Andersen C Yding, Humaidan P, Ejdrup H Bredkjaer, Bungum L, Grøndahl M L, Westergaard L G
Laboratory of Reproductive Biology, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark.
Hum Reprod. 2006 Aug;21(8):2126-30. doi: 10.1093/humrep/del119. Epub 2006 May 8.
A recent prospective randomized study from our group compared GnRH agonist (0.5 mg buserelin) and hCG (10,000 IU) for triggering of ovulation following a flexible antagonist protocol. The agonist group showed a poor reproductive outcome despite luteal phase support with progesterone and estradiol (E(2)). In the present prospective observational study, the health status of follicles from the above study was monitored by analysing the hormonal content of frozen/thawed follicular fluid samples. The aim was to test whether the poor reproductive outcome could be related to a defective pre-ovulatory follicular maturation resulting in oocytes with a compromised developmental competence.
Hormone concentrations were measured in two individual follicular fluid samples from each of 32 women receiving buserelin and 37 receiving hCG, thus representing a subset of the follicles retrieved.
Follicular fluid levels of LH in the agonist group as compared with the hCG group was 11.1 +/- 0.5 versus 3.6 +/- 0.3 IU/l (mean +/- SEM; P < 0.001); FSH, 6.3 +/- 0.6 versus 3.3 +/- 0.2 IU/l (P < 0.001); hCG, not determined versus 139+/-8 IU/l; E(2), 1.9 +/- 0.2 versus 1.8 +/- 0.2 micromol/l (P > 0.10); progesterone, 70 +/- 4 versus 93 +/- 6 micromol/l (P < 0.001); inhibin-A, 36.9 +/- 3.1 versus 37.1 +/- 2.5 ng/ml (P > 0.10) and inhibin-B, 35.6 +/- 2.8 versus 40.1 +/- 3.1 ng/ml (P > 0.10). Thus, pronounced hormonal differences exist in follicular fluid, and the collective concentration of all three gonadotropins and the follicular fluid concentration of progesterone were much higher in the group of women receiving hCG for ovulation induction.
The study suggests that GnRH agonist results in proper pre-ovulatory follicular maturation, but the ovulatory signal--probably in synergy with the resulting pituitary down-regulation--is too low to support appropriate corpus luteum (CL) function.
我们团队最近的一项前瞻性随机研究比较了促性腺激素释放激素激动剂(0.5毫克布舍瑞林)和人绒毛膜促性腺激素(10,000国际单位)在灵活拮抗剂方案后用于触发排卵的效果。尽管使用了孕酮和雌二醇(E₂)进行黄体期支持,但激动剂组的生殖结局较差。在本前瞻性观察研究中,通过分析冷冻/解冻的卵泡液样本中的激素含量来监测上述研究中卵泡的健康状况。目的是测试生殖结局不佳是否可能与排卵前卵泡成熟缺陷有关,从而导致卵母细胞的发育能力受损。
对32名接受布舍瑞林治疗的女性和37名接受人绒毛膜促性腺激素治疗的女性的每个个体的两份卵泡液样本中的激素浓度进行了测量,这些样本代表了回收的卵泡的一个子集。
与hCG组相比,激动剂组卵泡液中的LH水平为11.1±0.5与3.6±0.3国际单位/升(平均值±标准误;P<0.001);FSH为6.3±0.6与3.3±0.2国际单位/升(P<0.001);hCG,未测定与139±8国际单位/升;E₂为1.9±0.2与1.8±0.2微摩尔/升(P>0.10);孕酮为70±4与93±6微摩尔/升(P<0.001);抑制素-A为[36.9±3.1与37.1±2.5纳克/毫升(P>0.10)]以及抑制素-B为35.6±2.8与40.1±3.1纳克/毫升(P>0.10)。因此,卵泡液中存在明显的激素差异,在接受人绒毛膜促性腺激素诱导排卵的女性组中,所有三种促性腺激素的总体浓度以及卵泡液中的孕酮浓度要高得多。
该研究表明,促性腺激素释放激素激动剂可导致排卵前卵泡正常成熟,但排卵信号——可能与由此导致的垂体下调协同作用——过低,无法支持适当的黄体(CL)功能。