| Drug: | Clomid / Clomiphene |
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Two years ago, the results of treatment with Clomid in 2,616 anovulatory patients were presented to the Pacific Coast Fertility Society. That data came from a large pool of individual clinical records collected during early studies with Clomid.
Since then, records from over 4,000 additional patients have been added and analyzed using an updated diagnostic system. This report shares new insights based on that expanded dataset and looks at how certain usage patterns have become clearer over time.
Pregnancy Outcomes
Table 1 summarizes the outcomes of 2,196 pregnancies that occurred during clinical research involving Clomid (data collected up to June 28, 1967). Because this report includes all investigational use of Clomid, some patients received the drug for reasons other than ovulation issues.
At the time of reporting, 1,744 pregnancies had resulted in delivery. Another 452 were either still ongoing or lacked follow-up data. For clarity, miscarriages, stillbirths, and ectopic pregnancies were grouped together. Among those 407 cases, there were 2 therapeutic abortions, 2 iatrogenic abortions, 4 molar pregnancies, 1 fetus papyraceous, and 24 ectopic pregnancies.
There were 1,201 single live births, with 1,179 infants surviving the perinatal period. Notably, when conception occurred during a Clomid cycle, the rate of multiple pregnancies increased nearly tenfold. In total, 305 infants were born from 136 multiple pregnancies. Of these, 251 survived the perinatal period, including 27 out of 58 babies from triplet, quadruplet, and quintuplet births.
Among the 1,744 completed pregnancies associated with Clomid, 38 birth defects were reported. Five infants were diagnosed with Down syndrome, while the rest included a wide range of anomalies familiar to obstetricians. At this point, there is no clear evidence linking Clomid to birth defects in humans, and no consistent pattern of abnormalities has been observed. However, the drug remains strictly contraindicated during pregnancy.
Ovulatory Response to Clomid
The latest data includes 4,098 anovulatory patients who were either newly added or reanalyzed since the previous report. As shown in Figure 1, ovulatory dysfunction is a complex issue, and strict diagnostic categories are often difficult to apply. The classifications used here represent the best effort to group patients based on the clinical and lab data submitted by researchers.
Ovulation was confirmed using various indicators such as basal body temperature (BBT) charts, endometrial biopsies, pregnanediol levels, and other clinical signs. Since the start of clinical trials, the overall ovulatory response to Clomid has held steady at around 70%.
Interestingly, although ovulation rates have stayed constant, the pregnancy rate has slightly improved over time—reaching 31% in this analysis. This might suggest that doctors have gotten better at identifying which patients are most likely to benefit. Still, the gap between ovulation and actual pregnancy remains a puzzle and deserves further research.
Conditions That Respond Best to Clomid
The strongest ovulatory response to Clomid was seen in women with:
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Polycystic ovary syndrome (PCOS)
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Post-contraceptive amenorrhea
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Oligo-ovulation (cycles every 1–6 months)
In these cases, ovulation occurred in 75–80% of patients, and about 35% went on to become pregnant.
On the other end, Clomid was far less effective for women with pituitary dysfunction or ovarian insufficiency—there were virtually no pregnancies in these groups. This reinforces the idea that a functioning pituitary-ovarian axis is essential for Clomid to work.
For patients with other conditions, the response varied:
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41.6% ovulated in cases of lactation-related amenorrhea
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59.9% in psychogenic amenorrhea
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If amenorrhea lasted more than 6 months, response dropped to 53%, with a matching decline in pregnancies
The category “Other Indications” included rarer disorders like adrenal hyperplasia, postpartum amenorrhea (without lactation), and several unclassified hormonal conditions.
Role of Endogenous Estrogen
Roughly two years ago, researchers began recording each patient’s estrogen status as part of the treatment assessment. Estrogen levels were categorized as good, poor, absent, or variable—based on tests like vaginal smears, withdrawal bleeding after progesterone, cervical mucus quality, endometrial biopsies, or estrogen blood tests.
As seen in Table 2, the response to Clomid strongly depended on the patient’s estrogen profile. Women with fluctuating estrogen (anovulatory cycles) often responded well to treatment—although the sample size was limited.
In general, estrogen status was a good predictor of how well a patient might respond to Clomid, but not reliable enough to rule someone out entirely. For example, even among patients with PCOS and low or absent estrogen, around 70% still responded to Clomid.
Comparing Dosage Schedules
Table 3 compares the two most common Clomid dosage regimens:
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50 mg per day for 5 days (usually on cycle days 5–9)
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100 mg per day for 5 days, same timing
Surprisingly, the ovulation and pregnancy rates were nearly identical between the two approaches. That’s why doctors usually start with 50 mg, and only increase to 100 mg if there’s no response.
Lower than 50 mg per day significantly reduced the effectiveness of the treatment, while doses above 100 mg didn’t seem to offer any additional benefit and could increase the risk of side effects.
Conception Rates and the Husband’s Fertility Status
Sometimes, drug labeling can sound vague or arbitrary when taken out of context. A good example is the FDA’s official indication for Clomid, which reads:
“Clomid (clomiphene citrate) is indicated for the treatment of ovulatory failure in patients desiring pregnancy, and whose husbands have adequate sperm.“
But what exactly does “adequate sperm” mean? The label doesn’t define it. In practice, it refers to sperm that are likely sufficient for fertility. Unfortunately, there’s no universal agreement on what makes a man “fertile” — in terms of sperm count, shape, and motility — so the interpretation varies.
That’s why it’s interesting to look at real-world data showing how the husband’s fertility status affects conception in women treated with Clomid.
How the Husband’s Fertility Affects Conception
Table 4 breaks down the conception rates based on how the husband was classified — fertile, subfertile, or infertile — by the treating physician or urologist. There were no strict standards used for these labels, but the trends are clear.
Women whose husbands were considered fertile had the highest conception rates. In the subfertile group, conception still occurred in a meaningful number of cases — showing that “subfertile” doesn’t mean “hopeless.” It just means the sperm may not be ideal, but still adequate for potential fertility.
In contrast, the conception rate among those with infertile partners was just 4.3%, which is expectedly low and statistically weak.
Side Effects of Clomid Therapy
Since clinical trials began, more than 6,700 anovulatory patients have been treated with Clomid, and their experiences reveal a lot about side effects. These are outlined in Figure 2 and generally correlate with dose level — earlier studies often used higher or prolonged dosing compared to today’s standards.
At recommended doses, ovarian enlargement was uncommon, although normal cyclical changes in ovary size could be exaggerated. Some patients experienced sharper mid-cycle pain (mittelschmerz) as well.
Higher or extended dosing sometimes led to:
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Ovarian cysts
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Enlarged ovaries
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Prolonged luteal phases
In rare cases, women developed severe ovarian enlargement, requiring laparotomy. However, today’s consensus is that most of those situations could have been handled non-surgically.
| 60 pills | $0.58 | $34.63 | ||
| 90 pills | $0.52 | $4.99 | $51.94 $46.95 | |
| 120 pills | $0.49 | $9.97 | $69.25 $59.28 |
Visual and Other Reactions to Clomid
Some women reported visual disturbances like blurriness, flashing lights, or spots. These symptoms usually faded within days or weeks after stopping Clomid, and were thought to be caused by prolonged afterimages.
Hot flashes similar to those during menopause were sometimes noted, but usually mild and short-lived. Abdominal discomfort was most often tied to ovulation or premenstrual symptoms.
Nausea and occasional vomiting were also reported, but less frequently. Other minor complaints were logged too, but most weren’t serious enough to limit treatment.
We Still Don’t Fully Understand How Clomid Works
Despite all the data collected — and even with computers — the exact mechanism of action behind Clomid is still not fully understood. It’s believed that the drug increases the release of pituitary gonadotropins, which helps trigger ovulation.
But how that stimulation works at the molecular level remains a mystery.
Chances are, the answer won’t come from algorithms, but from careful observation by smart, experienced clinicians — the ones who notice patterns machines can’t see.