Taking Next Steps After Failed Fertility Treatment

How Many Times to Try and What's Next After Clomid, IUI, and IVF Failure

Hispanic woman looking at a negative pregnancy test with tissues in her hand
Jose Luis Pelaez Inc / Blend Images / Getty

Whether it’s your first Clomid cycle or your fourth IUI, a failed fertility treatment cycle feels terrible. Any cycle that doesn’t lead to pregnancy can feel bad. That said, when you’ve invested emotional energy, time, and money, your hopes are higher. Higher hopes mean more frustration when things don’t go as planned.

The good news is that with persistence and the right treatment plan, most couples can eventually get a baby.

The bad news is it will likely take time... and it can get expensive. 

Can you get pregnant on your first try? Yes, sometimes. Keep in mind, though, that even people with naturally good fertility aren’t guaranteed a quickly conceived pregnancy. Depending on your prognosis and which fertility treatments are suggested, going through several cycles may be necessary.

What should you do after a failed fertility treatment cycle? How do you know if you should move onto another treatment or when to keep trying with the same protocol? Here’s what the research has to say.

Art + Science: Fertility Treatment Not the Same Path for Everyone

When speaking about fertility treatment, it’s commonly assumed that everyone’s fertility treatment path looks like this: first Clomid, then IUI with injectables, then IVF. However, it’s more complicated than that.

First of all, almost every treatment modality has “additions” that may be adjusted or added on.

For example, Clomid can be tried alone. Or, it may be used along with metformin, baby aspirin, progesterone, IUI, or a trigger shot of hCG. Or your doctor may switch you from Clomid to letrozole. These changes or additions may be used right from the start, or your doctor may adjust plans later.

Secondly, not every person should start at Clomid.

For some, going straight to IUI or even IVF is the best option. If, for example, you have blocked fallopian tubes or severe male factor infertility, IVF may be your only option. "Trying" Clomid first may make no sense at all.

Thirdly, sometimes a treatment is tried that is unlikely to succeed—but you decide as a team to try it a few times anyway. For example, let’s say a woman has primary ovarian insufficiency. Let’s say her doctor knows IUI with injectables has low odds for success in her situation, but the couple wants to try a couple of times before IVF. They may decide this because they don’t have funds for IVF (and therefore IUI is their only practical option), or maybe their insurance coverage requires trying IUI first. The number of insemination cycles to attempt before moving on may be completely different from a couple for which IUI comes with a better prognosis.

Keep all this in mind as you review the guidelines below.

When Clomid (or Letrozole) Treatment Fails

Clomid, also known as clomiphene citrate, is the most commonly prescribed fertility drug. Letrozole is not a fertility drug by design (it’s actually a cancer drug), but it works a lot like Clomid. Letrozole may be better for women who don’t ovulate on Clomid or for women with PCOS.

For female factor infertility with mild to moderate ovulation problems, Clomid can be successful. When ovulation problems are the only difficulty, the pregnancy success rate reaches 60 percent after six cycles.

For those who will get pregnant on Clomid, most will conceive in the first three months. About 71 to 87 percent of pregnancies conceived with Clomid occur by try number three.

How many cycles should you try before moving on? Between three to six cycles seem to be the suggested range. Beyond cycle six, few pregnancies occur.

In fact, with Clomid, having more than six cycles is discouraged. Some studies have found an increased risk of certain cancers if Clomid is used more than six times without a pregnancy success.

 

What if Clomid (or Letrozole) doesn’t work after three to six cycles? Injectables with IUI are usually next.

When Injectables/Gonadotropins or IUI Fail

Gonadotropins are injectable fertility drugs. They may be used alone to stimulate ovulation, and then the couple has sexual intercourse timed for ovulation to conceive. Or, they may be used along with intrauterine insemination (IUI). Because gonadotropins are already expensive, and IUI adds a small amount more to that expense while slightly boosting the odds for pregnancy success, most doctors combine IUI and gonadotropins therapy.

IUI may also be recommended in cases of mild male infertility. In this case, fertility drugs may or may not be used along with it. IUI with gonadotropins may also be used in cases of unexplained infertility. Depending on the cause of infertility, success rates for IUI vary considerably, from a low 7 percent per cycle up to 20 percent.

What about when IUI fails? How many cycles should you try?

It’s often said that trying three cycles is a good enough trial, and that trying four or more isn’t worth it. However, this may not be the case. A large, research study looked at the ongoing and per cycle IUI success rates of 3,700 couples. It included over 15,000 IUI cycles, and couples were receiving treatment for either male infertility, cervical factor, or unexplained infertility.

Over three cycles, 18 percent conceived. After seven cycles, the on-going pregnancy rate was 30 percent. After nine, it reached 41 percent. The study found that the average per-cycle success rate was about 5.6 percent. The per cycle success rates for cycles number seven, eight, and nine were close to the average—5.1, 6.7, and 4.6 percent respectively. This means that success rates did not significantly drop after three tries.

They concluded that trying up to nine cycles of IUI with mild ovarian stimulation is reasonable. If IUI is not successful, IVF is often the next step. However, a couple may still decide after three IUI failures to move on. Here’s why.

First of all, every treatment cycle that fails brings an emotional toll. The more failed cycles a couple experiences, the more likely they may be to decide to stop trying altogether. The per cycle success rates are higher for IVF than IUI. If funds are available, and IVF is a reasonable next step, moving on may make sense.

Secondly, IUI is less expensive than IVF, but it’s not inexpensive by any means. It can cost between several hundred to a few thousand dollars per try, depending on insurance coverage and how many fertility drugs are needed to stimulate ovulation.

Going through several IUI cycles may mean less or unavailable funds for IVF.

The bottom line: If IVF is within reach, and you want to move on from IUI after three cycles, that may be a good choice. If IVF is not an option because of funds, or you just prefer to stay with IUI before moving on, trying up to nine cycles of IUI is reasonable.

When IVF Fails

IVF treatment may be recommended if the fallopian tubes are blocked, in some cases of male factor infertility, or if previous fertility treatments were unsuccessful. IVF treatment is invasive and expensive. According to one study, the average out-of-pocket expense for one cycle of IVF is around $19,000.

During conventional IVF, fertility drugs are used to overstimulate the ovaries, so they mature several oocytes, or eggs. Then, these eggs are retrieved with an ultrasound-guided needle through the vaginal wall. The eggs are put together with sperm (which is either received from a sperm donor or the male partner produces a sperm sample through self-stimulation.) Hopefully, some of the eggs become fertilized with the sperm, and some healthy embryos result. After three to five days, one or two embryos are transferred to the woman’s uterus.        

You can read about IVF treatment in more detail here.

Sometimes, an IVF cycle isn’t even able to reach embryo transfer. This is known as IVF cancellation. This is a slightly different situation from when an IVF cycle does get to embryo transfer but doesn’t result in pregnancy. You can read more about what’s next after IVF cancellation here.

When a cycle of IVF fails, it can be devastating, emotionally and financially. However, one failed IVF cycle doesn’t mean it won’t succeed the next time.

In fact, for couples that do conceive, it takes an average of 2.7 cycles to achieve pregnancy.

Success rates are better for younger women, but even then, several cycles may be required. One study of over 178,000 linked cycles found that the cumulative live birth rate after three cycles was 42.3 percent. After eight cycles, the cumulative live birth rate was 82.4 percent.

What happens when IVF doesn’t result in pregnancy?

“Unfortunately, regardless of the age of the patient, many IVF cycles are unsuccessful,” says Dr. Michael C. Edelstein of Virginia Fertility Associates.

“After such a cycle, I believe it is important for the physician to review with the patient the events of the unsuccessful cycle to see if any adjustments can be made in the next attempt,” explained Dr. Edelstein. “Candidly, in many cases, no changes are indicated, and the best option is to proceed again. Physicians understand that often many attempts may be necessary.”

What kind of adjustments may be made? IVF treatment can be altered or enhanced with a variety of additional assisted reproductive technologies. Many times trying again with the same protocol makes sense. But sometimes, additional technologies or medical adjustments should be made.

Examples include:

  • Different medication protocols
  • Genetic screening like PGD/PGS
  • Immunotherapy
  • Adding in ICSI (which can aid in fertilization of the eggs)
  • Assisted hatching (which may help with implantation)

How many cycles of IVF should you be open to trying? Research has found that trying up to six times can be worthwhile. One study found that the cumulative live-birth rate after six cycles was 65.3 percent.

Six cycles, however, can be cost prohibitive for many people. This is why some fertility clinics offer refund or shared risk programs to couples with a good prognosis. This is when you pay an upfront fee for several cycles. If you don’t get pregnant, you get back some of your money.

Dr. Edelstein explains how this works at his clinic. “In the Shared Success/Money Back Guarantee Program of my own IVF Center, with our good prognosis patients we allow six fresh cycles and unlimited frozen cycles, and if a baby is not brought home, the patient receives a 100 percent refund of all money paid to the IVF program.”

When Egg Donor Treatment Fails

Egg donor IVF may be recommended in cases of primary ovarian insufficiency (premature ovarian failure), low ovarian reserves (more common in women over age 38), or poor egg quality during previously failed or canceled IVF cycles.      

Egg donor IVF is extremely expensive, costing as much as $25,000 to 30,000 per egg retrieval cycle. However, it has excellent success rates, better than conventional IVF even for couples with the best prognosis.

“The preliminary data of the 2015 report of the Society of Assisted Reproductive Technology (SART) gives a live birth rate of 50.4 percent per attempt from almost 6000 cycles reported that year,” says Dr. Edelstein.

That said, 50 percent isn’t 100 percent.

Explains Dr. Edelstein, “Even with this excellent success rate, 1 in 4 women will have two consecutive failures, and 1 in 8 will experience three.  In general, after two or three failures, it may make sense to repeat or do more testing on the recipient.”

Testing may include repeat or further hormonal blood work (especially checking thyroid and prolactin levels) and uterine evaluations, like saline sonohysterogram or hysteroscopy.

“There is some preliminary evidence that a special biopsy of the uterine lining called an Endometrial Receptivity Assay (ERA) can identify patients that may be having their embryos transferred on a day when the uterus is less receptive, and adjustments to the day of transfer may help,” says Dr. Edelstein. “Sometimes a biopsy of the lining of the uterine cavity can identify a chronic infection (endometritis) that can be treated.”

Testing, however, doesn’t always bring answers to why treatment has failed.

“Unfortunately, in many cases, no reason can be identified for the repetitive failure, and the best option would be another embryo transfer—and many patients do conceive on their fourth or fifth transfer cycle.”

When egg donor IVF fails, is gestational surrogacy the next step? Not necessarily.

In reference to surrogacy after IVF egg donor failure, Dr. Edelstein says, “This is obviously an expensive and complicated alternative that involves many emotional, financial, logistic, and legal issues.  Most couples do not quickly move to this option unless there is definite evidence that the intended mother's uterus has a major identifiable issue that is the cause of the repetitive failure with the transfer of embryos created with donor oocytes.” 

What Happens After a Failed Cycle: Regardless of the Treatment Option

Whatever treatment you’re having, you can expect that your doctor will discuss with you...

  • What went wrong: Sometimes it’s just a matter of trying again. But in cases of more complex treatments, like IVF, identifying where things fell through may help boost your odds of success next time.
  • What your odds for success are if you try again: Sometimes, they are just as good as the first time. Sometimes, especially after a few to several cycles, the odds of success decrease significantly on the next try.
  • Any possible risks of sticking with the same treatment: For example, Clomid should not be used for more than six cycles. Or, another example, doing repeat IUIs may be exhausting your emotional and financial reserves.
  • What additional testing may be recommended, if any: Sometimes it’s testing you’ve had before; sometimes it’s something new. For example, genetic screening, karyotyping, testing for reproductive immunology issues, or a more advanced uterine evaluation.  
  • What changes should be made, if any: Discussing additional risks, costs, and success rates when adding in these changes should also be explained.
  • What the next step would be if you move on.

In some cases, you may want to get a second opinion.

“Patients need to be comfortable with their physician and the IVF clinic he or she is associated with,” says Dr. Edelstein. “They should be able to have all their questions answered, have a good understanding of the procedures being performed, and a knowledge of realistic success rates.”

“However, there comes a point often—after three or four unsuccessful cycles—when a couple may question whether the process will ever work,” Dr. Edelstein continues. “This is understandable.”

“Sometimes a couple may request a second opinion from another physician.  I personally have no problem with this request and welcome it.  It most cases it validates what we are doing and sometimes it helps us learn something that can help in the next IVF attempt.   Only through openness and honesty on the part of the physician and the patient, can we have the best chance of achieving success.”   

A Word From Verywell

Coping with a failed fertility treatment cycle is not easy. Failed treatments take an emotional and financial toll. It’s normal to feel frustration and sadness.

That said, few people have success on their first or even second try. Remember that one or two failed cycles don't mean things will never succeed. You may just need more time or a different treatment plan.

That said, don’t be afraid to say “enough is enough” if you’ve reached that point. It’s easy for those on the outside to say, “Never give up.” But deciding to move on is not “giving up.”

Choosing a childfree life after infertility or pursuing adoption may be alternatives to continuing with treatments. You don’t have to try every treatment available before deciding to move on.

Be sure to seek out support from a counseling professional, a support group, or your friends and family while you navigate the fertility treatment arena, especially if you ultimately walk away without success. You don’t need to do this alone, and you shouldn’t. The more support you have, the better.

Sources:

Custers IM1, Steures P, Hompes P, Flierman P, van Kasteren Y, van Dop PA, van der Veen F, Mol BW. “Intrauterine insemination: how many cycles should we perform?” Hum Reprod. 2008 Apr;23(4):885-8. doi: 10.1093/humrep/den008. Epub 2008 Feb 8.

Homburg R1. “Clomiphene citrate—end of an era? A mini-review.” Hum Reprod. 2005 Aug;20(8):2043-51. Epub 2005 May 5.

Edelstein, Michael C. M.D. Virginia Fertility Associates. Email interview. November 15, 2017.

McLernon DJ1, Maheshwari A2, Lee AJ2, Bhattacharya S2. “Cumulative live birth rates after one or more complete cycles of IVF: a population-based study of linked cycle data from 178,898 women.” Hum Reprod. 2016 Mar;31(3):572-81. doi: 10.1093/humrep/dev336. Epub 2016 Jan 18.

Smith ADAC1,2, Tilling K1,2, Nelson SM#3, Lawlor DA#1,2. “Live-Birth Rate Associated With Repeat In Vitro Fertilization Treatment Cycles.” JAMA. 2015 Dec 22-29;314(24):2654-2662. doi: 10.1001/jama.2015.17296.

Stewart LM1, Holman CD, Hart R, Finn J, Mai Q, Preen DB. “How effective is in vitro fertilization, and how can it be improved?” Fertil Steril. 2011 Apr;95(5):1677-83. doi: 10.1016/j.fertnstert.2011.01.130. Epub 2011 Feb 12.

Continue Reading