Increased Oocyte Yield Observed with One-day Delay in Triggering Oocyte Maturation

Rise in the progesterone levels are known to negatively affect pregnancy rates; however, there is lack of sufficient evidence regarding their impact on oocyte yield. A recent randomized controlled trial reports that deferring oocyte maturation trigger by one day, in patients with low levels of progesterone, yielded higher number of mature oocytes. The study findings are published in Reproductive Biology and Endocrinology.

Frank Vandekerckhove, Centre for Reproductive Medicine, University Hospital Ghent, Belgium, and coworkers conducted the study on 262 patients to determine the effect of serum progesterone on the number of metaphase II oocytes. Using ultrasound and hormonal assessment, the patients, who had ≥3 follicles of at least ≥18 mean diameter, were formed into two groups based on serum progesterone levels (>1 ng/mL and ≤ 1ng/mL). It was observed that the patients with ≤1 ng/mL progesterone levels (n=59) had 30%-50% of total follicular count, which were of ≥18 mean diameter. These patients were further randomized into two subsets, wherein oocyte maturation was triggered the same day in one group, while it was done 24 hours later in the other. Similar randomization (regardless of the percentage of large follicles) was conducted on the patients in the other arm who had progesterone concentration of ≥1 ng/mL (n=72).

The results showed that the number of metaphase II oocytes retrieved in the ≤1 ng/mL progesterone group, who received delayed oocyte maturation trigger, was 10.29±6.35 (mean±SD), when compared to the controls (7.64±3.26). The mean difference was found to be 2.41 (95% CI=0.22 to 4.61; P=0.031), following the adjustment for age. In the other study arm (progesterone ≥1 ng/mL), 11.81±9.91 and 12.03±7.09 were the mean number of metaphase II oocytes obtained in the delayed group and controls, respectively. The researchers observed that the mean difference was -0.44 (95% CI= -3.65 to 2.78; P=0.79), after the adjustment for female pathology and polycystic ovary syndrome. Based on the findings, they opined that higher number of oocytes may be retrieved by postponing the oocyte maturation by 24 hours in women with low progesterone concentrations.

In an earlier systematic review and meta-analysis, Venetis et al (Human Reproduction Update, 2013) determined the link between the rise in progesterone levels on the day of hCG administration and the chances of pregnancy in >60,000 fresh, frozen-thawed, and donor/recipient IVF cycles. In fresh cycles, there was a reduced probability of pregnancy in women with elevated progesterone levels (threshold ≥0.8ng/mL) when compared to those who did not have such a rise. However, this adverse impact on pregnancy chances was not observed in frozen-thawed and donor/recipient cycles. The following table indicates the pooled effect sizes:

Table 1: Pregnancy chances in women with different progesterone levels

Progesterone Levels (ng/mL Odds Ratio P value
0.8-1.1 0.79 <0.05
1.2-1.4 0.67 <0.05
1.5-1.75 0.64 <0.05
1.9-3.0 0.68 <0.05


Several studies have demonstrated that endometrial changes may contribute to the negative impact of progesterone on pregnancy outcomes, and hence its effect occurs only in fresh cycles and not oocyte donation programs. In consistent with these findings, two previous trials (Vaerenbergh et al, Reproductive BioMedicine Online, 2011; Bosch et al, Human Reproduction, 2010) noted a change in the gene expression of the endometrium, when the levels of serum progesterone were >1.5ng/mL.

Although the impact of progesterone elevation on the yield of mature oocytes was evaluated in some trials, it was determined only as a secondary variable or not mentioned at all. Moreover, different studies, which were performed earlier, showed variations in the cut-off values for positive levels of progesterone, with no consensus on the conclusions. With the current study focusing mainly on the association between progesterone elevation and mature oocyte yield, the researchers came to the following conclusions:

  • Decision-making on the timing of hCG administration for oocyte maturation is dependent on the progesterone level, once the follicles reach ≥18 mm in diameter
  • Delaying the oocyte maturation trigger by 24 hours will not impact the yield of mature oocytes, if the progesterone level is >1 ng/mL
  • Delaying the oocyte maturation trigger by 24 hours should be considered, only if the level of progesterone is <1 ng/mL and 30-50% of the follicles are ≥18mm.

However, the current study researchers emphasized the need for further larger studies to validate the findings. This was consistent with the opinion of the Brussels GnRH antagonist Consensus Workshop Group (Human Reproduction Update, 2006), which concluded on the need for further exploration before arriving at a consensus on the optimal timing for oocyte maturation.

References

  • Vandekerckhove F, Gerris J, Vansteelandt S, De Baerdemaeker A, Tilleman K, De Sutter P. Delaying the oocyte maturation trigger by one day leads to a higher metaphase II oocyte yield in IVF/ICSI: a randomised controlled trial. Reprod Biol Endocrinol. 2014 Apr 23;12(1):31. [Epub ahead of print]
  • Venetis CA, Kolibianakis EM, Bosdou JK, Tarlatzis BC. Progesterone elevation and probability of pregnancy after IVF: a systematic review and meta-analysis of over 60 000 cycles. Hum Reprod Update. 2013 Sep-Oct;19(5):433-57.
  • Van Vaerenbergh I, Fatemi HM, Blockeel C, et al. Progesterone rise on HCG day in GnRH antagonist/rFSH stimulated cycles affects endometrial gene expression. Reprod Biomed Online. 2011 Mar;22(3):263-71.
  • Bosch E, Labarta E, Crespo J, et al. Circulating progesterone levels and ongoing pregnancy rates in controlled ovarian stimulation cycles for in vitro fertilization: analysis of over 4000 cycles. Hum Reprod. 2010 Aug;25(8):2092-100.
  • Tarlatzis BC, Fauser BC, Kolibianakis EM, Diedrich K, Rombauts L, Devroey P. GnRH antagonists in ovarian stimulation for IVF. Hum Reprod Update. 2006 Jul-Aug;12(4):333-40.

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