Clomiphene compared with other drugs in terms of ovulation, EMT, pregnancy and live births: systematic review and meta-analysis

Ovulation induction with Clomiphene Citrate (CC) in women with WHO group II ovulatory disorders results in lower endometrial thickness (EMT) as compared to other regimens. The regimen also resulted in lower number of pregnancies and live births reports the results of systematic review and meta-analysis published in Journal Ultrasound in Obstetrics and Gynecology.

WHO group II ovulation disorders are defined as dysfunctions of the hypothalamic-pituitary-ovarian axis. This category includes conditions such as polycystic ovary syndrome (PCOS) and hyperprolactinaemic amenorrhoea. Around 85% of women with ovulation disorders have a group II ovulation disorder.

This systematic review and meta-analysis only focused on randomized control trials(RCTs) and included all those studies comparing CC with any other regimens and looked at EMT and rates of ovulation, pregnancy and live births.

The other regimens included in the study were Letrozole, CC plus metformin, CC plus N-acetyl cysteine (NAC), CC + nitric oxide (NO) donor and Tamoxifen.

The researchers selected 33 RCTs from 1718 articles that fitted the inclusion criteria amounting a total of 4349 women and 7210 ovulation induction cycle.

Maximum number (15) of RCTs compared CC with Letrozole. Overall the mean EMT was 1.39mm lower in CC group as compared to Letrozole. (WMD, −1.39; 95% CI, −2.27 to −0.51; I² = 100%), and women on CC had a 22% lower chance of pregnancy and 30% lower chance of live births. The ovulation rates were comparable between the two groups.

Only 2 RCTS were found comparing CC with CC plus metformin and no significant difference were noted in any of the outcome parameters between the groups.

When comparing CC with CC plus N-acetyl cysteine (NAC) and CC plus nitric oxide (NO) donor, EMT was lower in CC only group, along with ovulation and pregnancy rates.

When the CC regimen was compared with Tamoxifen, lower EMT and comparable ovulation and pregnancy rates were noted.

The authors concluded that in women with WHO group II ovulatory disorders, Letrozole seems to benefit these women more in terms of increased EMT, ovulation, pregnancy rates and live births. 

Whether the increase pregnancy rates and live births rates are due to increase in EMT has not been looked at in this study.

Abstract

Revolutionary technique prints pure medications on any surface, in combination to accelerate drug delivery and new drug development.

Condensed drug films

University of Michigan have developed a way to print pure medication, without any solvent, in various combination which could one day result into pharmacies printing drugs to fill prescription onsite, as per individual requirement.

The technique was developed at University of Michigan and the research paper published September 27, 2017 in Journal of Nature Communications.

There is a huge unmet need of developing, alternative drug delivery systems that are precise, quick and deliver the drugs directly to the site. In this paper, the researchers make use of solvent-free organic vapor jet printing to deposit micronized and nano-structured thin film of drugs on skin and buccal patches or ingestible strips or any other structure.

This technique improves the dissolution kinetics of active pharmaceutical ingredients (APIs),which increases the efficacy and bioavailability. The new method uses organic vapor jet printing (OVJP), in which the compound is thermally evaporated to mix with inert gas ( Nitrogen) followed by condensing the gas mixture onto cooled substrate, where the organic material condenses.

The process is controlled so that the shape, thickness and morphology of resulting film can be regulated.

The process does not change the chemical properties or stability of the drug. They have experimented with 6 common drugs caffeine, paracetamol, ibuprofen, tamoxifen, BAY 11-7082 and fluorescein.

It was shown that the pure, printed tamoxifen destroyed cultured breast and ovarian cancer cells in vitro as effectively as medication delivered by traditional means. The advantage was the new system did not use any solvent or other compounds that pharma company use to lend stability to the drug.

 Max Shtein, professor of materials science and engineering said, “A doctor or pharmacist can choose any number of medications, which the machine would combine into a single dose. The machine could be sitting in the back of the pharmacy or even in a clinic.”

"Pharma companies have libraries of millions of compounds to evaluate, and one of the first tests is solubility," Shtein said. "About half of new compounds fail this test and are ruled out. Organic vapor jet printing could make some of them more soluble, putting them back into the pipeline."

While printing drugs for mass market might be years away, the immediate use of this technique can be in drug testing, drug developing and evaluating the drugs for human use.

Full text of the paper

NewsletterUniversity of Michigan

Watch a video about the technique