目的:IVF是否适用于与年龄相关的不孕症夫妇?
结论:IVF可能对与年龄相关的不孕症具有可疑的效用。
背景:当诊断工作未能确定任何专利原因时,就会诊断出无法解释的不孕症。虽然通常统一管理,无法解释的不孕症可能包括广泛的条件,包括与年龄相关的不孕症(至少在老年女性中)。不幸的是,目前尚无用于鉴定年龄相关性不孕症的有效测试,这些女性通常被视为无法解释的病例.然而,同源ART对这些女性可能不太有效,因为这些技术可能无法治疗衰老对卵母细胞能力的不利影响。
方法:回顾性选择2014年1月至2021年12月接受IVF手术的18-42岁女性。在研究的第一部分,我们的目的是评估不明原因不孕症(即没有明显的不孕症原因)的女性比例是否随年龄增长而增加.在研究的第二部分,不明原因不孕症的女性按年龄1:1匹配,学习期间,和不孕的持续时间,对那些有不孕症专利原因的人来说。如果我们的假设成立,研究的第一部分应强调不明原因不孕症的比例随着年龄的增长而增加。此外,在研究的第二部分,与有明确不孕症原因的女性相比,随着年龄的增长,患者的IVF成功率应急剧下降。
方法:如果妇女尝试怀孕超过2年,他们取回了三个以上的卵母细胞,并且以前没有经历过IVF尝试。我们排除了患有严重男性因素(criptozoospermia)的夫妇,慢性无排卵,未经处理的输卵管积水,或腔内疾病。研究的第一部分旨在调查无法解释的不孕症随年龄的相对比例。第二部分的结果是无法解释的不孕症与解释不孕症之间的活产分布,年龄小于或超过35岁的女性。仅考虑第一个IVF周期的结果(包括新鲜和冷冻周期)。活产率对应于每次取卵一次活产的累积机会。
结果:研究的第一部分选择了一千五百三十五名妇女;其中742名患有无法解释的不孕症(48%)。与年龄≥35岁的女性(52%)相比,年龄<35岁的女性(40%)的诊断频率较低(P<0.001)。考虑到较小的年龄间隔(P<0.001),出现了明显的梯度。总共选择了1134名妇女(567例无法解释的病例和567例解释的病例)进行了研究的第二部分。基线变量在无法解释和解释不孕症的女性之间具有可比性。在35岁以下的女性中(n=229例无法解释的病例和229例解释的病例),在无法解释的不孕症妇女中观察到108例活产(47%),在解释不孕症妇女中观察到88例(38%)。相比之下,在35岁以上的女性中,活产发生在90对(27%)和114对(34%)夫妇中,分别(P=0.03)。患有无法解释的不孕症的老年女性活产的校正比值比(OR)为0.63(95%CI:0.43-0.94)。换句话说,与具有不孕症的专利原因的类似年龄的女性相比,IVF对无法解释的不孕症的老年女性的有效性又降低了37%。此外,当考虑较小的年龄间隔时,在无法解释的不孕症和解释的不孕症之间,年龄对活产的分布产生了一个梯度(P=0.003).总的来说,这些结果支持以下假设:IVF对年龄相关性不孕症女性可能有适度的获益.与解释不孕症的女性相比,不明原因不孕症的女性IVF成功率下降幅度更大,间接提示IVF不能有效治疗年龄相关性不孕症。
结论:我们推测在不明原因的人群中,IVF成功率随年龄的下降幅度更大,可能与年龄相关性不孕症女性比例的增加有关。然而,即使这在理论上是合乎逻辑的,无法使用经过验证的工具来诊断与年龄相关的不孕症,这使得我们的推断具有推测性.我们不能排除其他不明原因的不孕症的患病率也无法通过IVF有效克服,可能会随着年龄的增长而增加。
结论:我们的研究结果表明,IVF对于治疗年龄相关性不孕症可能具有适度的效用。可能会质疑向患有不育症的老年妇女提供此程序。然而,年龄相关性不孕症的诊断仍然具有挑战性,因此确定一种能够可靠诊断年龄相关性不孕症的生物标志物是当务之急.
背景:该研究部分由意大利卫生部资助-目前的研究IRCCS和Ferring支持的特定资助。ES宣布在IBSA和Gedeon-Richter的会议上接受演讲的酬金,他还处理Ferring的私人研究资助,IBSA,Theramex,还有Gedeon-Richter.所有其他作者都没有任何利益冲突要声明。
背景:不适用。
OBJECTIVE: Is IVF indicated for couples with age-related infertility?
CONCLUSIONS: IVF may be of doubtful utility for age-related infertility.
BACKGROUND: A diagnosis of unexplained infertility is drawn when the diagnostic work-up fails to identify any patent cause. Although typically managed uniformly, unexplained infertility is likely to comprise a wide range of conditions, including age-related infertility (at least in older women). Unfortunately, no validated tests for the identification of age-related infertility exist and these women are typically treated as unexplained cases. However, homologous ART may be less effective for these women because these techniques may be unable to treat the detrimental effects of ageing on oocyte competence.
METHODS: Women aged 18-42 years who underwent IVF procedures between January 2014 and December 2021 were selected retrospectively. In the first part of the study, we aimed to assess whether the proportion of women with unexplained infertility (i.e. without patent causes of infertility) increased with age. In the second part of the study, women with unexplained infertility were matched 1:1 by age, study period, and duration of infertility, to those with a patent cause of infertility. If our hypothesis is valid, the first part of the study should highlight an increase in the proportion of unexplained infertility with age. Moreover, in the second part of the study, one should observe a sharper decrease in the rate of IVF success of the procedure with age in women with an unremarkable work-up compared to those with a definite cause of infertility.
METHODS: Women were included if: they had been trying to conceive for more than 2 years, they had retrieved more than three oocytes, and had not undergone previous IVF attempts. We exclude couples with severe male factor (criptozoospermia), chronic anovulation, untreated hydrosalpinx, or intracavitary diseases. The first part of the study aimed at investigating the relative proportion of unexplained infertility with age. The outcome of the second part was the distribution of the live births between unexplained versus explained infertility, in women younger or older than 35 years. Only the results of the first IVF cycle were considered (including both fresh and frozen cycles). The live birth rate corresponded to the cumulative chance of a live birth per oocyte retrieval.
RESULTS: One thousand five hundred and thirty-five women were selected for the first part of the study; 742 of them had unexplained infertility (48%). The frequency of this diagnosis was lower among women aged <35 years (40%) compared to those ≥35 years (52%) (P < 0.001). A clear gradient emerged when considering smaller intervals of age (P < 0.001). A total of 1134 women (567 unexplained cases and 567 explained cases) were selected for the second part of the study. Baseline variables were comparable between women with unexplained and explained infertility. Among women younger than 35 years (n = 229 unexplained cases and 229 explained cases), 108 live births were observed in women with unexplained infertility (47%) and 88 in those with explained infertility (38%). In comparison, among women older than 35 years, the live births occurred in 90 (27%) and 114 (34%) couples, respectively (P = 0.03). The adjusted odds ratio (OR) for a live birth in older women with unexplained infertility was 0.63 (95% CI: 0.43-0.94). In other words, the effectiveness of IVF in older women with unexplained infertility is reduced by an additional 37% when compared to women of similar age with a patent cause of infertility. Moreover, when considering smaller intervals of age, a gradient of the adverse effect of age on the distribution of live births between unexplained and explained infertility emerged (P = 0.003). Overall, these results support the hypothesis that IVF may be of modest benefit in women with age-related infertility. The decline in IVF success is sharper in women with unexplained infertility compared to those with explained infertility, indirectly suggesting that IVF cannot effectively treat age-related infertility.
CONCLUSIONS: We postulated that the greater decline in IVF success with age in the unexplained group could be related to the concomitant increase in the proportion of women with age-related infertility. However, even if this is theoretically logical, the unavailability of validated tools to diagnose age-related infertility makes our inference speculative. We cannot exclude that the prevalence of other unknown causes of infertility that cannot also be effectively overcome with IVF could increase with age.
CONCLUSIONS: Our findings suggest that IVF may be of modest utility for treating age-related infertility. Offering this procedure to older women with an unremarkable infertility work-up may be questioned. However, the diagnosis of age-related infertility remains challenging and identifying a biomarker that could reliably diagnose age-related infertility is a priority.
BACKGROUND: The study was partially funded by the Italian Ministry of Health-current research IRCCS and by a specific grant supported by Ferring. ES declares receiving honoraria for lectures at meetings from IBSA and Gedeon-Richter and he also handles private grants of research from Ferring, IBSA, Theramex, and Gedeon-Richter. All the other authors do not have any conflict of interest to declare.
BACKGROUND: N/A.