In the natural cycle method, hormonal measurements of E2, progesterone (P4), LH, FSH, and anti-Mullerian hormone (AMH), as well as measurement of the number and the size of antral follicles are carried out on the third day of the menstrual cycle (d3), in order to decide whether the cycle is viable for treatment. If it is viable, the level of the four factors, namely, E2, P4, LH, and FSH, and the number and the size of the follicles are measured again on d10. As early as this point, the use of an oocyte maturation trigger may be decided, or oocyte retrieval may be carried out on the spot if the ovulation is about to take place due to the advanced state of the LH surge. If natural ovulation is likely to happen immediately, oocyte maturation is not triggered. The rate of increase in the E2 level per day shows a gradual increase as the follicles grow, normally at 1.2–1.4 times per day. However, this varies depending on the individual, and misreading this rate of increase will result in missing the correct timing for oocyte retrieval. When it is necessary to continue monitoring the follicular growth, the next consultation day must be set based on the E2 level. If advanced LH and FSH surges are observed on the final visit, the state of surge progression is assessed based on the rate of increase of the LH and FSH, obtained by comparing their levels to those of the last visit. The author assesses the progression of the LH surge by categorizing the rate of increase into three levels, namely, less than 1.25 times, 1.25 times or more but less than 3 times, and 3 times or more. The progress of the FSH increase is categorized into two levels, namely, less than 2 times and 2 times or more. The FSH surge normally begins later than the LH surge. Therefore, when the FSH surge is considered to have begun, because its level of increase is twice or more, the LH surge tends to be coming to an end. If the LH surge is still at the beginning stage, it can be arrested by administering 0.25 mg of GnRH antagonist. However, if the LH level exceeds 3 times or more since the last visit, arresting the surge is difficult (Table 6.1).

Oocyte maturation is triggered when the E2 level and the diameter of the dominant follicle, derived by taking the average length of its long and short axis, have reached their optimum conditions. Basically, such optimum conditions would be when the E2 level has reached 264–268 pg/mL, and the follicular diameter has become 16 mm or more, but the E2 level should take priority over the follicular growth. When these optimum conditions are met, oocyte maturation is triggered by administering 300 μg GnRHa by nasal spray. The timing of the oocyte retrieval should be decided according to the progression of the LH surge but should be carried out immediately without applying artificial oocyte maturation if the LH surge has already been completed (Fig. 6.2). In our clinic, every patient’s first oocyte retrieval is carried out by the natural cycle method without exception. There are two requisite conditions for such an indication: the patient has not received any medication in the cycle immediately prior to the treatment cycle, and the treatment cycle is a natural ovulation cycle.

The number of oocyte retrievals in the natural cycle IVF carried out in our clinic for the 2 years from January 1, 2011 to December 31, 2012, was 1979 cases (1979 cycles). The average age of women who underwent the treatment was 37.6 years old (30–45 years old). The level of d3 AMH was 15.6 pM (0.0–108.11 pM), and that of d3 FSH was 8.5 IU/L (1.5–62.3 IU/L). The average number of visits to the clinic was 3.67 ± 0.91 times, and the average number of days from the start of the cycle to the day of the oocyte retrieval was 14.9 ± 2.8 days. The number of cycles where the dominant follicle had ovulated before the day of retrieval was 100 cycles (5.2 %), from which only small follicles were aspirated and retrieved.

The FSH level peaked on d3 and then decreased as the level of E2 increased. It hit the lowest level when the E2 level reached 200 pg/mL on the day before oocyte maturation was triggered but began to rise due to the positive feedback when the E2 level went over 200 pg/mL.

The LH level peaked on d3 and then began to decrease as the level of E2 rose. However, it began to rise due to the positive feedback when the level of E2 went above 150 pg/mL, 2 days before the oocyte maturation was triggered, and increased by 90 % from the day before the oocyte maturation triggering to the day of maturation triggering.

This result shows that the LH surge precedes the FSH surge in the positive feedback.

The increase in rate of the E2 level gradually rose from 6 days before oocyte maturation triggering and showed 35 %, the highest level of increase, 2 days before the maturation triggering to 1 day before the trigger. Therefore, the patient’s next visit to the clinic should be scheduled, based on the increase rate of the E2 level, within 4 days if E2 = 80–100 pg/mL, within 3 days if E2 = 100–120 pg/mL, and within 2 days if E2 = 120–140pg/mL (Fig. 6.2).

The average number of aspirated follicles per patient was 1.13 for dominant follicles developed to a diameter of 11 mm or more and 8.35 for small follicles, the diameters of which were less than 11 mm. The oocyte retrieval rate was 55.6 % and 36.8 %, respectively. The rate of retrieval metaphase II (MII) stage oocytes was 81.0 % and 23.5 %, respectively. The level of maturity was assessed whether the oocyte was denuded immediately after the retrieval or not. All the retrieved oocytes were cultured to blastocysts, and the rate of retrieved oocytes which grew to blastocysts was 38.0 % among oocytes derived from dominant follicles and 6.6 % among oocytes derived from small follicles. The rate of ongoing pregnancies for 22 weeks or longer, including cases where no oocytes were retrieved, was 13.4 %, and 35.7 % of those were achieved from the small follicles (Table 6.2).