triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell-stimulating hormone , it stimulates Leydig cell...

 (LH) on granulosa cells.

Endocrine disruption may also directly decrease fertility, such as changed levels of gonadotropin-releasing hormone
Gonadotropin-releasing hormone
Gonadotropin-releasing hormone , also known as Luteinizing-hormone-releasing hormone and luliberin, is a tropic peptide hormone responsible for the release of follicle-stimulating hormone and luteinizing hormone from the anterior pituitary. GnRH is synthesized and released from neurons within...

, gonadotrophins (especially an increase in luteinizing hormone
Luteinizing hormone
Luteinizing hormone is a hormone produced by the anterior pituitary gland. In females, an acute rise of LH called the LH surge triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell-stimulating hormone , it stimulates Leydig cell...

), hyperandrogenemia and hyperinsulinemia
Hyperinsulinemia
Hyperinsulinemia, or hyperinsulinaemiais a condition which there is excess levels of insulin circulating in the blood than expected relative to the level of glucose. While it is often mistaken for diabetes or hypoglycaemia, hyperinsulinemia can result from a variety of metabolic diseases and...

. Gonadotrophins are released by gonadotroph cells in pituary gland, and these cells appear to harbor insulin receptors, which are affected by too high insulin levels in body. 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 will reduce the overstimulation of gonadotroph cells in pituitary.

Diagnosis

PCOS usually causes infertility associated with anovulation, and therefore, the presence of ovulation indicates absence of infertility, although it does not rule out infertility by other causes.

Ovulation prediction

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. 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.

While not useful for predicting ovulation, basal body temperature
Basal body temperature
Basal body temperature is the lowest temperature attained by the body during rest . It is generally measured immediately after awakening and before any physical activity has been undertaken, although the temperature measured at that time is somewhat higher than the true basal body temperature...

s may be used to confirm ovulation. Ovulation may also be confirmed by testing for serum progesterone
Progesterone
Progesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...

 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 day 21). A mid-luteal phase progesterone test may also be used to diagnose luteal phase
Luteal phase
The luteal phase is the latter phase of the menstrual cycle or the estrous cycle . It begins with the formation of the corpus luteum and ends in either pregnancy or luteolysis...

 defect. Methods that confirm ovulation may be used to evaluate the effectiveness of treatments to stimulate ovulation.

Management

Management of infertility in polycystic ovary syndrome includes lifestyle modification as well as assisted reproductive technology
Assisted reproductive technology
Assisted reproductive technology is a general term referring to methods used to achieve pregnancy by artificial or partially artificial means. It is reproductive technology used primarily in infertility treatments. Some forms of ART are also used in fertile couples for genetic reasons...

 such as ovulation induction, oocyte release triggering and surgery.

Lifestyle modification

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

Ovulation induction

For those who after weightloss still are anovulatory or for anovulatory lean women, ovulation induction
Ovulation induction
Ovulation induction is the stimulation of ovulation by medication. It is usually used in the sense of stimulation of the development of ovarian follicles to reverse anovulation or oligoovulation, but can also be used in the sense of triggering oocyte release from relatively mature ovarian follicles...

 to reverse the anovulation is the principal treatment used to help infertility in PCOS. Clomiphene citrate is the main medication used for this purpose.

In vitro fertilization

For patients who do not respond to diet, lifestyle modification and clomiphene, in vitro fertilisation
In vitro fertilisation
In vitro fertilisation is a process by which egg cells are fertilised by sperm outside the body: in vitro. IVF is a major treatment in infertility when other methods of assisted reproductive technology have failed...

 can be performed. This usually includes controlled ovarian hyperstimulation with FSH
Follicle-stimulating hormone
Follicle-stimulating hormone is a hormone found in humans and other animals. It is synthesized and secreted by gonadotrophs of the anterior pituitary gland. FSH regulates the development, growth, pubertal maturation, and reproductive processes of the body. FSH and Luteinizing hormone act...

 injections, and oocyte release triggering with human chorionic gonadotropin
Human chorionic gonadotropin
Human chorionic gonadotropin or human chorionic gonadotrophin is a glycoprotein hormone produced during pregnancy that is made by the developing embryo after conception and later by the syncytiotrophoblast .. Some tumors make this hormone; measured elevated levels when the patient is not...

 (hCG) or a GnRH agonist.

Surgery

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
FSH
FSH may refer to:* Follicle-stimulating hormone* Fox Sports Houston, a regional Fox Sports Net affiliate station for the Houston, Texas area* Facioscapulohumeral muscular dystrophy* International Civil Aviation Organisation code for Flash Airlines...

.

Inefficacy of metformin

Previously, metformin was recommended treatment for anovulation. But in the largest trial to date, comparing clomiphene with metformin, clomiphene was more effective than metformin alone. In this trial, 626 women were randomized to three groups: metformin alone, clomiphene alone, or both. The live-birth rates following 6 months of treatment were 7.2% (metformin), 22.5% (clomiphene), and 26.8% (both). The major complication of clomiphene was multiple pregnancy, affecting 0%, 6% and 3.1% of women respectively. The overall success rates for live birth remained disappointing, even in women receiving combined therapy, but it is important to consider that the women in this trial had already been attempting to conceive for an average of 3.5 years, and over half had received previous treatment for infertility. Thus, these were women with significant fertility problems, and the live-birth rates are probably not representative of the typical PCOS woman. Following this study, the ESHRE/ASRM-sponsored Consensus workshop do not recommend metformin for ovulation stimulation. Subsequent randomized studies have confirmed the lack of evidence for adding metformin to clomiphene.
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