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.

Reference

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

Birth control pills are one of the most popular and effective methods to prevent pregnancy when taken correctly. People will be surprised to know that birth control pills are also used in IVF to improve the chances of pregnancy.

How birth control pills affect the IVF cycle

Control The Cycle and Improve Response to Hormone Therapy

A typical IVF cycle begins with the administration of medications that stimulate and trigger the ovaries to release mature eggs. Once the mature eggs are collected, they are fertilized outside the body and become embryos. The embryos are then transferred into the uterus for implantation and pregnancy begins.

In many IVF protocols, there is a pre-stimulation step that occurs before the ovaries are stimulated with medications. The pre-stimulation step suppresses the women’s own natural hormones by using birth control pills. This is done for the following two reasons:

• Controlling the cycle. The doctors will be able to control the timing of the cycle through the use of birth control pills. This allows the clinic to avoid having too many patients with cycles that overlap, ensuring all patients receive the same quality of treatment and attention, and reduce scheduling conflicts.

• Improving the response to the hormone therapy. Birth control pills will help stimulate more eggs to mature at the same rate, resulting in more eggs being collected. It also decreases the chance of developing cysts (fluid‐filled sacs on the ovary), which is believed to reduce pregnancy losses and improve pregnancy outcome.

The continuing debate on using birth control pills in IVF

Possible Lower Rates of Live Births

The use of birth control pills in IVF cycle is not without controversy. There are debates on the efficacy of using birth control pills for pretreatment as contradictory data have been published on whether pretreatment with oral birth control pills have negative effects on IVF cycle outcome.

In 2015, there was a discussion between Juan A. Garcia-Velasco, Director of IVI-Madrid and Georg Griesinger, University Clinic of Schleswig-Holstein, Germany on the question “To pill or not to pill in GnRH antagonist cycles: that is the question!” The discussion concluded without a clear answer as there were not enough well designed and adequately powered studies to evaluate the efficacy of using oral birth control pill for pretreatment in IVF. 

In 2017, a systematic review looked at 30 clinical trials assessing pretreatment with oral birth control pills in more than 5,000 women undergoing assisted reproductive technology and concluded that oral birth control pills for pretreatment was associated with lower rates of live birth than no pretreatment. However, the overall quality of the evidence from the trials ranged from very low to moderate, which made the conclusion on the efficacy of oral birth control pills for pretreatment weak.

The debate on the efficacy of using oral birth control pills for pretreatment in IVF will continue until better studies are available. Until then, the use of birth control pills in IVF will be based on the clinical judgment and experience of the fertility doctor.

Reference

Farquhar C, Rombauts L, Kremer JAM, et al. Oral contraceptive pill, progestogen or oestrogen pretreatment for ovarian stimulation protocols for women undergoing assisted reproductive techniques. Cochrane Db Syst Rev. 2017; 5: CD006109. DOI: 10.1002/14651858.CD006109.pub3

Garcia-Velasco JA, Fatemi HM. To pill or not to pill in GnRH antagonist cycles: that is the question! Reprod Biomed Online. 2015; 30: 39–42.

Griesinger G, Venetis CA, Tarlatzis B, Kolibianakis EM. To pill or not to pill in GnRH-antagonist cycles: the answer is in the data already! Reprod Biomed Online. 2015; 31(1): 6-8.

Natural cycle IVF is IVF without the use of hormonal medications to stimulate the ovary to produce multiple mature eggs. Natural cycle IVF works with the woman’s own ovulation cycle to produce mature egg(s) and the fertility doctor collects the single dominate egg that is naturally matured by the body.

It is believed the risks associated with hormonal medications, the high costs, and multiple pregnancy can be avoided when using this method as compared to conventional IVF. There is also a modified natural cycle IVF, which uses hormonal medication to stimulate the ovaries but at low doses compared to conventional IVF.

How is it done?

The woman will go through a regular menstrual cycle and will be monitored with ultrasounds and blood tests to identify the maturation of the dominant egg. The dominate egg is then collected when it reaches the appropriate size of a mature egg.

Once the mature egg is retrieved, the procedures of fertilization and implantation are similar to conventional IVF. The collected mature egg is fertilized in the laboratory and it will grow into an embryo. When the embryo reaches the stage suitable for implantation, the fertility doctor will transfer the embryo into the uterus for implantation and pregnancy will hopefully begin.

Who should use it?

All women who have normal ovulation cycles can undergo natural cycle IVF but it is best used for certain groups. These include:

• Women who have poor response to stimulation medications
• Women who have high risk of developing ovarian hyperstimulation syndrome (OHSS) or want to avoid side effects associated with the medications used in conventional IVF
• Couple with male factor subfertility

What are the advantages of natural IVF?

• Less expensive. Natural cycle IVF eliminates the costs associated with hormonal medications, which account for a significant portion of the IVF cost.

• Less side effects. By using the body’s natural ovulation processes with minimal use of medications, natural cycle IVF reduces the risks of OHSS and other complications associated with hormone drugs.

• No multiple pregnancy. In natural cycle IVF, only one dominant egg is matured and collected for fertilization. This eliminates the chance of multiple pregnancy, which carry significant risks for both the mother and the child.

• More natural. Natural cycle IVF is the closest method to natural fertilization. It offers fewer medications, fewer side effects, fewer office visits, and the IVF cycle is less time consuming, which makes it is less physical and mentally stressful for the patients.

What are the drawbacks of natural IVF?

Although there are many advantages to using natural cycle IVF if the patient is a good candidate, there are some disadvantages to take into consideration. 

• Cycle cancellation. Not using hormone medications to stimulate the ovaries limits the control the fertility doctor has over the IVF cycle. This allows for many unexpected events to occur that can lead to the cancellation of the cycle. These include a premature LH surge, no ovulation, no fertilization, or embryo arrest. Natural cycle IVF can become a time-consuming and more stressful process if the cycle is cancelled and the patient needs to repeat the IVF cycle.

• No extra eggs/embryos. In a natural cycle IVF, there is only one dominant egg that is ovulated. This means there are no extra eggs or embryos to use in an event the retrieved mature egg is found to be not viable or if the patient wants to have additional children later in the future.

How does the success rate of natural cycle IVF compare to conventional IVF?

Many people claim that since the matured egg is naturally selected in natural cycle IVF, the matured egg is of higher quality than those in conventional IVF. They also believe drugs used to stimulate the ovaries may have a negative effect on the eggs collected. Studies show that there is no difference in the fertilization rates, embryo quality and implantation rates between natural IVF and conventional IVF.

In fact, a conventional IVF cycle offers a better chance to have a baby as it has extra eggs or embryos frozen in the event the first cycle does not work. Where as in natural cycle IVF, the patient will have to repeat the whole IVF cycle to obtain an egg for fertilization. Natural cycle IVF can be a good option for some women who want to limit the use of hormone medication but it is not the best choice for everyone. 

Reference

Allersma T, Farquhar C, Cantineau AEP. 
Natural cycle in vitro fertilisation (IVF) for subfertile couples.
 Cochrane DB Syst Rev. 2013;8. DOI:10.1002/14651858.cd010550.pub2.

Celia, G.F, Botes, A, Gordon, J.D, DiMattina, M. Natural cycle IVF produces similar implantation rates compared with stimulated IVF. Fertil Steril. 2010; 94(4): S162.

In vitro maturation (IVM) is a new technique in assisted reproductive technology in which immature eggs are collected from the ovaries and matured in the laboratory before being fertilized.

IVM of human eggs was first introduced in 1965 but the first successful pregnancy from IVM was not reported until 1991. Since then, IVM has advanced significantly to become an infertility treatment options in recent years.

How Does IVM Work?

First, the patients undergo blood tests and ultrasound at the start of the IVF cycle to determine the best time for collecting the immature eggs. Only a minimal hormone stimulation of the ovaries (or no stimulation in some cases) is required depending on which regimen is used by the fertility doctor.

When the best time to collect the immature eggs is determined, usually when the egg diameter is between 6 mm and 12 mm, the immature eggs are collected transvaginally using a small ultrasound guided needle. Patients are provided local anesthesia or general anesthesia to reduce discomfort during this process.

The collected immature eggs are matured in the laboratory under specific environment for 24 to 48 hours. Once the maturation is complete, the matured eggs are fertilized with sperm using intracytoplasmic sperm injection (ICSI) and incubated to become embryos or the mature eggs can be frozen and preserved for future use.

After the embryos grow to a certain stage and ready for transfer, the embryo(s) are transfer into the uterus for implantation and pregnancy is confirmed through blood tests.

What are the advantages of IVM?

• Less side effects. IVM eliminates complications from stimulation drugs, especially OHSS.

• Less cost. IVM reduces the need for hormone stimulation drugs and frequent sonographic monitoring compared to conventional IVF.

• Less time. IVM requires no need to prepare patients before starting fertility treatment and the procedure can be performed urgently, irrespective of the phase of the menstrual cycle without affecting the quantity and maturation rate of the eggs. 

What are the disadvantages?

Not Enough Data to Confirm Its Efficiency and Safety

Although IVM appears to be a promising technique, it is a relatively new procedure and there is still no strong evidence from randomized clinical trials to confirm its efficiency compared to IVF. A few observational studies in groups of women with PCOS found a high maturation rate of eggs up to 80.3% and clinical pregnancy rates from 21.5% to 50% per cycle.

One of the debates with IVM is the long-term safety of the child’s development and health. As less than 3000 children have been born through IVM, there is limited data regarding the developmental and health outcomes of the children. Currently, studies from a number of fertility centers have shown no differences concerning the risk of congenital defects in children after IVM compared with conventional IVF.

Who would benefit from IVM?

IVM was first proposed to be used in women who are at risk for ovarian hyperstimulation syndrome (OHSS) but now the indications for IVM have expanded. There are a few broad groups of patients who may benefit from IVM:

• Women with polycystic ovarian syndrome (PCOS) who are at high risk for OHSS.

• Fertility preservation in cancer patients who cannot undergo ovarian stimulation (i.e. patients with hormonally sensitive cancers) and/or cannot delay their cancer treatment.

• Situations where no suitable standard fertility treatment exists; such as oocyte donation, FSH resistance, and other contraindications for ovarian stimulatory drugs.

IVM technology has continued to improve since the first IVM-induced pregnancy in 1989 and has shown great promise to making IVF safer and easier on the women. However, as a relatively new procedure, there are many unknowns in regards to the long-term health of the child born through IVM or its efficacy compared to other established fertility treatments. One should fully understand the risk and benfits of IVM before considering this option.

Reference

Cha KY, Koo JJ, Ko JJ, Choi DH, Han SY, Yoon TK. Pregnancy after in vitro fertilization of human follicular oocytes collected from nonstimulated cycles, their culture in vitro and their transfer in a oocyte program. Fertil Steril. 1991; 55: 109-13.

Chang EM, Song HS, Lee DR, Lee WS, Yoon TK. In vitro maturation of human oocytes: Its role in infertility treatment and new possibilities. Clin Exp Reprod Med. 2014; 41(2): 41-6.

Berwanger AL, Finet A, El Hachem H, Le Parco S, Hesters L, Grynberg M. New trends in female fertility preservation: in vitro maturation of oocytes. Future Oncol. 2012; 8: 1567–73.

Maman E, Meirow D, Brengauz M, Raanani H, Dor J, Hourvitz A. Luteal phase oocyte retrieval and in vitro maturation is an optional procedure for urgent fertility preservation. Fertil Steril. 2011; 95: 64-67.

Siristatidis CS1, Vrachnis N, Creatsa M, Maheshwari A, Bhattacharya S. In vitro maturation in subfertile women with polycystic ovarian syndrome undergoing assisted reproduction. Cochrane Database Syst Rev. 2013; (10): CD006606. DOI: 10.1002/14651858.CD006606.pub3.