Infertility in women - Emerging treatments

Oocyte cryopreservation

The egg is the largest cell in the body and contains a large amount of water, rendering it more difficult to freeze and thaw compared with an embryo. The process must be completed without the formation of ice crystals which can destroy the meiotic spindles. Advances with slow-freeze techniques and vitrification (rapid cooling) have improved the success and now many children have been born from frozen oocytes worldwide. Improvements in this technique will enable women to preserve their fertility by banking oocytes. It will also improve the ability to efficiently use donor eggs by establishing cryopreserved oocyte banks. Since 2013, the American Society for Reproductive Medicine has considered success rates and safety data are such that oocyte vitrification should no longer be considered experimental.[179] Randomized controlled trials of fresh versus frozen thawed oocytes indicate similar implantation and clinical pregnancy rates.[180] Age at egg harvest and the number of mature oocytes cryopreserved are directly associated with expectant success rates.[181]

Preimplantation genetic testing for aneuploidies (PGT-A) during routine IVF

Despite transferring healthy-appearing embryos, implantation rates remain approximately 40% (for women younger than age 35) after IVF.[177] Several investigators have sought to improve these rates by biopsying the embryos to assure that they are not aneuploid. Significant technological advances have been made in this sector of reproductive medicine, whereby preimplantation genetic testing for aneuploidies (PGT-A) is largely performed on blastocysts using Next Generations Sequencing (NGS). The technique allows detection of aneuploidy, polyploidy, unbalanced translocation, segmental aneuploidy and mosaicism to name a few. However, despite advances made, routine PGT-A has not been shown in large multicentered randomized controlled trials to increase the ongoing pregnancy rate per embryo transfer and is not recommended.[2][182][183]

Uterine transplantation

The first successful live birth after uterine transplant in 2014 heralded the potential for women with severe anatomical uterine problems (e.g., congenital absence of the womb) to carry a pregnancy. Requiring the administration of anti-rejection drugs and advanced planning, with the involvement of highly skilled transplant surgeons, this is not an easy option and is offered by only a few subspecialist centers worldwide. Although hopeful, at present it remains an experimental procedure for the treatment for uterine factor infertility.[184][185]

Platelet-rich plasma injection

In women with diminished ovarian reserve, treating the ovaries with platelet-rich plasma may restore ovarian activity and enhance follicular growth.[186] Meta-analyses suggest that autologous platelet-rich plasma injection improves ovarian reserve markers and significantly increases the number of oocytes and embryos created with assisted reproductive technology (ART) among women with diminished ovarian reserve or poor response to ovarian stimulation.[186][187] In an analysis of patients with poor reproductive prognosis (whose only option is typically to use donor oocytes), the spontaneous pregnancy rate was 7% and the live birth rate with ART was 11%.[186]

Growth hormone supplementation

Poor ovarian response occurs in around 5% to 18% of ART cycles and is associated with significantly reduced pregnancy rates.[188] Growth hormone supplementation may improve ART success rates in women with poor ovarian response or diminished ovarian reserve by regulating ovarian function, promoting follicular maturation, and enhancing endometrial receptivity.[188][189] Meta-analyses suggest that growth hormone supplementation improves live birth rate while reducing the cycle cancellation rate and the total dose of gonadotropins required for ovarian stimulation.[188][189][190] However, the risk of bias and heterogeneity in the included trials was high.

Unconventional ART protocols

Conventional ART protocols start ovulation stimulation in the early follicular phase. One meta-analysis found that luteal phase stimulation may result in a similar number of retrieved oocytes and double stimulation may result in a higher number of retrieved oocytes and more euploid embryos.[191] However, data on live birth and miscarriages rates were limited, and most included studies were observational and at high risk of bias.[191]

Progestin-primed ovarian stimulation

In one meta-analysis, progestin-primed ovarian stimulation was equally effective in terms of clinical pregnancy rate and live birth rate compared with conventional ovarian stimulation protocols (gonadotropin-releasing hormone analog).[192] Progestin-primed ovulation stimulation has the advantage of oral administration and low cost, but it is not routinely recommended due to limited evidence.[192][193]

Herbal medicines

Herbal medicines have been suggested as an alternative or complement to conventional fertility treatment, but the mechanisms are not well understood.[194] In one systematic review, herbal medicine treatment significantly improved pregnancy rates compared with placebo, but the quality of the included studies was low.[195]