NAVILLE, A. H., KISTNER, R. W., WHEATLEY, R. E., & ROCK, J. (1964). Induction of ovulation with clomiphene citrate. Fertility and sterility, 15, 290-309. https://doi.org/10.1016/s0015-0282(16)35225-6
NAVILLE AH, KISTNER RW, WHEATLEY RE, ROCK J. Induction of ovulation with clomiphene citrate. Fertil Steril. 1964;15:290-309. doi:10.1016/s0015-0282(16)35225-6
NAVILLE, A. H., et al. "Induction of ovulation with clomiphene citrate." Fertility and sterility, vol. 15, 1964, pp. 290-309.
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Most women given clomiphene citrate showed signs of ovulation
This 1964 study treated 37 women. Some did not ovulate at all. Others ovulated only sometimes. Doctors at two Boston clinics gave them clomiphene citrate. In 2 out of 3 women without ovulation, signs of ovulation followed clomiphene citrate treatment. Most women with irregular cycles showed signs of ovulation too. Pregnancies followed in both groups.
Key Findings
Among 21 women with no ovulation for at least a year, 14 (66%) showed signs of ovulation, occurring in 29 of 89 treatment cycles (32%).
Among 15 women with irregular ovulation, 14 presumably ovulated, across 49 of 65 treatment cycles.
Three pregnancies occurred among the women with no ovulation, and five occurred among the women with irregular ovulation.
Ovarian cysts developed in 11 patients; 6 had hot flashes, and 4 others reported nausea, blurred vision, or bloating.
One of the pregnancies ended in an early miscarriage. Among three patients inadvertently given the drug in early pregnancy, the authors saw no sign of harm to fetal development.
Interpretation
The source is an early case series with no comparison group. Doctors judged ovulation by three presumptive criteria: temperature charts, tissue samples, and menstrual flow. Urinary hormone tests supported these signs in some women. Some reported ovulations may not have been real. The authors say ovulations in women with irregular cycles might have occurred spontaneously. The 37 women came from two fertility clinics in the early 1960s and may not represent every cause of ovulation problems. The study cannot show that clomiphene caused each pregnancy, and it gives no per-cycle pregnancy rate.
RRM Context
Restorative reproductive medicine looks for why ovulation stops. Causes range from thyroid problems to polycystic ovary changes. The 1964 paper comes before that approach. Its Table 1 sorts each woman without ovulation by type of problem, such as postpartum or hypothalamic, and the treatment is the same drug for all. The paper does show an early use of temperature charting. The tool is still used today to track whether and when ovulation happens.
Our editorial summary of this paper, not the article's abstract.
To compare the impact of expanded polytetrafluoroethylene (PTFE; Gore-Tex Surgical Membrane; W. L. Gore & Associates, Inc., Flagstaff, AZ) and oxidized regenerated cellulose (Interceed TC7, Johnson & Johnson Medical, Inc., Arlington, TX) on the development of postsurgical adhesions. A multicenter, nonblinded, randomized clinical trial. University medical centers. Each barrier was allocated randomly to the left or right sidewall of every patient. Thirty-two women with bilateral pelvic sidewall adhesions undergoing reconstructive surgery and second-look laparoscopy. Adhesion score (on a 0- to 11-point scale), the area of adhesion (cm2), and the likelihood of no adhesions. The use of both barriers was associated with a lower adhesion score and area of adhesion postoperatively. However, those sidewalls covered with PTFE had a significantly lower adhesion score (0.97 +/- 0.30 versus 4.76 +/- 0.61 points, mean +/- SEM) and area of adhesion (0.95 +/- 0.35 versus 3.25 +/- 0.62 cm2). Overall, more sidewalls covered with PTFE had no adhesions (21 versus 7) and, when adhesions were present on the contralateral sidewall, the number of sidewalls covered with PTFE without adhesions was greater than those covered with oxidized regenerated cellulose (16 versus 2). Expanded polytetrafluoroethylene was associated with fewer postsurgical adhesions to the pelvic sidewall than oxidized regenerated cellulose.
Induction of ovulation in the human has been of considerable research interest for several decades. Various hormonal regimens and other procedures have been tried in the past.1 • 2 In spite of all these trials, the problem of ovulatory failure remains a frustrating dilemma for the physician. Recently, the induction of ovulation with clomiphene citrate in about 70% of anovulatory women was reported by our group.3- 6 It was felt that an important breakthrough in this difficult field of endeavor was at hand. 7- 9 Our observations have been confirmed by other groups of investigators.10- 12 The present report embodies a detailed analysis of the results of administration of this agent to 200 women, of whom 179 were anovulatory. The results of our studies on the probable mode of action of this drug are also discussed.
One hundred and thirty-five patients diagnosed as ovulatory failure have been treated in our clinic since 1966. One hundred and eighteen of these have been treated with clomiphene citrate, or more recently, its cisisomer, and 17 patients with long-standing secondary amenorrhea or primary amenorrhea have been treated with human menopausal gonadotropins, in combination with human chorionic gonadotropins. Of the latter group, 14 of the 17 were shown to be capable of response to exogenous gonadotropins and 12 of these ovulated and 7 (50 per cent) became pregnant. The over-all ovulatory rate with clomiphene citrate or its cisisomer was 78 per cent, with a pregnancy rate of 31 per cent. The results of our present investigation with clomiphene citrate in 10 and 20 mg. dosage are presented in detail, and compared with our previous experience with clomiphene. It appears that cisclomiphene 20 mg. is as effective as clomiphene citrate 100 mg., but has the decided advantage of fewer side effects associated with its use. With the human menopausal gonadotrophins, no major complications, such as ovarian overstimulation or multiple pregnancies, were encountered, and we feel this is attributed to careful selection of patients and daily tracking of total urinary estrogens.
PMID 14156906 14156906 DOI 10.1016/s0015-0282(16)35225-6 10.1016/s0015-0282(16)35225-6 Naville et al. 1964, Naville 1964
Cite this article
NAVILLE, A. H., KISTNER, R. W., WHEATLEY, R. E., & ROCK, J. (1964). Induction of ovulation with clomiphene citrate. Fertility and sterility, 15, 290-309. https://doi.org/10.1016/s0015-0282(16)35225-6
NAVILLE AH, KISTNER RW, WHEATLEY RE, ROCK J. Induction of ovulation with clomiphene citrate. Fertil Steril. 1964;15:290-309. doi:10.1016/s0015-0282(16)35225-6
NAVILLE, A. H., et al. "Induction of ovulation with clomiphene citrate." Fertility and sterility, vol. 15, 1964, pp. 290-309.
