Female factor infertility IVF success rates: PCOS, low ovarian reserve, endometriosis and more

Last Updated on March 12, 2020

Female infertility cause is a crucial factor in determining the IVF success rate. Women need functioning ovaries, uterus and fallopian tubes to become pregnant and carry a baby to term. Abnormalities with these reproductive organs could cause PCOS, low ovarian reserve, endometriosis and tubal abnormalities. These conditions contribute to different outcomes and risks during IVF treatments.

Polycystic ovary syndrome (PCOS) IVF success rates

PCOS is a cause of female infertility that affects 5-10% of women of reproductive age. Women with PCOS usually have irregular ovulation and menstruation, excessive androgen hormones and limited follicular development.

IVF is recommended to infertile patients who do not respond to PCOS treatment. However, not all PCOS patients have the same IVF success rates.

Firstly, PCOS is a heterogenous disorder that includes multiple phenotypes that are associated with different IVF outcomes.1

  • Phenotype 1: increased serum Anti-Mullerian Hormone (AMH) levels, oligo/amenorrhoea and clinical or biochemical hyperandrogenism
  • Phenotype 2: increased serum AMH levels and clinical or biochemical hyperandrogenism
  • Phenotype 3: oligo/amenorrhoea

Among them, phenotype 3 has normal androgen levels and the best IVF outcome. In contrast, PCOS patients with high androgen have significantly worse outcomes.

Phenotype 1 Phenotype 2 Phenotype 3
Live birth rate using fresh embryo transfer (%) 16.7% 18.5% 33.7%

Secondly, nearly half of all women with PCOS are also overweight or obese, which predisposes patients to worth IVF outcomes.2 Advanced maternal age also negatively affects pregnancy rate, which is a trend for all natural and IVF-assisted conception.

Pregnancy rate using fresh embryo transfer (%)
BMI/Age <35 ≥35
Normal weight (18.5 – 24.9) 42% 34.6%
Overweight (25 – 29.9) 43.6% 41.7%
Obese (≥30.0) 35.5% 22.6%

Thirdly, PCOS patients are at higher risk of hormone-related side effects and complications. Most patients (Phenotype 1 & 2) experience an existing hormonal imbalance due to excessive production of androgen hormones. In addition to this, an IVF cycle usually begins with controlled ovarian hyperstimulation using high doses of Follicle-stimulating hormone (FSH). Women with PCOS are more prone to develop severe ovarian hyperstimulation syndrome (OHSS). OHSS not only reduces the ability of fertilization and pregnancy, but also poses a life threat.

Therefore, the odds of success for PCOS patients depend on their phenotype, weight, age and risk of OHSS.

Low ovarian reserve IVF success rates

Ovarian reserve diminishes most consistently with a woman’s age because females are born with all the eggs she will ever have. It is associated with poor ovarian response to the first step of IVF treatment, controlled ovarian hyperstimulation. Therefore, patients with low ovarian reserve and poor ovarian response tend to produce few eggs suitable for IVF fertilization, leading to low success rates.

One large 15-year cohort study reported low live birth rate in patients with poor ovarian response.3 Note that the success rates are calculated after 6 IVF cycles, demonstrating the difficulty of pregnancy when the ovarian reserve is low. Normally, about two thirds of patients will be successful after 6 or more cycles of IVF. But women with low ovarian reserve has a mere 22% live birth rate when they are under 30. With advancing maternal age, the odds of success drop even more.

≤30 31-34 35-37 38-40 41-43 >43
Live birth rate (%) 22% 18.3% 17.2% 13.5% 10.5% 4.4%

* Includes both fresh and frozen cycles

Consistently, another study reported the lowest live birth rate when the infertility cause is low ovarian reserve, as compared to PCOS, endometriosis, tubal factors, uterine factors, and male factors.4

As such, women with low ovarian may experience disappointing outcomes with IVF treatment using their own eggs.

Endometriosis IVF success rates

Endometriosis is a chronic inflammatory condition affecting approximately 10% of women of reproductive age and up to 40% of infertile women. IVF outcomes are controversial for this group of patients as studies have shown mixed results.

There is evidence that patients with endometriosis could expect similar age-based IVF success rates as non-endometriosis patients, unless they also have poor ovarian reserve. In a recent case-control study, patients with endometriosis had a live birth rate (per transfer) of 39.3%, similar to those without the condition (37.9%).5

A number of studies suggest that endometriosis can decrease ovarian response and implantation in IVF cycles, but the odds of pregnancy and live birth are similar between women with isolated endometriosis (no other diagnosis) and women without endometriosis.5,6 Notably, even when women have ovarian endometrioma, their live birth rate is not reduced. When compared to women with tubal factor infertility, women with endometriosis have higher live birth rates using IVF.

However, other studies have shown less promising IVF outcomes in women with endometriosis. One recent study showed a negative impact of endometriomas on egg quality and ovarian reserve.7 Even after endometriomas are removed, there is sustained damage to ovarian reserve. When a woman has endometriosis as well as other infertility diagnosis, IVF success seems to decrease significantly.6

Despite mixed findings in the literature, IVF treatment may be worthwhile for treating women with endometriosis, especially when patients do not have other infertility factors.

Tubal factor IVF success rates

Tubal factor infertility is another common cause of infertility that contributes to 30-35% of female infertility. It mainly involves blocked fallopian tubes which prevent the egg from traveling down the tube for fertilization. Laparoscopic surgery was commonly used to treat the fallopian tubes. However, if repair surgery is unsuccessful, IVF treatments may help women with tubal factor conceive.

IVF outcomes for this group of patients largely depends on whether blocked fallopian tubes have created a hydrosalpinx (fluid that collects inside fallopian tubes). Pregnancy rates in the women with tubal infertility but no hydrosalpinx are 31.2%.8 In contrast, those have hydrosalpinx have a 19.7% chance of getting pregnant. Live birth rate decreases accordingly, whereas the risk of early pregnancy loss increases in the presence of hydrosalpinx.

Tubal factor with hydrosalpinx Tubal factor without hydrosalpinx
Pregnancy rate (%) 19.7% 31.2%
Live birth rate (%) 13.4% 23.4%
Early pregnancy loss (%) 43.7% 31.1%

Unfortunately, tubal factor infertility has also been associated with low live birth rate, increased risks of miscarriage, preterm birth and low birth weight upon delivery as compared to male infertility.9

After tubal ligation IVF success rates

Tubal ligation is considered a permanent form of birth control. However, it is possible to get tubal reversal surgeries. IVF is also effective to help women with previous tubal ligation conceive. Since tubal ligation operates on the fallopian tubes without affecting the ovaries, any women with a good ovarian reserve is a good candidate for IVF.

There is evidence that IVF success in women who had undergone tubal ligation is similar to other subfertile women (>30% for women under 40).10 The live birth rates are dependent on maternal age, as it is the most important predictor for IVF in any patient group.

How to improve female factor infertility IVF success

  1. Freeze-all strategy and frozen embryo transfer

Freeze-all strategy is when all retrieved eggs frozen for later embryo transfer without undergoing fresh embryo transfer. It effectively avoids OHSS, which is detrimental to both the patient’s health and IVF success. Women with PCOS are especially susceptible to developing OHSS. Performing frozen embryo transfers also provide a better endometrial environment that benefits embryo implantation. In women with advanced endometriosis, adopting the freeze-all strategy resulted in higher implantation, pregnancy and live birth rates compared to using fresh transfers.11

  1. In vitro maturation (IVM) to prevent OHSS

IVM involves collecting immature eggs that are cultured in vitro until they reach fertilization potential. Since collecting immature eggs do not require controlled ovarian hyperstimulation, it prevents OHSS in PCOS patients. A large retrospective study has shown a promising 30% live birth rate using IVM in PCOS patients.12

  1. Protocol personalization for different patient groups

Even within the same category of infertility cause, such as PCOS, women present with different phenotypes and hormonal profiles. Therefore, it is important to get personalized ovarian stimulation protocols from your fertility specialist.

There has also been a myriad of studies on improving IVF success rate in patients with low ovarian reserve, yet no consensus is reached about the treatment strategy. The recommendation is to consult a fertility specialist and optimize a treatment protocol that is tailored to your profile.

In patients with endometriosis, there is some evidence that prolonged course of GnRH agonist as well as Letrozole co-treatment may improve IVF outcome.13

In patients with tubal factor infertility, it is important to note whether hydrosalpinx is present. If it is, a salpingectomy prior to IVF has been shown to have a 2.4-fold increase in the IVF live birth rate.14

References

1 De Vos, M. et al. Cumulative live birth rates after IVF in patients with polycystic ovaries: phenotype matters. Reprod Biomed Online 37, 163-171, doi:10.1016/j.rbmo.2018.05.003 (2018).

2 Kalem, M. N., Kalem, Z., Sari, T., Ates, C. & Gurgan, T. Effect of body mass index and age on in vitro fertilization in polycystic ovary syndrome. J Turk Ger Gynecol Assoc 17, 83-90, doi:10.5152/jtgga.2016.15235 (2016).

3 Xu, B. et al. Cumulative live birth rates in more than 3,000 patients with poor ovarian response: a 15-year survey of final in vitro fertilization outcome. Fertil Steril 109, 1051-1059, doi:10.1016/j.fertnstert.2018.02.001 (2018).

4 Luke, B. et al. Cumulative birth rates with linked assisted reproductive technology cycles. N Engl J Med 366, 2483-2491, doi:10.1056/NEJMoa1110238 (2012).

5 Feichtinger, M., Nordenhok, E., Olofsson, J. I., Hadziosmanovic, N. & Rodriguez-Wallberg, K. A. Endometriosis and cumulative live birth rate after fresh and frozen IVF cycles with single embryo transfer in young women: no impact beyond reduced ovarian sensitivity-a case control study. J Assist Reprod Genet 36, 1649-1656, doi:10.1007/s10815-019-01519-5 (2019).

6 Senapati, S., Sammel, M. D., Morse, C. & Barnhart, K. T. Impact of endometriosis on in vitro fertilization outcomes: an evaluation of the Society for Assisted Reproductive Technologies Database. Fertil Steril 106, 164-171 e161, doi:10.1016/j.fertnstert.2016.03.037 (2016).

7 Orazov, M. R., Radzinsky, V. Y., Ivanov, II, Khamoshina, M. B. & Shustova, V. B. Oocyte quality in women with infertility associated endometriosis. Gynecol Endocrinol 35, 24-26, doi:10.1080/09513590.2019.1632088 (2019).

8 Camus, E. et al. Pregnancy rates after in-vitro fertilization in cases of tubal infertility with and without hydrosalpinx: a meta-analysis of published comparative studies. Hum Reprod 14, 1243-1249, doi:10.1093/humrep/14.5.1243 (1999).

9 Kawwass, J. F. et al. Tubal factor infertility and perinatal risk after assisted reproductive technology. Obstet Gynecol 121, 1263-1271, doi:10.1097/AOG.0b013e31829006d9 (2013).

10 Malacova, E., Kemp, A., Hart, R., Jama-Alol, K. & Preen, D. B. Effectiveness of in vitro fertilization in women with previous tubal sterilization. Contraception 91, 240-244, doi:10.1016/j.contraception.2014.12.001 (2015).

11 Wu, J., Yang, X., Huang, J., Kuang, Y. & Wang, Y. Fertility and Neonatal Outcomes of Freeze-All vs. Fresh Embryo Transfer in Women With Advanced Endometriosis. Front Endocrinol (Lausanne) 10, 770, doi:10.3389/fendo.2019.00770 (2019).

12 Ho, V. N. A., Pham, T. D., Le, A. H., Ho, T. M. & Vuong, L. N. Live birth rate after human chorionic gonadotropin priming in vitro maturation in women with polycystic ovary syndrome. J Ovarian Res 11, 70, doi:10.1186/s13048-018-0445-5 (2018).

13 Polat, M., Yarali, I., Boynukalin, K. & Yarali, H. In vitro fertilization for endometriosis-associated infertility. Womens Health (Lond) 11, 633-641, doi:10.2217/whe.15.50 (2015).

14 Briceag, I. et al. Current management of tubal infertility: from hysterosalpingography to ultrasonography and surgery. J Med Life 8, 157-159 (2015).