Infertility Treatment Options

Infertility Treatment Options

Infertility treatment depends on multiple factors such as age, duration of infertility, cause of infertility, and financial burden. Some patients may need only one or two treatment options, while others may need a combination of different treatment options.

Lifestyle therapies


  • Weight optimization: Women who are either overweight or underweight have greater risk for ovulatory dysfunction and reduced fertility. Weight loss and exercise is recommended as the first-line management for obese women, especially women with polycystic ovarian syndrome (PCOS). Even a 5% to 10% reduction in body weight has been shown to restore ovulation in women with PCOS. On the opposite spectrum, women with low body weight and ovulatory dysfunction are advised to gain weight, modify their diet, and reduce exercise.
  • Stress management: Stress has been associated with pregnancy failure. Patients with higher stress levels have lower pregnancy rates when undergoing IVF treatments. Some commonly used stress management strategies include meditation, breathing exercises, therapy, and joining support groups.



Women with ovarian problems are commonly prescribed ovulation induction agents that help stimulate the ovaries. Below are some commonly prescribed medications.

  • Clomiphene citrate. This oral drug is often the initial treatment for many infertile women who have irregular menstrual cycles. Clomiphene works by indirectly increasing the reproductive hormones (LH and FSH) levels, which in turn, stimulate more eggs to develop.
  • Letrozole. This oral drugs works by decreasing estrogen levels and was originally developed for breast cancer treatment. Letrozole is commonly used in women with PCOS. Recent studies show letrozole may work better than clomiphene in women with PCOS to induce ovulation and become pregnant.
  • Metformin. This oral drug is a common diabetic drug used to control high blood sugar levels. Metformin is commonly prescribed to women with PCOS. Women with PCOS have higher insulin resistance and this negatively affects ovulation. Metformin can help reduce the insulin resistance and thereby increase the likelihood of ovulation.
  • Gonadotropins. Although clomiphene citrate is easy to use and its use leads to ovulation in most patients, the pregnancy success rates are low. Patients who cannot get pregnant using clomiphene citrate are often classified as “clomiphene citrate resistant.” The next step in these patients can be the administration of gonadotropins (reproductive hormones) injections. These medications stimulate the ovaries directly to produce more eggs. Gonadotropin medications include FSH and human chorionic gonadotropin (hCG), which contains both LH and FSH. Gonadotropin injections carry the risks of excessive ovarian response, need close medical monitoring, and are typically expensive to purchase.


Corrective surgery can be an option for some anatomic abnormalities of the female reproductive tract that is causing infertility.

  • Fallopian tubes abnormalities. If the fallopian tubes are blocked or if there are adhesions, laparoscopic surgery may be performed to re-open the tube or create a new tubal opening to allow the sperm and the fertilized egg to travel through the fallopian tube unobstructed.
  • Uterine abnormalities. Doctors may suggest laparoscopic or hysteroscopic surgery to correct uterine abnormalities. Some examples are removing fibroids in patients with leiomyomas, restoring the normal uterine cavity size in patients with intrauterine adhesions, and restoring the pelvic anatomy in patients with pelvic adhesions.
Assisted reproductive technology (ART)

Assisted reproductive technology is used to achieve pregnancy in infertile couples for whom the underlying cause of infertility cannot be effectively treated or is unknown.

  • Intrauterine insemination (IUI). IUI is typically the first step in the treatment of young couples with no evidence of tubal damage or severe male factor infertility. This procedure involves injecting previously collected sperm into the uterus by a catheter placed inside the uterine cavity through the vagina.
  • Intracytoplasmic Sperm Injection (ICSI): ICSI is used to assist the fertilization process when a male’s sperm is abnormal. This technique involves using specialized equipment to select and pick up one sperm that is then directly injected into the inner part of the egg held with a specialized pipette. 
  • In vitro fertilization (IVF): IVF is a medical and surgical procedure that involves fertilizing the egg outside the woman’s body and transferring the resulting embryo back into the woman’s body. The procedure is a multistep process over 4 to 6 weeks that requires medications to stimulate egg production in the ovaries, minor surgical procedures to retrieve the eggs and implant the embryo, and clinical monitoring by the doctor throughout the process.




Crosignani PG, Colombo M, Vegetti W, et al. Overweight and obese anovulatory patients with polycystic ovaries: parallel improvements in anthropometric indices, ovarian physiology and Fertility rate induced by diet. Hum Reprod. 2003;18(9):1928-32.

Thiering P, Beaurepaire J, Jones M, et al. Mood state as a predictor of treatment outcome after in vitro fertilization/embryo transfer technology (IVF/ET). J Psychosom Res. 1993;37(481):481-91.

Legro RS, Brzyski RG, Diamond MP, et al. Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. N Engl J Med. 2014;371:119.



Infertility 101

Infertility 101

How common is it?

Infertility in women is ranked the 5th highest serious global disability. About 6% of married women aged 15 to 44 years in the United States are unable to get pregnant after one year of trying. Infertility is defined as not being able to get pregnant after one year or longer of unprotected sex. It can be further divided into:

  • Primary infertility: Infertility without any previous pregnancy.
  • Secondary infertility: Fertility occurring after having a child in the past.


Time required for conception, approximately 50% of women will be pregnant at 3 months, 75% at 6 months, and more than 85% by 1 year. (Adapted from Barbara LH. ed., (2016). Evaluation of the Infertile Couple. In: Williams gynecology, 3rd ed , pp. 427- 446.)

How is it diagnosed?

Fertility is not just a woman’s problem; both men and women contribute to infertility. In about 35% of couples with infertility, both male and female fertility problems were identified. In about 8% of cases, only the male problem was identified as contributing to the infertility. An infertility evaluation is recommended after 1 year of unprotected sex for women under 35 years or after 6 months for women 35 years and older.


Female Infertility Evaluation:

The evaluations for female infertility fall into two basic categories: ovulatory function and health of the reproductive organs


Ovulatory function:
  • Ovulation function is typically evaluated with blood tests to determine if ovulation occurs. A progesterone level >3ng/mL a week prior to expected menses would indicate recent ovulation.  Patients can also use over-the-counter ovulation predictor kits to measure urinary luteinizing hormone (LH) concentrations to determine ovulation. As these kits are not 100% accurate, a blood test may be needed to confirm the results. If ovulation is not detected, a further evaluation would be conducted to determine the cause for the lack of ovulation.
  • Some women have regular menses but have a reduced response to ovarian stimulation. These patients will need to have their ovarian reserve evaluated. Various ovarian reserve tests are available to provide an indirect assessment of the woman’s ovarian reserve. Day 3 FSH levels and estradiol (E2) levels are commonly used to determine the ovarian reserve. Other tests include clomiphene citrate challenge test (CCCT), anti-mullerian hormone (AMH) level, and antral follicle count (AFC) using transvaginal ultrasound.


Evaluation of the reproductive organs:

The causes of female infertility from anatomic abnormalities are usually in the following areas: ovaries, fallopian tubes, and uterus. Any problems in these organs can cause infertility or difficulty in achieving pregnancy. Examples include obstruction in the fallopian tubes, polyps in the uterus, intrauterine adhesions, endometriosis, and ovarian cysts.

There are several procedures that are used to evaluate the reproductive organs: hysterosalpingogram (HSG), transvaginal sonography (sonohysterography), hysterosalpingo-contrast sonography (HyCoSy), hysteroscopy, and laparoscopy.

Initial evaluations generally involve procedures that are less invasive like HSG, sonohysterography, and HyCoSy. If abnormalities were found during the initial evaluation, more invasive procedures like hysteroscopy, laparoscopy, and MRI would be required for further evaluation.

  • Hysterosalpingogram (HSG) is a radiographic tool that evaluates the uterine cavity and the fallopian tubes. This procedure is commonly used to look for abnormalities of the uterus and to look for obstructions or blockages in the fallopian tube. If abnormalities are found during the HSG, further evaluations with more invasive procedures will be required. HSG involves a contrast media that is infused through a catheter from the vagina into the uterus and a fluoroscopy camera. This procedure is minimally invasive and is associated with minimal complications. However, there may be slight discomfort when the catheter is injected and vaginal spotting may occur for a few days after the procedure.


Examples of hysterosalpingogram findings. A. Normal hysterosalpingogram. B. Bilateral hydrosalpinges, distally blocked fallopian tubes filled with serous or clear fluid. (Adapted from Barbara LH. ed., (2016). Evaluation of the Infertile Couple. In: Williams gynecology, 3rd ed , pp. 427- 446.)

  • Transvaginal sonography (VS) or sonohysterography uses ultrasound to provide images and assess the reproductive organs. This procedure uses a transducer that is placed in the vagina and a monitor to view the images. The images produced are typically 2D but 3D/4D ultrasound images are also available. Saline can be infused into the uterus to increase the sensitivity and specificity for detecting defects in the lining of the uterus like intrauterine adhesions and polyps and is the preferred procedure for assessing the uterine cavity. When saline is used with sonography, the procedure is called saline infusion sonohysterography. These procedures are simple and well tolerated, although some patients may have some cramping during the procedure.
  • Hysterosalpingo-contrast sonography (HyCoSy) is a type of sonohysterography that uses ultrasound and contrast media injected into the uterus through the vagina to provide images of the uterine cavity, fallopian tubes, and the ovaries. This procedure is simple and well tolerated with minimal side effects. Like the saline infused sonohysterography, some patients may have some cramping during the procedure. HyCoSy is commonly used to quickly look for tubal obstructions and assess the uterine cavity.
  • Hysteroscopy is an endoscopic evaluation used to examine the uterine environment and is the definitive method for evaluating the uterine cavity. This procedure involves a thin, lighted telescope-like device called a hysteroscope that is inserted and gently moved through the cervix and into the uterus. Hysteroscopy is typically not done during in an initial evaluation and has limitation in evaluating the fallopian tubes and the adjoining structures to the uterus. This is an invasive procedure and may involve anesthesia. Hysteroscopy is a relatively safe procedure but complications such as bleeding, infection, and injury to the reproductive structure can occur.
  • Laparoscopy is a direct inspection of the pelvic anatomy using a special instrument called the laparoscope. The laparoscope is a long, slender device with a camera that is inserted into the abdomen through a small incision and the abdominal and pelvic organs are then viewed on an electronic screen. Laparoscopy can be used in patients suspected to have endometriosis or pelvic adhesions. This procedure is not performed during an initial fertility evaluation, as it is invasive and expensive. Some complications that can occur with laparoscopy include bleeding, infection, and damage to the pelvic organs.



Male Evaluation:

The evaluation for potential male infertility concerns mainly with the sperm. As such, the initial evaluation typically consists of collection of semen and basic health assessment. The results of the semen analysis will further guide the evaluation process.


Initial diagnostic tests:
  • Semen analysis is the first test done to evaluate male infertility. For this test, the male is asked to refrain from ejaculation for 2 to 3 days before submitting the sample. A semen analysis evaluates the number of sperm, the sperm’s movement, and the shape of the sperm. If the initial semen analysis finds abnormal results, an additional semen sample is requested and analyzed to confirm the initial results. An abnormal result could indicate many different causes including infertility, infection, hormonal imbalance, and genetic defects.
  • Hormonal testing is often done in males to detect any hormone abnormalities that may affect sperm production. This is a blood test that typically measures FSH, LH, testosterone, prolactin, and TSH levels.
  • The results from the physical examination, semen analysis, hormonal testing, and patient’s medical history will typically be enough to determine the cause of male infertile in most cases. If the cause is still not defined, further evaluation will be done.
Second-level diagnostic tests:
  • Genetic assessment. Males with severely decreased sperm counts have a high risk of having genetic abnormalities. Although the low sperm count cannot be corrected, the genetic test will provide information about the status of male health and possible genetic abnormalities their offspring may inherit.
  • Bacteriological examination and transrectal/scrotal ultrasound. These tests can identify anatomical abnormalities resulting from chronic inflammation, which usually cause obstruction of the ductal outflow tract. Testicular ultrasonography can be used as a diagnostic tool and is especially useful in patients with an increased risk of cancer.
Third-level diagnostic tests:
  • Testicular biopsy. This invasive procedure is done to differentiate testicular failure, whether it is primarily from obstruction or from other causes. Today, testicular biopsy can be considered as both a diagnostic and treatment procedure. Sperm can be obtained from testicular biopsies of males whose semen contains no sperm. The collected sperm would then be used to fertilize an egg in the lab to create an embryo to be implanted into the uterus.



Infertility definitions and terminology. (Assessed 2017–05–12)

Infertility FAQs. (Assessed 2017–05–12)

Grimbizis GF, Solakidis D, Mikos T, et al. A prospective comparison of transvaginal ultrasound, saline infusion sonohysterography, and diagnostic hysteroscopy in the evaluation of endometrial pathology. Fertil Steril. 2010;94(7):2720.

De Hondt A, Peeraer K, Meuleman C, et al. Endometriosis and subfertility treatment: a review. Minerva Ginecol. 2005;57:257.

Common IVF Blood Test

Common IVF Blood Test

Whether you are actively trying to concieve and unable to get pregnant after 12 months or you are planning for an egg freeze cycle and would like to assess your ovarian reserve, blood tests are a standard part of the fertility work up done by the fertility doctor to assess hormonal causes of infertility. Below are common blood tests ordered by the fertility doctor.


The Hormones

Follicle-stimulating hormone (FSH) – a reproductive hormone that controls the development of the eggs and the menstrual cycle in women and sperm in men. In men, FSH levels are used to help determine the cause for low sperm count. High FSH levels may suggest testicular dysfunction and low FSH levels may suggest dysfunction of the pituitary gland. In women, a Day 3 FSH test can be used to assess the woman’s ovarian reserve (the quality and the quantity of eggs). A Day 3 FSH value less than 10 mIU/mL is suggestive of adequate ovarian reserve. A high FSH level of 10 mIU/mL to 20 mIU/mL is associated with infertility.

Anti-mullerian hormone (AMH) – a hormone secreted by the cells in the ovary to support the eggs and is used to determine the size of the egg pool. AMH levels are correlated with the number of eggs retrieved after stimulation and is the best biomarker for predicting poor or excessive ovarian response. AMH can be measured anytime during the menstrual cycle.

  • AMH <0.5 ng/mL predicts reduced ovarian reserve with less than three follicles in an IVF cycle
  • AMH <1.0 ng/mL predicts baseline ovarian reserve with a likelihood of limited eggs at retrieval
  • AMH >1.0 ng/mL but <3.5 ng/mL suggests a good response to stimulation
  • AMH >3.5 ng/mL predicts an excessive response to ovarian stimulation and caution should be exercised in order to avoid ovarian hyperstimulation syndrome (OHSS)

Estradiol (E2) – a derivative of estrogen and the main sex hormone in women. Estradiol helps to maintain a healthy pregnancy. A Day 3 estradiol level with FSH can be used to assess the ovarian reserve. A high estradiol level (greater than 60 to 80 pg/mL) in conjunction with a normal FSH level has been associated with lower pregnancy rates.

Progesterone – a hormone that has multiple functions in the body including preparing a woman’s body for pregnancy and maintaining the pregnancy. Progesterone levels are commonly used to assess ovulation in women and to monitor the success of induced ovulation. A progesterone level greater than 3 ng/mL is evidence of recent ovulation. Progesterone levels are typically obtained on Day 21 in a regular 28-day cycle. If the woman has irregular cycles, the test is typically started 7 days before the presumed onset of menses and repeated weekly thereafter until the next menstrual cycle starts.

Luteinizing Hormone (LH) – a reproductive hormone that stimulates the releasing of the egg from the ovary in women and stimulates the production of testosterone in men. In both men and women, LH is often used in conjunction with other tests (i.e. FSH, testosterone, estradiol, and progesterone). In women, LH levels can be used to evaluate the function of the ovaries and determine a LH surge (ovulation).

Prolactin – a hormone commonly known to help women produce milk after birth and plays an important role in reproduction. Prolactin levels are used along with other hormone tests to help diagnose the cause of infertility and erectile dysfunction in men and the cause of menstrual irregularities and/or infertility in women.

Testosterone – the main sex hormone in men. This test may be done when male infertility is suspected or when a man has a decreased sex drive or erectile dysfunction.




Lindsay TJ, Vitrikas KR. Evaluation and treatment of infertility. Am Fam Physician. 2015;91(5):308-14.


When is the optimal time to freeze your eggs?

When is the optimal time to freeze your eggs?

Women who delay childbirth may face infertility by the time they are ready to get pregnant as a women’s fertility is strongly influenced by her age. Age-related decline in fertility is primarily from the decline in the quality and quantity of the eggs. As such, a reasonable strategy to preserve fertility in women who wish to delay childbirth is to freeze their eggs.

Egg freezing is an increasingly popular method to preserve fertility but one must carefully consider if it is the right time to undergo this procedure. If it is done too early in life, the preserved eggs may never be used or if done too late, it could be an ineffective procedure.

What are the factors affecting success rates using egg freezing?

Age +Number of Eggs Retrieved

The two most critical factors determining the probability of achieving a child using previously frozen eggs are the woman’s age at the time of egg collection and the total number of egg collected.

The number of eggs naturally decline as the women ages from approximately 200,000 eggs at the onset of puberty to around 1,000 eggs remaining at menopause. After the age of 37, the rate of decline accelerates rapidly.

As the number of eggs progressively decrease, the quality of the eggs also decline and eventually a minimum threshold is reached where pregnancy is no longer possible. It is estimated that after the age of 45, most of the eggs will have abnormal number of chromosomes.

What are the factors to consider for egg freezing?

Age + Estimated Time for Possible Use + Budget

When a woman decides to freeze her eggs, there are several factors she needs to consider. These include 1. the woman’s age at the time of egg freezing, 2. the intended wait time before pursuing pregnancy and 3. the cost-effectiveness of egg freezing.

Several studies found that reproductive aging is primarily related to the age of the egg and is not influenced very much by the age of the uterus. This means that the probability of pregnancy when using previously frozen eggs is determined primarily by the age of the woman when the eggs were collected rather than the age when she gets pregnant.

If egg freezing is undertaken too early, there is an increased chance that the woman will never be required to use the stored eggs to have children. The woman would have also been unnecessarily exposed to the financial burden and risks associated with ovary stimulation and egg collection.

If egg freezing is undertaken at an older age, the chances of pregnancy will be low due to the reduced number of collected eggs and the decreased quality of the eggs.

In a study by Mensen et al., his team found the highest probability of live birth when egg freezing was performed at the ages <34, and little benefit over no action was seen at the ages 25-30 years. If the only consideration is maximizing live birth rates at any cost, egg freezing should be performed before the age of 34 years. However, when attempts to conceive are delayed for a long period of time and cost-effectiveness is considered, egg freezing can be considered at the age of 37 years.

What is the maximum age for egg freezing?

The maximum age for attempting egg freezing may be as high as 45 years, but the success was limited to those patients producing >5 eggs in response to ovarian stimulation according to a study by Spandorfer et al. in 2007. In this study, patients older than 46 could also get pregnant, but none of these pregnancies resulted in a live birth child.

In some countries, there is the age-limit for IVF using donor eggs. In the Netherlands, the age is 45 years and in Belgium, the ages is 47 years. 

Many questions for egg freezing may come from women aged 38-44. Would they benefit from egg freezing? Egg freezing from women at this age group will result in fewer live birth rates and would need to undergo multiple IVF cycles to potentially achieve pregnancy. Women in this age group need to be thoroughly counseled about the low probability of success and the time and resources required to undergo multiple cycles.




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Egg freezing vs. Embryo freezing

Egg freezing vs. Embryo freezing


In the past, women only had the option of freezing an embryo if they wanted to preserve their fertility. This meant that if the woman was single and wanted to preserve her fertility, she had to find a sperm donor to fertilize the egg before it was frozen.

However, after the ASRM (American Society for Reproductive Medicine) lifted the experimental label for oocyte cryopreservation (egg freezing) in 2012, women today can either freeze their eggs or embroyos for fertility preservation. So which is a better option for you?

Understanding the  Fertility Preservation Process

The beginning process of egg freezing and embryo freezing is the same. First, the woman receives hormone medications to stimulate the ovaries to produce multiple mature eggs. The fertility doctor will monitor the maturation of the eggs during this time to determine the timing of the retrieval. Once the eggs are matured, the patient will undergo a minor surgical procedure to retrieve the matured eggs.

After the retrieval of the matured eggs, the process for egg freezing and embryo freezing diverges. In egg freezing, the collected eggs are processed and frozen soon after the retrieval. In embryo freezing, an additional step of fertilizing the egg with sperm is needed before it is frozen. The collected eggs are processed, fertilized with sperm, developed into an embryo before freezing.

The embryos and eggs are typically frozen by a process called vitrification. The frozen eggs or embryos will be stored at deep sub-zero temperatures (-196 degrees Celcius) in liquid nitrogen until they are ready to be thawed for future fertility procedures.


The Differences: Frozen Embryos vs Frozen Eggs 

Embryo freezing

For just freezing embroyos

Frozen embroyos are more stable and less prone to damage during the freezing and thawing processes compared to frozen eggs.  Also, for retrieved embryos you can test for chromosomal abnormalities, which can increase the odds for live births, but you cannot test retrieved eggs. Therfore, using frozen embryos can potentially provide a better pregnancy outcome later in life than using frozen eggs.

For IVF cycling

There are also many other benefits of freezing embryos. In a standard IVF cycling, freezing embryos can minimize the risk of multiple pregnancy by reducing the number of embryos transferred during a fresh cycle, avoid repeating stimulation cycles, and increasing cumulative pregnancy rates. Some studies showed that women who had transfers of fresh and frozen embryos obtained an 8% additional births by using their frozen embryos. Additionally, with the success rates of post thaw embryo transfer nearing those of fresh embryo transfer couple, the use of frozen embryos is now a routine procedure in assisted reproduction technology. Thus, the number of live births in woman undergoing IVF with post thaw embryo doubled from 12% in 1997 to 25% in 2011. 

Egg freezing

Diversity: More patient populations

Egg freezing can offer more options for diverse patients populations in fertility preservation compared to embryo freezing. These include single women who will undergo fertility compromising cancer treatments, women looking to postpone childbirth to pursue educational or career goals, and those who have diminished ovarian reserve and haven’t met their significant other.

Improved technology: Comparable to retrieved fresh eggs

The technology for egg freezing has improved with vitrification and studies have shown signficant improvements in the post thaw survival rates and clinical pregnancy rates compared to the traditional slow freezing method. Freezing with vitrification has been shown in several studies to have high post thaw survival ranging from 79% to 99%. In 2011, Cobo and Diaz conducted a systematic review comparing vitrified and fresh eggs that showed similar fertilization rates and clinical pregnancy rates between the two groups.

Controversies of Embryo and Egg Freezing

The storage of frozen embryos has generated ethical, legal, and religious concerns in some countries due to the concerns on the fate of the surplus frozen embroyos in storagge. Due to this controversy, countries like Italy and the United Arab Emirates have enacted specific laws that prohibit embryo freezing.

Egg freezing is controversial in some countries with conservative family values, therefore its use is strictly controlled. In China, egg freezing is prohibited to single women whereas in Singapore, only women with certain medical needs such as fertility preservation for cancer patients undergoing chemotherapy are allowed.


Safety of egg and embryo freezing

Recent data shows no increase in the number of congenital abnormalities observed in thawed eggs or embryos. Although freezing eggs and embryos are now well-established procedures, caution is advised until there are sufficient data to rule out potential long-term side effects for these children.


Which is better?

Egg and embryo freezing are now an established technology with high success rates and used for a wide range of indications. It just comes down to lifestyle and circumstances. Women who do not have partner or do not wish to store embryos due to ethical and morals considerations are good candidates for egg freezing. While for couples who want to achieve children later, embryos freezing could be a better option than freezing eggs or sperm separately. 



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