How much total ovarian tissue can be removed without compromising ovarian function? An animal study

Abstract

Objective

Removal of ovarian tissue is a new option for fertility preservation for certain cancer patients in China. The aim was to investigate the impact of stepwise removed tissue on hormone levels and follicles in rats.

Methods

Six to ten-week old rats were divided into six groups (% total ovarian tissue): 1 = control (100%), 2 (75%), 3 (50%), 4 (25%), 5 (12.5%), 6 (0%, bilateral ovariectomy). Blood test was carried out fortnightly to assess estradiol (E2), progesterone (P), follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), and inhibin B (INHB). Ovaries are obtained from surgical resections and from rats sacrificed after 12 weeks.

Results

During 12 weeks, groups 4, 5, and 6 had higher FSH and lower AMH and INHB values compared to control (p< .05), but in group 4 E2 and P was not significantly different from control (p> .05). All ovarian function parameters stopped in groups 5 and 6. Follicle morphology was not significantly different between baseline and 12 weeks after surgery in groups 1–5.

Conclusions

For the first time, we demonstrated that even up to 75% of total ovarian tissue can be removed without impact on E2 and P production in rats, which, if confirmed in women, would mean that hazardous (or possibly contraindicated in cancer patients) hormone therapy is not required to avoid the negative consequences of hormone depletion.

摘要

目的：卵巢组织切除冻存是某些癌症患者生育力保护的新选择。本研究目的是研究切除不同体积的卵巢组织对大鼠激素水平和卵泡的影响。

方法：6∼10周龄大鼠分为6组（%=切除不同卵巢体积后剩余的卵巢/全部卵巢组织）：组1, 对照组（100%）、组2（75%）、组3（50%）、组4（25%）、组5（12.5%）、组6（0, 双侧卵巢切除）。术后每两周检测血清雌二醇（E2）、孕酮（P）、卵泡刺激素（FSH）、抗苗勒管激素（AMH）、抑制素B（INHB）。卵巢取自手术切除和术后12周后处死的大鼠。

结果：12周内, 组4、组5、组6 FSH水平明显高于对照组（p<0.05）, AMH和INHB水平明显低于对照组（p<0.05）, 组4 E2和P水平与对照组无显著差异（p>0.05）。组5和组6所有卵巢功能参数均停止。术后12周组1∼5的卵泡形态与基线之间无显著差异。

结论：我们首次证明, 即使切除高达75%的总卵巢体积可以不影响大鼠E2和P的产生, 如果在女性中得到证实, 这将意味着不需要有风险的（或癌症患者可能禁忌的）激素治疗来避免激素缺乏的不良结局。

Keywords:

• Ovariectomy
• ovarian function
• ovarian tissue cryopreservation
• premature ovarian insufficiency
• fertility protection

Acknowledgements

The authors gratefully acknowledge Xingming Li, Associate Professor, PhD, School of Health Administration and Education, Capital Medical University, Beijing, for his support in statistical analysis.

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

This study was supported by Beijing Municipal Administration of Hospitals’ Ascent Plan [DFL20181401]; Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support [XMLX201710]; Medical Health Technology Innovation and Talent Training Special Fund [2017041900004, 2018042000001, 2018042000002]; Beijing Natural Science Foundation (7202047).