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Ovulation Induction

Ovulation induction is an artificial reproductive technique (ART) that uses hormonal therapy to initiate the development and release of an egg for fertilisation. It is often used to stimulate the maturation of multiple eggs in a single menstrual cycle, thereby increasing the chances of fertilisation.

Condition

Every woman is born with a lifetime’s supply of egg cells in her ovaries. Each egg cell is contained in a small sac called a follicle. Follicle stimulating hormone (FSH) and luteinising hormones (LH) are two hormones produced by the brain to stimulate and regulate the monthly release of an egg. At the onset of puberty, one egg from an ovary is released every month until menopause (cessation of periods). Each egg released is picked up by the adjacent fallopian tube. The egg can be fertilised by a sperm and lead to pregnancy or, in the absence of sperm, it will dissolve and be flushed out with the menstrual flow. Each stage of ovulation is governed by many hormones secreted by the hypothalamus, pituitary gland, adrenal gland, thyroid gland and ovaries.

This process of ovulation and its timing within the menstrual cycle plays a key role in determining fertility and achieving pregnancy. A normal menstrual cycle is between 28-32 days, measured from the first day of period to the first day of the next menstrual flow. Some cycles may be shorter or longer. Ovulation usually occurs on the 11th to 21st day, starting from the first day of the last menstrual period (LMP). This is considered a fertile period when couples wishing to conceive can have intercourse and increase their chances of pregnancy.

When you visit your doctor with problems in your menstrual cycle or inability to attain a pregnancy despite trying without contraception for a year, your doctor will review your menstrual history and perform a thorough physical examination. You may be asked to record your daily body temperature as an increase in your body temperature indicates ovulation. This can also be performed using a home ovulation predictor kit. Other tests may include ultrasound or blood tests.
Being the most common ovulation disorder that causes infertility, PCOS affects 5-10% women of childbearing age.
Ovulation disorders disrupt or prevent the ovulation process and can thereby lead to infertility. It is a cause of infertility when associated with irregular or no periods (amenorrhea). It is rarely a cause of infertility when associated with regular menstrual periods without premenstrual symptoms, such as mood swings, breast tenderness or lower abdominal swelling.
Eggs are contained in two small oval-shaped ovaries present on either side of the womb in the pelvic region. At the time of ovulation, one mature egg is released from the ovary and picked up by finger-like structures at the ends of the fallopian tube. The tube then transports the egg to the womb.

Ovulation disorders occur when one part of the ovulation process malfunctions. This can happen when:

  • The hypothalamus stops secreting gonadotropin-releasing hormone, which signals the pituitary gland to release LH and FSH, the two hormones that trigger ovulation.
  • The pituitary gland produces low levels of LH and FSH.
  • The pituitary gland produces high levels of prolactin, which results in low levels of hormones that stimulate ovulation. This may be caused because of a pituitary gland tumour.
  • The ovaries release low levels of oestrogen hormone.
  • The adrenal glands release high levels of male hormones (such as testosterone).
  • The thyroid glands release very high or very low levels of thyroid hormones, which regulates the pituitary gland and ovaries.

Ovulation problems may occur as a result of a disorder such as

  • Polycystic ovary syndrome (PCOS)
  • Diabetes
  • Early menopause

You may be at a risk for ovulation problems if you have the following:

  • Obese
  • Psychological stress
  • Are on certain drugs (such as estrogens, progestins and antidepressants)
  • Excessive exercise
  • Weight loss

The signs and symptoms of ovulation problems depend on the related disorder and may include:

  • Absent or irregular periods
  • Unusual spotting, light or heavy periods
  • Pain during periods and intercourse
  • Lack of premenstrual symptoms such as bloating or breast tenderness
  • Pelvic pain
  • Acne, excessive growth of facial hair
  • Obesity
Ovulation induction is associated with PCOS, diabetes and infertility.
When you visit your doctor with problems in your menstrual cycle or inability to attain a pregnancy despite trying without contraception for a year, your doctor will review your menstrual history and perform a thorough physical examination. You may be asked to record your daily body temperature as an increase in your body temperature indicates ovulation. This can also be performed using a home ovulation predictor kit. Other tests may include ultrasound or blood tests.

Treatment

What are the consequences of not treating ovulation disorder?
Left untreated, you may not be able to have biological offspring.

Ovulation problems can be treated with lifestyle changes such as diet and maintaining a healthy weight. Other treatments may include:

  • Fertility drugs
  • In vitro fertilisation
  • Surgery to open blocked fallopian tubes and remove endometrial tissue

You will be considered for ovulation induction if you suffer from:

  • Anovulation: absence of ovulation (ovaries do not release an egg)
  • Oligo-ovulation: irregular ovulation
  • PCOS
  • Luteal phase deficiency (LPD): insufficient production of progesterone
  • Unexplained infertility
  • During IVF, to trigger ovulation for the treatment of male factor infertility
  • During IVF, to increase the number of eggs released

The required prerequisites for ovulation induction are:

  • Healthy fallopian tubes that are open and not blocked.
  • Absence of moderate/severe endometriosis, especially involving the tubes and/or the ovaries, and pelvic inflammatory disease
  • Fertile sperm test
  • Adequate ovarian reserve

Before ovulation induction, your doctor will suggest:

  • Semen analysis to test for sperm count and number and presence of sperm antibody to exclude male infertility
  • Hysterosalpingogram (HSG) or laparoscopy, to test the viability of fallopian tubes

Ovulation induction involves the following steps:

  • Ovulation stimulation: This involves the administration of certain drugs to initiate the release of egg(s) from your ovary. The following are commonly used drugs for ovulation induction:
    • Clomiphene citrate: oral medication that is administered on the 3rd to 5th day after the onset of your periods. This drug works by blocking oestrogen receptors, making your body believe that the levels of oestrogen are low. The body thus initiates the production FSH and induces ovulation. This method of treatment requires monitoring.
    • Human menopausal gonadotropin (hMG): injectable medication that includes FSH and LH that is administered early in the menstrual cycle and continued for 8 to 14 days until the maturation of one or more follicles.
    • Follicle stimulating hormone (FSH): daily injectable medication administered for 5 to 12 days until the maturation of one or more follicles.
    • Synthetic gonadotropin releasing hormone (FSH/LH inhibitor): causes an initial surge of LH and FSH followed by the suppression of these hormones. It is used in preparation for ovulation induction cycles as it improves hormonal control, enhances egg production and prevents spontaneous ovulation.
  • Cycle monitoring: Throughout your treatment, your doctor will monitor how you respond to treatment through blood tests. This helps your doctor change the treatment if needed. Vaginal ultrasound may be ordered to check the number and size of the follicles. You will not be restricted from intercourse during this period.
  • Ovulation: Once the follicles mature, your doctor will inject human chorionic gonadotropin (hCG) to trigger the release of the egg from the follicle, which happens within 36 hours. Two things can happen during this time:
    • You will be advised on the appropriate time to have intercourse.
    • Your doctor will perform an intrauterine insemination as part of the IVF procedure, where sperm will be directly inserted into your uterus for fertilisation.
  • Luteal phase: Approximately 10 days after your hCG injection, you are required to confirm ovulation through a blood test. If your menstrual flow does not start, you are required to perform a pregnancy test after 16 days of your injection.

After confirming positive for pregnancy, your doctor will continue to monitor the progress of your pregnancy with weekly hCG tests for about 8 weeks of pregnancy. Then, an ultrasound is performed to determine the presence of a pregnancy sac with a foetus and the presence of a foetal heartbeat.

After confirming positive for pregnancy, your doctor will continue to monitor the progress of your pregnancy with weekly hCG tests for about 8 weeks of pregnancy. Then, an ultrasound is performed to determine the presence of a pregnancy sac with a foetus and the presence of a foetal heartbeat.

Ovulation induction helps release a healthy egg for fertilisation or multiple eggs for IVF treatment.

Some of the potential risks of ovulation induction are

  • Multiple gestation
  • Ovarian hyperstimulation
  • Increased time commitment
Ovulation induction starts on the third day of your menstrual cycle for about 7 to 10 days. This may continue for a few cycles until you achieve pregnancy. However, this does not require you to be off work. You can go about your normal routine.
Any costs involved will be discussed with you prior to your surgery.
Not all forms of ovulation disorders can be prevented. However, maintaining a normal weight can lower your risk of ovulation disorders.

Eating healthy and engaging in moderate exercise are recommended for managing ovulation disorders.

Extensive research is being done to find better treatment outcomes of ovulation induction. Some of the recent studies are listed below:

  • Horowitz E, Levran D, Weissman A. Extension of the clomiphene citrate stair-step protocol to gonadotropin treatment in women with clomiphene resistant polycystic ovarian syndrome. Gynecol Endocrinol. 2017 Apr 28:1-4.
  • Haller L, Severac F, Rongieres C, et al. Intra-uterine insemination at either 24 or 48hours after ovulation induction: Pregnancy and birth rates. [French] Gynecol Obstet Fertil Senol. 2017 Apr;45(4):210-214.

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