Fertility Challenges Causes & Concerns Getting Pregnant With Unexplained Infertility By Rachel Gurevich, RN Rachel Gurevich, RN Facebook LinkedIn Twitter Rachel Gurevich is a fertility advocate, author, and recipient of The Hope Award for Achievement, from Resolve: The National Infertility Association. She is a professional member of the Association of Health Care Journalists and has been writing about women’s health since 2001. Rachel uses her own experiences with infertility to write compassionate, practical, and supportive articles. Learn about our editorial process Updated on February 22, 2021 Medically reviewed Verywell Family articles are reviewed by board-certified physicians and family healthcare professionals. Medical Reviewers confirm the content is thorough and accurate, reflecting the latest evidence-based research. Content is reviewed before publication and upon substantial updates. Learn more. by Leyla Bilali, RN Medically reviewed by Leyla Bilali, RN Leyla Bilali, RN is a registered nurse, fertility nurse, and fertility consultant in the New York City area. She works in house at a reputable private clinic in New York City while also seeing her own clients through her concierge fertility consulting and nursing services business. Learn about our Medical Review Board Print Unexplained infertility doesn't mean there's no solution. In fact, there is reason for hope. Image taken by Mayte Torres / Getty Images Table of Contents View All Table of Contents Treatment Options Lifestyle Changes Trying Without Treatments Should You Keep Trying? Clomid IUI and Fertility Drugs IVF Other Options What is the best way to get pregnant if you’re facing unexplained infertility? While there’s no straightforward answer, typically, when you can’t get pregnant, the first step is fertility testing. Then, once a cause (or causes) is found, an appropriate treatment is pursued. If you’re not ovulating, Clomid may be tried. If sperm counts are low, IUI or IVF may be recommended. But what do you treat when your doctor doesn’t know what’s wrong? Treatment Options Unexplained infertility is treated empirically. This means a treatment plan is based on clinical experience and some guesswork. The most common treatment map for unexplained infertility looks like this: Lifestyle changes recommended (like weight loss, quitting smoking) Continue to try on your own (if you’re young and willing) for six months to a year Clomid or gonadotropins along with IUI for three to six cycles IVF treatment for three to six cycles Rarely, third-party IVF treatments (like using an egg donor or surrogate) Sometimes, in cases of ongoing unexplained infertility beyond basic IVF, somewhat controversial treatments are considered. Below is a closer look at each of these approaches and the odds of pregnancy success. Lifestyle Changes Especially when the cause of infertility is unknown, improving your overall health is important. The most commonly suggested lifestyle changes to improve your fertility naturally are to: Avoid excessive alcohol consumption. Cut back on caffeinated drinks. Lose weight (if overweight) and exercise. Reduce overall stress. Quit smoking. With all that said, there’s no research showing that making these changes can actually help you conceive. However, these factors are associated with decreased fertility. That’s important to know. Given the shot-in-the-dark approach to unexplained infertility treatment, whatever lifestyle changes you and your partner make to improve your overall health for the better can’t hurt and may help. Trying to Conceive Naturally You likely don’t want to hear from your doctor that the first step is to “keep trying on your own” for another six months. However, in some cases, it may be a good plan. (But only after testing has confirmed your diagnosis as unexplained. It’s not a good idea to keep trying on your own before you’ve both been tested since some causes of infertility worsen with time.) Expectant management is when your doctor doesn’t prescribe treatments right away, but does conduct basic fertility testing and may monitor the situation as you try on your own for a limited time. A randomized clinical trial was conducted comparing expectant management (for couples with a good prognosis) with IUI plus fertility drugs. The study took place over a six-month period. For the women who received IUI plus fertility drugs: 33% of the women achieve pregnancy23% of the pregnancies were on-going at study’s end For the women who didn’t receive treatment and went the expectant management route instead: 32% got pregnant on their own27% of the pregnancies were on-going at study’s end So, IUI plus fertility drugs for those with good prognosis didn’t improve their odds of pregnancy success. The couples that kept trying on their own were just as likely to conceive as those who received treatment. Given treatment costs, fertility drug risks, and the increased risk of a multiple pregnancy, trying on your own for a limited period of time may be the best choice. Building on this research, another study looked at what happens when couples are assigned a treatment plan based on prognosis. (Their prognosis was determined by looking at their age and how long they’ve been trying to conceive on their own.) In this study, couples were assigned to one of three paths: start with expectant management, start with IUI with fertility drugs, or go straight to IVF treatment. A little over 90% of the couples were assigned to the expectant-management-first group. By the study’s end, 81.5% of couples achieved pregnancy. Of those pregnancies, 73.9% were conceived without fertility treatment. Those are excellent odds, especially when you consider success rates for infertility in general. When looking at all infertility causes and cases, live birth rates after treatment are just under 50%. Should You Keep Trying? As always, discuss your options with your doctor. Both of the studies above only included couples with a good prognosis. They were on the younger side and had not been trying for years. Generally speaking, expectant management for six months to a year is only a good approach if: A through fertility workup has been conducted, with both male and female fertility tested. (The diagnosis should truly be “unexplained.”) Ovarian reserve testing (FSH, AMH, and antral follicle counts) looks good. You have tried for less than one to two years on your own. You’re age 35 or younger. Is Clomid a Good Choice? Clomid is the most commonly prescribed fertility drug, and it can help women who are not ovulating. It can also boost sperm production for some causes of male infertility. The first doctor you will see when trying to treat your infertility is your gynecologist. They are most likely prescribe you Clomid, even if you have unexplained infertility, and send you on your way. This may be a waste of time and expose you to risks and side effects for no benefit. A randomized control trial in Scotland included 580 women with unexplained infertility. The women were randomized to one of three groups for six months of treatment: Clomid treatmentExpectant managementIUI alone (no fertility drugs) The live birth rate for each group was: 13% percent for Clomid17% for expectant management22% for IUI treatment It’s interesting to note that live birth rates using Clomid were slightly lower than expectant management, and this makes sense. Clomid side effects actually reduce some aspects of your fertility. A meta-analysis of several randomized control trials of Clomid for unexplained infertility considered the results of seven different studies. A total of 1,159 couples were included in this study. This study also found that there is no evidence that Clomid alone is an effective treatment for unexplained infertility. Clomid treatment is not harmless. Treatment is also only recommended for up to six cycles, due to the possible increased risk of cancer. If your doctor suggests Clomid alone, discuss whether it would be better to continue trying on your own for awhile longer, or discuss whether they would consider moving straight to IUI with Clomid. This may require moving onto a fertility clinic and reproductive endocrinologist. Few gynecologists are comfortable or experienced at administering IUI treatment. IUI and Fertility Drugs For those with unexplained infertility, IUI alone or with fertility drugs has been shown to slightly increase your odds of pregnancy. The evidence isn’t very strong. However, due to the very high cost and invasiveness of IVF, IUI with fertility drugs is worth trying. For unexplained infertility, Clomid with IUI seems to be the preferred choice over IUI with gonadotropins. In a randomized control study, couples were randomized to three cycles of IUI and Clomid, or IUI with gonadotropins, or IVF. The pregnancy rates were: 7.6% per cycle for Clomid with IUI9.8% per cycle for gonadotropins with IUI30.7% per cycle for IVF Gonadotropins are more expensive and are more likely to lead to ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy. But they may not improve pregnancy rates enough to justify those risks. How many cycles of IUI should you try? This depends on your age and your interest in pursuing IVF treatment if IUI should fail. For those that are open to IVF, three cycles of IUI with Clomid is likely a good enough trial before moving onto IVF. According to the same study mentioned above, couples who tried IUI with gonadotropins before moving onto IVF took longer to get pregnant and spent more money on treatment overall. For those that are not willing or able to pursue IVF treatment, research shows IUI with fertility drugs are worth trying for up to nine cycles. When to Use IVF When it comes to treating unexplained infertility, IVF has the best odds for pregnancy success. The pregnancy rates for IVF treatment are three times what they are for IUI with Clomid. This will vary with age, however. As mentioned above, the pregnancy rate for Clomid with IUI is 7.6%. The pregnancy rate per cycle for IVF is 30.7%. Not only are the success rates higher for IVF, the cause of the “unexplained” infertility is sometimes discovered during treatment. Only during IVF can egg quality, the fertilization process, and embryo development be observed closely. All that said, IVF is invasive and expensive. You might think going straight to IVF is the best choice (given it’s superior success rates). It is actually better for the vast majority of couples to give IUI with Clomid a try first. Most insurance companies (that offer any sort of IVF coverage) require less expensive treatments to be attempted first. However, proceeding straight to IVF and skipping IUI may be the best choice if you’re age 38 or older. This is something to discuss with your doctor. What Are Your Chances of Getting Pregnant After 35? Beyond IVF What if IVF alone isn’t enough? Or what if traditional IVF fails? There may be other options. Reproductive Immunological Treatments There is a theory that natural killer cells may play a role in unexplained infertility, repeated IVF failure, or recurrent miscarriage. Despite their name, “natural killer cells” aren’t bad. You want them. You just don’t want them to be overly reactive or have too many of them. Intravenous infusion with a substance known as intralipids during IVF treatment may reduce the impact of excessive natural killer cells. However, there’s currently no strong evidence this treatment can improve IVF live birth rates. Removal of Endometrial Deposits Some believe that unexplained infertility may be caused by mild endometriosis. In this case, the endometrial deposits may not be causing pain or directly interfering with ovulation or the fallopian tubes, but their presence may increase “irritation” of the reproductive system. This may be the cause for repeated IVF failure, according to this theory. Some doctors will suggest laparoscopic surgery to diagnosis and remove mild endometriosis before IVF is attempted. Others only suggest it after repeated IVF failure. Whether this treatment can improve live birth rates isn’t clear. Gamete Donation If egg, sperm, or embryo quality problems are discovered during IVF, your doctor may recommend using a gamete or embryo donor for your next IVF cycle. Egg donation is the most expensive option, followed by embryo donation, and then sperm donation. Success rates for egg donors are generally high, which is good news. Embryo donation rates will vary depending on the source of the embryo. For example, many embryo donations come from extra embryos created for another infertile couple’s IVF treatment. Surrogacy If IVF treatment repeatedly fails after embryo transfer, surrogacy may be the next step. Surrogacy is extremely expensive and not (easily) legally available in all areas. For those that can afford and access surrogacy services, it can be their path the parenthood. 12 Questions to Ask If You Think You're Infertile Was this page helpful? Thanks for your feedback! Get diet and wellness tips to help your kids stay healthy and happy. Sign Up You're in! Thank you, {{form.email}}, for signing up. There was an error. Please try again. What are your concerns? Other Inaccurate Hard to Understand Submit 10 Sources Verywell Family uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy. Sharma R, Biedenharn KR, Fedor JM, Agarwal A. Lifestyle factors and reproductive health: taking control of your fertility. Reprod Biol Endocrinol. 2013;11:66. doi:10.1186/1477-7827-11-66 Best D, Avenell A, Bhattacharya S. How effective are weight-loss interventions for improving fertility in women and men who are overweight or obese? A systematic review and meta-analysis of the evidence. Hum Reprod Update. 2017;23(6):681-705. doi:10.1093/humupd/dmx027 Pandian Z, Gibreel A, Bhattacharya S. In vitro fertilisation for unexplained subfertility. Cochrane Database Syst Rev. 2015;(11):CD003357. doi:10.1002/14651858.CD003357.pub4 Brandes M, Hamilton CJ, Van der steen JO, et al. Unexplained infertility: overall ongoing pregnancy rate and mode of conception. Hum Reprod. 2011;26(2):360-8. doi:10.1093/humrep/deq349 Bhattacharya S, Harrild K, Mollison J, et al. Clomifene citrate or unstimulated intrauterine insemination compared with expectant management for unexplained infertility: pragmatic randomised controlled trial. BMJ. 2008;337:a716. doi:10.1136/bmj.a716 Hughes E, Brown J, Collins JJ, Vanderkerchove P. Clomiphene citrate for unexplained subfertility in women. Cochrane Database Syst Rev. 2010;(1):CD000057. doi:10.1002/14651858.CD000057.pub2 Reindollar RH, Regan MM, Neumann PJ, et al. A randomized clinical trial to evaluate optimal treatment for unexplained infertility: the fast track and standard treatment (FASTT) trial. Fertil Steril. 2010;94(3):888-99. doi:10.1016/j.fertnstert.2009.04.022 Bashiri A, Halper KI, Orvieto R. Recurrent Implantation Failure-update overview on etiology, diagnosis, treatment and future directions. Reprod Biol Endocrinol. 2018;16(1):121. doi:10.1186/s12958-018-0414-2 Tanbo T, Fedorcsak P. Endometriosis-associated infertility: aspects of pathophysiological mechanisms and treatment options. Acta Obstet Gynecol Scand. 2017;96(6):659-667. doi:10.1111/aogs.13082 Aflatoonian N, Eftekhar M, Aflatoonian B, Rahmani E, Aflatoonian A. Surrogacy as a good option for treatment of repeated implantation failure: a case series. Iran J Reprod Med. 2013;11(1):77-80. Additional Reading Brandes M1, Hamilton CJ, van der Steen JO, de Bruin JP, Bots RS, Nelen WL, Kremer JA. “Unexplained Infertility: Overall Ongoing Pregnancy Rate and Mode of Conception.” Hum Reprod. 2011 Feb;26(2):360-8. doi: 10.1093/humrep/deq349. Epub 2010 Dec 16. 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. Hughes E1, Brown J, Collins JJ, Vanderkerchove P. “Clomiphene Citrate for Unexplained Subfertility in Women.” Cochrane Database Syst Rev. 2010 Jan 20;(1):CD000057. doi: 10.1002/14651858.CD000057.pub2. Reindollar RH1, Regan MM, Neumann PJ, Levine BS, Thornton KL, Alper MM, Goldman MB. “A Randomized Clinical Trial to Evaluate Optimal Treatment for Unexplained Infertility: the Fast Track and Standard Treatment (FASTT) Trial.” Fertil Steril. 2010 Aug;94(3):888-99. doi: 10.1016/j.fertnstert.2009.04.022. Epub 2009 Jun 16. Wordsworth S1, Buchanan J, Mollison J, Harrild K, Robertson L, Tay C, Harrold A, McQueen D, Lyall H, Johnston L, Burrage J, Grossett S, Walton H, Lynch J, Johnstone A, Kini S, Raja A, Templeton A,