Insider’s Guide to: “What to Expect” When Experiencing Infertility

By: Elie Salomon

This guide was written by a woman who experienced “unexplained infertility” and conceived through various types of Assisted Reproductive Technologies (A.R.T.)

I am not a physician, but rather a woman sharing my experience in the hopes of making the path simpler for those who come after me. I went through I.U.I. (Intrauterine Insemination), Fresh Cycle IVF, Frozen Cycle IVF, and IVF with PGD (Pre-implantation Genetic Diagnosis). This guide has been reviewed by Dr. David Reichman, MD, Reproductive Endocrinologist at Cornell Weill CRM.

Although it is not meant to be exhaustive, this guide contains a LOT of information- more than you might want to know at this point. Feel free to skim and read the parts that interest you, and try not to get overwhelmed.  Not everything here will be relevant to every couple.  Keep in mind that every couple’s experience in the fertility world is going to be different. Some couples will quickly receive a diagnosis and a straightforward treatment plan; other couples have a road that will be much more winding and complex- and everything in between.  Some couples see success relatively quickly with treatments, others need to go through treatments for a long time- and everything in between.  Whatever your experience, I hope this guide will be helpful, and remember that Yesh Tikva is always there for you.   

PART I:  WHAT TO EXPECT ON YOUR FIRST CONSULTATION WITH A REPRODUCTIVE ENDOCRINOLOGIST:

First of all, this is a brave step you are taking in looking for medical help. Hashem provided the medical community with this knowledge in order to help create babies where years ago it was unknown. A good support system always helps throughout this process, be it family, friends, or a support group.

When you call for your first appointment, expect that you will likely get an appointment with a specialist after 10 am. This is because routinely, fertility offices have morning monitoring from 7am – 9am to do daily monitoring of already established patients. (More on that later.) Some offices only perform morning monitoring on certain days of the week, so the other days are more flexible.

You and your partner will be present. They will take a history of all potential conditions relating to your cycle and other aspects of fertility. Come prepared with some information! For the gynecological intake survey they may need/want to know:

  • First day of last menstrual cycle
  • Age of your first period
  • In the last three months you ovulated on day X,Y,Z
  • In the last three months you had a cycle length of A,B,C.
  • You bleed for __ # of  days

In addition to you, they will take a history of your partner as well. If possible, you should both try  and ask your parents and any married siblings if there is any history of reproductive issues, genetic abnormalities, and miscarriage (obviously this kind of conversation is not going to be realistic in all families). NONE OF THESE THINGS SHOULD SCARE YOU. Knowledge is POWER and the more you know, the more likely it is to help get a diagnosis.

After taking an oral history, you will have your blood drawn, A LOT OF BLOOD. In taking your blood they will test for basic health issues that you may not realize are important to fertility.

ABBREVIATIONS YOU WILL COMMONLY SEE BEING REQUESTED WHEN THEY TAKE THE FEMALE’S BLOOD THROUGHOUT HER CYCLE ARE:

  • LH – Luteinizing Hormone is created by the pituitary gland to help a woman’s cycle, mainly in ovulation. It increases just before ovulation and is known as an LH surge. If you have ever bought an ovulation kit, once you see the LH surge, it is likely you will ovulate in 24-48 hours and it is the optimal time to get pregnant.
  • FSH – Follicle Stimulating Hormone, also released  from the pituitary gland, stimulates the ovaries to produce eggs. The test is used to monitor:
  • E2 – Estradiol is a hormone released from the ovaries and adrenal glands. This test is conducted to see how well your ovaries work, and this number will rise and fall depending on at what point you are in your cycle.
  • P4 – Progesterone helps make a woman’s uterus ready for a fertilized egg to be implanted. This test is used to:
    • Determine if a woman is ovulating
    • Evaluate a women with repeated miscarriages (though there is a “Repeat Pregnancy Loss Panel” for that as well)
    • Determine the risk of miscarriage or ectopic pregnancy early in pregnancy
  • BetaHCG – Beta Human Chorionic Gonadotropin: this is a blood pregnancy test. It measures the presence of HCG hormone in your blood. If it is positive, the numbers should approximately double every two days when early in the pregnancy, if rising <53% in 48 hours, you will likely have a miscarriage or ectopic pregnancy.

 

In addition to taking blood, they may actually do a TRANS VAGINAL ULTRASOUND on this visit. They will insert a long wand into your vagina in order to see the thickness of your uterine lining (endometrium) and check your ovaries to see if there are any cysts or follicles growing. Some patients find these ultrasounds uncomfortable, but they will occur extremely frequently, and you will get used to them!

The doctor’s first goal is to find a diagnosis.  Possible diagnoses include the following (or any combination thereof:)

  • male factor
  • female factor- ovulatory dysfunction
  • female factor- ovarian reserve
  • female factor- uterine/implantation issue
  • genetic/chromosomal issue in one or both parties (associated with recurrent miscarriage)

PART 2: THE NEXT STEPS- FURTHER TESTING

Depending on the initial medical histories of the man and woman, the doctor will decide on the next steps to be taken in finding a diagnosis. There is no set diagnostic plan, rather it is customized to each couple. Sometimes further testing may be required of the male, and sometimes the female. It may or may not be necessary for the woman to endure a full workup. It is best to ask your doctor the thought process behind your specific diagnostic pathway, so feel free to ask so you can understand fully what is going on.

(Note:  At times, if a couple has a rabbi they are consulting, it could happen that the rabbi desires more female testing than what the doctor recommends  before he (the rabbi) will permit a semen analysis.   If you find yourself in this situation, it is always good to open doors of communication between your doctor and rabbi. Allow them to speak directly and agree upon a plan.   Some aspects of female testing can be  financially taxing if not covered by insurance

[as well as uncomfortable, emotionally taxing, and time-consuming] so don’t be afraid to enable this conversation.)

Here are some of the hoops you and your spouse may have to jump through in  order to further understand your situation in order to come up with a personalized fertility plan:

FOR THE FEMALE:

They will possibly schedule a Hysterosalpingogram, also known as an HSG. This is a procedure performed either  by a radiologist  or a reproductive endocrinologists who will inject a dye into your uterus and the dye should flow into your fallopian tubes. If the dye does NOT flow easily, there is a chance of blockage, hindering your chance to conceive naturally. DON’T FRET; this can be overcome by A.R.T.  Moreover, if only one tube shows spillage on the HSG, it is actually quite likely that both tubes are open, unless there is an obvious abnormality in the tube without spillage.   They will take images with an X-RAY to be analyzed by the radiologist and your physician. This is can be an EXTREMELY PAINFUL procedure for some women. If they do not advise you to take 600mg of MOTRIN, ask if you can 45 minutes ahead of the procedure.  (My doctor mentioned that in his experience about 65% of women have 6 out of 10 pain for 60 seconds, 34% feel very little, and 1% are screaming and the test is stopped.)

{DO NOT WORRY, IF YOUR TUBES HAVE A BLOCKAGE, IT CAN BE OVERCOME BY USING I.V.F. , which will be explained later.}

FOR THE MALE:

During the first appointment the male will also be required to give blood. They will also discuss the need for a semen analysis (S.A.) The purpose of this procedure is to check for the following:

  1. Concentration: number of sperm found per milliliter (ml) of semen
  2. Motility: ability of the sperm to swim. Healthy sperm move forward, straight and fast.
  3. Morphology: the size and shape of the sperm. Some may be healthy and robust, while others may have abnormal heads, tails, or mid-pieces.

{DO NOT WORRY, IF ANY OF THESE POINTS, OR ALL, ARE AN ISSUE, IT CAN LIKELY BE RESOLVED WITH TREATMENTS SUCH AS:

  1. Intrauterine Insemination (IUI) for mild male factor (more on IUI below).
  2. In Vitro Fertilization (IVF) for moderate-severe male factor. This treatment is often done with Introcystoplasmic Sperm Injection (ICSI)in which a single sperm is manually injected into a single egg (more on IVF & ICSI below).
  3. Aspirating the testes for sperm (if no sperm appear in a standard semen analysis, there is a significant chance that sperm may be located “stuck” inside the testes and can be removed surgically.)

Sometimes, before attempting these treatments, the man may be treated with clomid or other drugs or possibly undergo surgery (such as a varicocele repair).   If these measures are not successful the couple will be advised to proceed with the above possible treatments. }

 

TAKING TESTING TO THE NEXT LEVEL:

If you are on this site before you ever step foot into a RE’s office, these are some things to ask about.

If you have not had success in trying thus far, maybe ask about these things in your follow up appointment.

Levels that can be tested through blood work:

  • Hemoglobin A1C: for people with PolyCystic Ovarian Syndrome, insulin resistance can affect the reproductive function of the ovaries.  HgbA1C assesses glucose levels and is a marker for insulin resistance.  Medication such as metformin can be used for people with insulin resistance to make them more sensitive to ovulation inducing medications
  • Testosterone: if you have hair on your face, belly button or nipples (like many women of Ashkenazi heritage have) ask to get this level checked.
  • TSH – Thyroid: your thyroid levels need to be in a certain range to be optimal for pregnancy. If they are not, you simply will have to take a pill to regulate it.

Procedure to ask about:

  • Endometrial biopsy: this is a biopsy of your endometrial lining, where an embryo would implant. If the area is infected, called endometritis, you may have to take antibiotics, or the doctor may want to give you a fresh lining and do a suction d&c. This protocol is used in Israel http://www.ivf-worldwide.com/ivf-worldwide-blog/endometrial-biopsy-improves-implantation-pregnancy-outcome.htm. (Not many practices in the U.S. do this, but I asked my doctor about it and we ended up using it in my protocols. Part of being your own advocate and asking questions.)

 

The number of possible tests is endless.  Sometimes a diagnosis is achieved (female factor infertility, male factor infertility, or combination male-female factor infertility)  and a targeted treatment plan mapped out.   Sometimes no diagnosis is ever received (unexplained infertility) but at some point the doctor will cease testing and proceed with a treatment plan, despite not knowing exactly what is being treated.

 

PART 3: POSSIBLE TREATMENT PROTOCOLS

Note: I have purposely not divided this list according to diagnosis. A couple may experience “female factor” infertility (with a variety of possible causes), “male factor” infertility,  a combination of both, or unexplained infertility.   Many of these treatments may be employed for any of these categories.

 

Clomid Cycle

Clomid is used to help women who may have ovulation issues,. If you are diagnosed with Polycystic Ovarian Syndrome (PCOS) you may be asked to do a clomid cycle. Clomid causes the pituitary gland to release hormones needed to stimulate ovulation (the release of an egg from the ovary).If you are having ovulation issues (which can be checked simply with a blood test on day 21 of your cycle) clomid may  be able to stimulate ovulation.  50mg is the typical starting dose for clomid, but patients who do not respond to this dose may receive 100mg or even 150mg.   Patients can either have intercourse at home after an ultrasound is performed to check for response, or an IUI can be performed.  Clomid can also help a woman who ovulates one egg every month to ovulate 2, 3, or 4, to increase her chances in any given month.   For patients under 35 years old, the risk of twins is approximately 5-10%, and the risk of triplets is 1 in 300-500.

Timed Conception

This is when a woman may or may not take hormone shots or ingestible hormones  to increase the number of follicles (which become eggs) and will be closely monitored between blood and ultrasound starting on day 2 or 3 of her cycle. When the follicles are the appropriate size, the woman will take a “trigger shot” (likely a medicine called ovidrel (recombinant hcg) at a very specific time to trigger ovulation. 36-40 hours later, the eggs will be released from the follicle and it is the optimal time to have intercourse.

 

IUI (Intrauterine Insemination) : Natural cycle or hormone assisted

An IUI is a procedure where the doctors take semen, that has been spun in a centrifuge, and inserted in a catheter which will be placed all the way up your vaginal canal, through the cervix,  into your uterus. This way when the eggs are released for ovulation, the sperm do not have to swim anywhere, they just need to find one egg and fertilize it. This procedure is typically done for mild male factor (with or without a female factor present as well) or unexplained infertility.

  • Steps for this procedure
    • Cycle day 2 or 3 come in for bloodwork and monitoring and if doing a hormone assisted cycle, you will begin taking prescribed hormones that night (for injectables you will likely be given gonal-f or follistim, low dose HCG, or menopur and for oral medication  you will likely be given clomid)
    • If you are or are not taking hormones, you will be instructed to come in for “morning monitoring” where they will take blood to check your progesterone and estrogen levels and some days you will get an ultrasounds to see how the follicles are growing.
    • TRIGGERING OVULATION:
      • FOR NATURAL CYCLE: they will either ask you to take ovulation predictor kits to let them know when you naturally ovulate and you will come in for your IUI the next day
      • HORMONE ASSISTED OR ANOTHER NATURAL CYCLE OPTION: Once the follicles and hormone levels are deemed “just right” you will get a call from your nurse with instructions on when to take your “trigger shot.” In this case, both natural cycles and hormone assisted patients both take the trigger. The shot will trigger ovulation of the eggs. If you are instructed to take the shot at 10pm, the likelihood is your IUI will be scheduled for 10am 2 days following.
    • Two mornings (36 hours) after you take the trigger shot, you will come in with your husband and either gather a semen sample in the office, or at home (this needs to be discussed with your doctor ahead of time if preparing sample at home)
      • If preparing the sample at home you need to make sure to deliver it to the lab within one hour of ejeculation. Make sure to keep the sample warm, DO NOT refrigerate.  A good way to do this is to keep it close to your body under your clothing as you emit heat or you can wrap it in a towel.
    • The  Andrology Lab will take the semen sample and spin it in a centrifuge. This will spin all the healthy and robust sperm to the bottom, and slower ones to the top. It is cleaning the sperm for you.
    • Once completed, they will check your identification to be sure they are giving you the right sample. Your sample will be in a vial for you to carry to your exam room.
    • Once in the exam room, you will be told to undress from the waist down, and wait for the doctor or nurse to come in and put the sample in the catheter. He/She will insert the catheter up your vaginal canal into your uterus and insert the sperm there.
    • They will remove it, and tell you to sit with your legs up or down and relax for 20 minutes.
    • You then wait 2 weeks to take a blood pregnancy test.

In-Vitro Fertilization (I.V.F.)

I.V.F. is a procedure where a woman takes hormones to stimulate the production of follicles in her ovaries. Once the follicles are the appropriate size she will inject a “trigger shot” to mature the eggs inside the follicles. It is very important to take this injection at the exact time your doctor instructs as this is timed for optimal retrieval. You will also be instructed to stop eating at a certain point the night before the retrieval because  on the day of your retrieval you will undergo anesthesia while the doctors physically retrieve the eggs from the follicles. They will then do a count of the number of eggs, how many were mature, and then fertilize them one of two ways, either natural fertilization or ICSI (to be explained soon) . Prior to fertilization they will also “wash” the semen sample to get the best sperm ready for fertilization.

DIFFERING I.V.F. PROTOCOLS

  • Antagonist  protocol: protocol that you would take an antagonist medication (like garilenix) to stop your body from ovulating until the doctors decide the follicles are ready)
  • Long agonist protocol: a cycle in which you would take lupron to shut down your brains reproductive hormones prior to starting IVF medications with the period after you’ve started the GnRH agonist
  • Agonist “flare” protocol: the GnRH agonist is started with the start of the period/IVF injections, causing an initial burst of reproductive hormones from the brain
  • Estrogen priming protocol: a pre-treatment for antagonist protocols in which the follicles are “synchronized” with estrogen prior to the start of injectable medications, which can be helpful for patients with low ovarian reserve

DIFFERING FERTILIZATION TECHNIQUES

  1. “Naturally Occurring” Fertilization: The embryologist will choose the “best looking sperm,” placing about 10,000 sperm in each culture dish with an egg. The culture dishes are kept in a special incubator, and after 12 to 24 hours, they are inspected for signs of fertilization.

 

  1. Fertilization Through I.C.S.I: if there is a severe male-factor infertility issue (like the sperm count is very small, or there are  many abnormal heads and tails in the sperm sample) this procedure will circumvent the problem*.  I.C.S.I stands for IntraCytoplasmic Sperm Injection , which means embryologist will choose ONE healthy-looking sperm and directly fertilize the egg with the sperm using a special thin needle. Note that some practices will routinely perform I.C.S.I. with an IVF cycle even when there is no male factor.

*I.C.S.I solving male factor issues: if the male has a low sperm count, you technically  only need as many sperm as eggs… so if the female makes 5 eggs, she only needs 5 sperm to fertilize.  I.C.S.I may not be necessary if the male factor is not severe (but too severe for IUI).   The doctor will be able to discuss his/her recommendation.

Depending on your clinic, you should receive a call within the next 24-28 hours with the total number of eggs that were fertilized. After fertilization occurs, you will have to wait 3 or 5 days, depending on your RE’s offices protocols, to find out how many embryos are available  for transfer. THIS MAY BE A QUESTION YOU WANT TO ASK BEFORE CHOOSING THE RIGHT PRACTICE.

  • Day 3 transfer: some offices feel that it is best to let the embryos grow in the natural host environment (the female) and therefore wait until day 3 at the “cleavage stage” when the cells have divided to about  6-10 cells and then transfer the embryo into the female. The procedure of transfer is similar to an IUI, a catheter with the  embryo  is inserted into your uterus and released there. Implantation will only occur 3-4 days later when a non-ART assisted embryo would reach the uterus from the fallopian tubes.
  • Day 5 transfer: other offices feel it is best to get the embryo to a healthy blastocyst stage where the embryo has begun to differentiate cells between what will be the placenta and what will be the fetus. The procedure of transfer is similar to an IUI, a catheter with  the embryo is inserted into your uterus and released there. Implantation would occur on either day 6 or 7.
    • If your embryos are NOT at the blastocyst stage on day 5, but are called “morulas” it means the cells have not organized yet. They may need a day or two more, but can still be transferred if they reach the blastocyst stage by day 6 in the morning. If they become “blasts” at day 6 in the afternoon, or even day 7, they will be frozen for another time. Research has shown that a woman’s uterine lining is most optimal for implantation on day 5, and diminished by day 6. You dont want to risk your lining no longer being optimal as you have come this far.

After the transfer you will have to take progesterone supplements in order to aid in keeping your progesterone levels high. In pregnancy, you would have high progesterone levels. You will either be given vaginal suppositories or gels or P.I.O. (progesterone in oil) shots. If pregnancy is successful, you may have to do this until the end of your first trimester, depending on your practice.

  • If you are given the PIO, please see our “Insider’s Guide to PIO Injections” page.

I.V.F. with P.G.S./ P.G.D./C.C.S.

P.G.S./P.G.D. or C.C.S. stands for  Preimplantation Genetic Screening, Preimplantation Genetic Diagnosis or Comprehensive Chromosome Screening. This is an amazing technology for a number of reasons. It allows the doctor’s office to remove ONE CELL from a day 3 embryo or approximately 10 cells from a day 5 embryo (depending on the office) and screen it for any number of reasons. I will highlight two here:

  1. If both member of the couple are carriers for a genetic disease (for example tay sachs) you would use PGD and would be able to find out if each embryo has tay sachs before transferring it.
  2. If there have been multiple miscarriages that were as a result of “abnormal embryos” either based on age or undetermined reasons they would perform PGS to test for overall chromosomal abnormalities, and you can help relieve the burden of another miscarriage by only selecting “normal embryos.”
  • If you are planning on doing P.G.S., P.G.D. or C.C.S. you may want to look for a practice that does day 5 transfers since there are more cells to chose from when removing a cell for testing. It would seem the embryo is more stable at the “blast” stage with more cells to chose from. If you chose a practice that does day 3 transfers, I would ask them to explain the stability of an embryo at the “cleavage” stage. (Very few practices would do day 3 biopsies anymore, and the proclivity of a clinic to offer day 3 transfers really doesn’t have much to do with how they would address PGD or PGS cycles.)
  • There is a WONDERFUL video all about P.G.D. from 60 minutes in 2014 http://www.cbsnews.com/news/breeding-out-disease-with-reproductive-genetics/

F.E.T. (Frozen Embryo Transfer)

This procedure is done if you have embryos that have been frozen. You could have frozen embryos for a number of reasons, some (not all) are listed below.

  • A previous retrieval yielded more embryos than you could use at that time- you had some “left over” for the future.
  • If you are enrolled in a “money saving” banking program that allows you to test up to 15 embryos before retrieval, you would “bank” all your embryos before transferring them.
  • For people at a practice with a day 5 transfer, if the embryo wasn’t fully at the blast stage, but rather something called a “morula” stage on day 5, but hit the blast stage on day 6, your lining would no longer be able to accept the embryo for healthy implantation, so you wait until the next cycle to implant it.
  • Sometimes, due to risk of hyperstimulation from the stimulating drugs, a woman may be advised to give her ovaries a “rest” in between retrieval and embryo transfer.  Embryos will be frozen until the doctor deems it safe to do a transfer.
  • PGD (see above) needs to be performed on the embryos.

If you are using frozen embryos, there are different methods for your cycle, you can either do a natural cycle that follows your typical ovulation schedule or you can do a medicated cycle. If your doctor performs a medicated cycle you might be given an injection  to prevent your body from creating new follicles and just priming your lining to be the best landing point for the embryo to implant. Some clinics will also do a programmed cycle with estrogen treatment but without a gnrh antagonist to  shut down the reproductive hormones from the brain. The F.E.T. is less expensive since you are only paying for monitoring (blood AND ultrasound to make sure your lining is FLUFFY – a “triple stripe”) and transfer, which is similar to an IUI procedure.  (However, under some insurance plans that only cover a set amount of treatments, it counts as a full treatment just like a full IVF, which includes both retrieval and transfer.)

QUESTIONS ABOUT FREEZING EMBRYOS

Cryopreservation vs. Vitrification

Before choosing an I.V.F. practice, do some research on how they freeze their embryos. The old technique is cryopreservation that entail a slow cooling of embryos until they finally freeze, however, sometimes this approach causes ice crystals to form inside the cells, and damaging the embryo. More recently a technique called vitrification, this freezes the embryo faster, so fast that there is not time to have crystals form, thus not damaging the embryo and increasing the embryo’s chance of surviving the thawing out process.

 

QUESTIONS ABOUT NUMBER OF EMBRYOS TO TRANSFER WITH IVF/FET:

How many embryos should you transfer in a given IVF cycle or FET? One? Two? More? Different practices/doctors have different leanings, and of course it will depend on the woman’s age,  individual medical and treatment history, and  likelihood of successful implantation.  The trend now in many practices is toward avoiding multiple gestations (often including twins).  Because of this, some practices are increasingly recommending IVF (in which there is near-total* control over the maximum number of embryos in a resulting pregnancy) in place of other treatments involving stimulating drugs without IVF (such as IUI).  Please discuss this issue with your doctor early on- don’t wait until the last minute before an embryo transfer to decide how many embryos to use!

*I say “near-control” because there is always a slight chance that a single embryo will spontaneously divide into identical twins.

In Conclusion:

I know this may seem like a lot of information, but it is a good thing to research a little before going to the doctor so that you may have some background, or a basis from which to ask questions when getting there. Make sure to “make nice” and become a true partner with your doctor and the nurses since you will speak with them often about questions. Apologize for being a pest in advance… its an expensive experience and difficult emotionally. You want them  on your team, but it is important to  – SPEAK UP – you are your own best advocate.

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