Wednesday, December 27, 2017

Stair-step ovulation induction protocols are not just limited to Clomiphene


Stair-step ovulation induction protocol with Letrozole is also as effective as stair-step method using Clomiphene Citrate, and has a slight edge over CC in obese patients reports the result of study published in March issue of Fertility and Sterility.

Stair-step ovulation induction protocols have shown to achieve ovulation induction in shorter time as compared to traditional protocols in women with PCOS. But, so far studies and clinical trials have mainly focused on Clomiphene Citrate(CC).

Letrozole has shown to have superior ovulation rates over CC in women with PCOS, but no study has so far evaluated the stair-step method for Letrozole in cases of absent follicular recruitment after the initial dose.

This Retrospective cohort study recruited 92 infertile PCOS patients, 49 patients completed a letrozole stair-step from Jan 2015-Oct 2016 while 43 patients received stair-step protocols from July 2013-2014.

Letrozole protocol used in the study

CC protocol used in the study 
The demographics of both the groups were nearly similar, except patients in the Letrozole group were obese with a mean BMI of 30.8 as compared to 26.3 in CC group.

Ovulation rates were comparable in both groups (95.9% vs 88.1%, p=0.09), as also time to attain pregnancy, clinical pregnancy rates and side effects.

Thus, letrozole can also be effectively used in stair-step doses for achieving ovulation and pregnancy in PCOS women resistant to traditional protocols.


Tuesday, December 26, 2017

Stair-step clomiphene protocols shortens time to ovulation in women with PCOS

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 Stair-step clomiphene protocol shortens induction time and brings about more ovulation in women with PCOS says the results of a retrospective cohort study published in January issue of Journal Obstetrics and Gynecology.

The researchers looked at traditional and step-up protocol in terms of ovulation rates and time to ovulation in women who have not responded to initial dose of 50mg of clomiphene citrate(CC).

Over a period of 2 years, the study included 109 patients attending a university hospital infertility clinic, with 66 women receiving traditional treatment and 43 were given the stair-step dose of clomiphene.  

The women were monitored for time to ovulation, as well as ovulation rates, clinical pregnancy rates and mild to moderate side effects.

The traditional protocol was used in 2012, in which CC 50mg was given between days 5-9. If no ovulation occurred, the dose was increased by 50mg after a spontaneous menses or a progestin induced bleed.

The stair-step protocol was used in 2013, in which CC 50mg was given between days 5-9. If no developing follicle >10mm was noted between days 11-14, the dose was increased to100mg immediately for 5 days and an ultrasound was repeated 12 days later. The dose was increased in increments of 50mg until a dose of 250mg was achieved.


It was seen that time to ovulation was nearly 50% less with stair-step method as compared with that of traditional method (23±1.8 vs 47.5±12.5 days, p<0.001). With 100 mg of CC, ovulation rates were comparable with both methods but was nearly 3 times with 150 mg CC (37% vs 12%, p=0.004) and 4 times with 200mg CC (21% vs 5%, p=0.01), with stair-step method as compared to traditional one.

Once ovulation was achieved, clinical and overall pregnancy rates did not differ between both the methods (16% vs 17%, p>0.05).

Women with stair-step method did experience mild side effects like headaches, vasomotor flushing, mastalgia and GI more frequently; however, incidence of severe side effects were similar in both the groups.

The authors concluded that stair-step method is an efficient and effective method for ovulation induction with CC at significantly decreased time. Authors of a prospective cohort study even cited the stair-step protocol as an alternative to gonadotrophin therapy with similar efficacy.

The abstract was also presented as 70th Annual Meeting of the American Society for Reproductive Medicine, October 18-22, 2014, Honolulu, Hawaii and could be accessed here.


Monday, December 25, 2017

ACOG updates its guidelines on Nausea and Vomiting in Pregnancy

The American College of Obstetricians and Gynecologists have updated its practice guidelines about managing Nausea and Vomiting in Pregnancy, published in the January issue of Obstetrics & Gynecology.

The guidelines replace the earlier document published in September 2015.

Nausea and vomiting of pregnancy affects nearly 50%-80% of women and ACOG urges obstetrician to start the treatment early before it progresses to hyperemesis gravidarum. "Hyperemesis gravidarum is the most common indication for admission to the hospital during the first part of pregnancy and is second only to preterm labor as the most common reason for hospitalization during pregnancy," they write.

The authors draw attention to the importance of timing of the onset. They explain "The timing of the onset of nausea and vomiting is important — symptoms of nausea and vomiting of pregnancy manifest before 9 weeks of gestation in virtually all affected women. When a patient experiences nausea and vomiting for the first time after 9 weeks of gestation, other conditions should be carefully considered in the differential diagnosis. A history of a chronic condition associated with nausea and vomiting that predates pregnancy should be sought (eg, cholelithiasis or diabetic gastroparesis)."

Level A recommendations (good and consistent scientific evidence):
Treatment should always be started with Vitamin B6 (pyridoxine) alone or in combination with doxylamine as the first line therapy, as it is safe and effective.

Women should be encouraged to start the pregnancy multivitamin 1 month before conception as it is known to decrease the incidence and severity of nausea and vomiting of pregnancy.

ACOG recommends avoiding antithyroid therapy for the transient gestational thyrotoxicosis or hyperemesis gravidarum and urges physicians to only use supportive therapy.

Level B recommendations (limited or inconsistent scientific evidence, include):
Ginger has been found to be effective in some cases of nausea and vomiting and it is recommended as non-pharmacologic therapy.

Methylprednisolone is found effective in some refractory cases of nausea and vomiting of pregnancy, but it should only be used as a last resort, when other treatments have been ineffective.   

Level C recommendations (based on consensus and expert opinion):
Intravenous fluid support should be offered to patients who exhibit sign of dehydration and are unable to tolerate oral fluids.

Dextrose and vitamins should be included in the therapy for prolonged vomiting to correct ketosis and vitamin deficiency, but always administer thiamine before dextrose infusion to prevent Wernicke encephalopathy.

Enteral tube feeding (nasogastric or nasoduodenal) should be started as first line therapy in women with hyperemesis gravidarum who fail to respond to oral medication. Peripheral parenteral nutrition should be used as last resort as it is associated with significant maternal morbidity.

Treating the nausea and vomiting of pregnancy at the very start may prevent it from progressing to hyperemesis gravidarum.

The bulletin also recommends that after the initial workup and hospitalization rules out other comorbidities as cause of vomiting, patient can have the rest of treatment at home too.

Finally, the authors concluded, “Nevertheless, the option of hospitalization for observation and further assessment should be preserved for patients who experience a change in vital signs or a change in mental status, continue to lose weight, and are refractory to treatment."

Abstract
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