Assisted Reproductive Technology in China: A Commentary

Abstract

Over the past few decades, assisted reproductive technology (ART) has rapidly developed in mainland China. The number of ART centers increased dramatically from 85 in 2006 to 375 in 2018. In total, 1.08 million ART cycles were performed in 2018 [1]. Based on the large volume of ART data in China, Chinese researchers have conducted studies on various aspects to improve clinical practice and seek innovations and breakthroughs in the field of ART.

However, the popularity of ART raises concerns regarding the safety of ART offspring [2]. Wang et al. [3] conducted a prospective cohort study to assess the comprehensive health status of school-age children conceived through ART compared to that of children conceived naturally. They found that ART- and naturally conceived children had a similar overall health status, but ART-conceived children had at an increased risk of latent exotropia. Liu et al. [4] performed a matched cohort study to examine the effect of laser-assisted hatching (LAH) on the physical, metabolic, cognitive, and behavioural profiles of singletons conceived through frozen–thawed embryo transfer (FET) at preschool age. The results showed that at 4–6 years of age, the cognitive, metabolic, and physical developmental outcomes of pre-school children born after LAH treatment were comparable to those of pre-school children born without LAH treatment, indicating that LAH is possibly a safe assisted reproductive technology method. This study by Liu et al. is the first follow-up study to assess the health of offspring born after LAH up to the preschool age. Wu et al. [5] investigated the relationship between prolonged ovarian stimulation and neonatal outcomes after autologous fresh embryo transfer (fET) and found that prolonged ovarian stimulation did not increase adverse neonatal outcomes in singleton newborns after autologous fET. This retrospective cohort study by Wu et al. is the first to investigate the effects of prolonged ovarian stimulation on neonatal outcomes after autologous fET. Hu et al. [6] found that the overall risk of perinatal and neonatal complications in singleton live births was higher in patients with poor ovarian response (POR) than in those with normal ovarian response (NOR); however, the risks were similar after logistic regression adjustment. Taken together, these studies indicate that ART does not increase the risk of adverse events in offspring.

Robust evidence of effectiveness and safety is a prerequisite for the introduction of new technologies in reproductive medicine [7]. Chinese researchers are making great efforts to investigate whether each ART intervention improves clinical outcomes. Xu et al. [8] found that higher luteinizing hormone (LH) levels on trigger day were associated with improved pregnancy outcomes in gonadotropin-releasing hormone (GnRH) antagonist protocols. Maintaining an optimal LH range is crucial for balancing oocyte yield and assisting in the success of reproductive technology. Chen et al. [9] conducted a retrospective cohort study to investigate whether serum progesterone (P4) levels on embryo transfer (ET) days correlated with the likelihood of live birth in artificial FET cycles using intramuscular progesterone and found that serum P4 levels on ET days do not predict live birth rate in artificial cycles with intramuscular progesterone. Li et al. [10] performed a retrospective cohort study to investigate the effect of pretreatment with a GnRH agonist (GnRHa) on the clinical outcomes of fresh ETs and FETs in infertile patients with adenomyosis and showed GnRHa pretreatment might be beneficial for LBRs following both fresh ETs and FETs in women with adenomyosis. Sa et al. [11] have shown that ZP gene variants are associated with female infertility, which can potentially affect ART outcomes. Hence, carrier screening is recommended to identify genetic variants in female patients experiencing repeated ART failures.

Recurrent implantation failure (RIF), defined as the failure to conceive after repeated ETs, is often stressful and painful for both patients and doctors, and evidence-based interventions for RIF need more exploration [12]. Li et al. [13] found that comprehensive individualised interventions can substantially improve the clinical outcomes of patients with RIF. Guan et al. [14] performed a secondary analysis of a multicenter, randomised, double-blind, placebo-controlled clinical trial to investigate the benefit of preimplantation genetic testing for aneuploidy (PGT-A) in RIF. They showed that there was no significant difference between the PGT-A and non-PGT-A groups in terms of live birth rate and the incidence of maternal and neonatal complications in patients with RIF aged < 38 years.

Fertility care for patients with cancer is also a topic of great concern [15]. Pan et al. [16] investigated the factors influencing live birth outcomes following in vitro fertilisation (IVF) after conservative therapy in women with early stage endometrioid endometrial cancer (EEC). Endometrial thickness and the number of transferable embryos were found to be crucial factors associated with the success rate of live births in women with EEC undergoing IVF-ET. Lin et al. [17] conducted a mouse model study and revealed that GnRH analogs prevented oocyte loss and damage to embryogenesis in cyclophosphamide mice via the upregulation of AMH and Cox17, respectively.

Moreover, there have been some explorations of disease mechanisms in this special issue. Jiang et al. [18] performed an in vitro cell experiment and found that SigmaR1 forms a SigmaR1/SP3/HDAC complex to inhibit HMGA1 transcription, alleviate ER stress and GC apoptosis, and provide new therapeutic targets for DOR. This study by Jiang et al. is the first to propose that SigmaR1 recruits the SP3/HDAC complex to regulate HMGA1 transcription, contributing to ER stress-mediated ovarian GC apoptosis and providing a new direction for the pathogenesis of DOR. Wang et al. [19] explored the role of endometrial defects in the pathogenesis of abnormal uterine bleeding (AUB). Endometrial defects in caesarean scars contribute more to AUB than myometrial defects. This study by Wang et al. is the first to explore the association between endometrial defects (demonstrated by hysteroscopic and pathological features) in caesarean scar defect and post-caesarean abnormal uterine bleeding symptoms.

In summary, this special issue presents data from Chinese investigators from different perspectives that are critical to reproductive medicine, including offspring safety in ART, strategies to optimise ART outcomes, ART treatment for special patient populations such as patients experiencing RIF and those with malignant tumours, and exploration of the mechanisms of DOR and AUB. All studies were rigorously reviewed to ensure data accuracy and provide meaningful clinical practice guidance. Finally, we are grateful to all the authors, reviewers, and editors for their significant contributions to this special issue in China. These studies provide valuable information for the development of reproductive medicine in China and worldwide.

Yanwen Xu and Yun Sun contributed to guide and summarize the editorial. Fang Gu and Yao Lu contributed to write the maniscript.

The authors declare no conflits of interest.