ASRM guidelines update: Metformin alone is not the first line of treatment for ovulation induction in women with PCOS

Practice Committee of the American Society for Reproductive Medicine does not recommend Metformin alone for ovulation induction as a first line therapy in women with PCOS. The guidelines were published in Journal Fertility and Sterility Epub ahead of print.

Metformin is a biguanide used as an oral insulin lowering agent in type2 diabetes, but also used enthusiastically in women with PCOS because of shared pathophysiology of insulin resistance in both.

A review of clinical data has however failed to support its use as first-line therapy in PCOS and for treating hirsutism.

A review of RCTs showed that metformin alone only increases the ovulation rate but letrozole and clomiphene citrate alone are more effective in terms of ovulation, pregnancy and live-birth rates.

When Metformin alone was compared with Clomiphene alone, evidence suggested that it is less effective for ovulation and live-birth rates.

Metformin is recommended as a second line therapy in combination with gonadotrophins for clomiphene citrate resistant and/or obese PCOS patients. However, there is good evidence that live pregnancy rate remains the same with this combination.

Metformin can only be used as first line therapy if facilities are not available to monitor the more effective therapies of clomiphene citrate and letrozole.

A 2016 analysis of evidence to help WHO formulate global treatment guidelines for the management of anovulatory infertility in women with polycystic ovary syndrome (PCOS) also does not recommend metformin alone as first-line therapy. Its use is recommended as an adjunct to GnRH-agonist long protocol IVF or ICSI treatment to reduce the risk of ovarian hyperstimulation syndrome.

Metformin should be stopped as soon as pregnancy is achieved because it does not help in reducing routine pregnancy complications. The Endocrine Society and NICE Guidelines on PCOS state that the routine use of metformin during pregnancy in women with PCOS is unwarranted, although it may be useful to treat gestational diabetes, and therefore recommended against the use of metformin for the prevention of pregnancy complications.

Abstract

ASRM's guidelines for the limits on the number of embryos transferred in In Vitro Fertilization (IVF) cycles.

courtesy: https://sickbayby.wordpress.com/tag/multiple-gestation/

In order to promote singleton pregnancies and bring down the number of multiple pregnancies in patients undergoing IVF, American Society for Reproductive Medicine (ASRM) and Society for Assisted Reproductive Technology (SART) updated the guidelines regarding the upper limit number of embryos transferred in IVF cycle. These guidelines replace the previous guidance issued in 2013.

The guidelines were  published online in the forthcoming issue of Journal of Fertility and Sterility.

The incidence of triplets and higher order multiple births have essentially declined in US for the last 15 years after steadily rising fourfold during the 1980s and 1990s. But, still multiple births are not desirable outcome of ART therapy.

The rise was due to older maternal age and increased use of ARTs, with no guidelines on the number of embryos transferred.

                                                     

Triplets

Triplets and Higher order births continue to have poor prognosis with 7% succumbing in first year of life as compared to .5% of singleton pregnancies. The ideal outcome after an ART procedure is to have a singleton pregnancy.

National data from CDC in 2013 demonstrate that clinics that perform higher rates of elective single-embryo transfer (eSET) in women aged <38 years have decreased rates of multiple gestation, with no significant impact on cumulative live-birth rates.

In women who are 42 years or younger transferring a single euploid blastocyst resulted in pregnancy rates similar to transferring two untested blastocysts while dramatically reducing the risk of twins.

Patient has the choice to choose the number of embryos transferred but it should be a fully informed decision taking into consideration medical, ethical and financial aspects of the procedure.

For drafting the recommendations, the patients have been categorized into favorable prognosis group and all others.

Conditions associated with favorable outcome are young age: euploid embryos, one or more good quality embryo available for cryopreservation and previous history of livebirth after an ART cycle.

For frozen embryo transfer the favorable conditions are when high quality, vitrified, day 5 or 6 blastocysts available.

The number of embryo transferred should be agreed upon by the treating physician and patients, depending upon the patient characteristics, data for the individual procedure and data from the ART services provided by the clinic. The following guidelines recommend the upper limits of the number of embryo transferred.

Patient with favorable prognosis:

A single euploid embryo transferred in patient of any age has the most favorable prognosis.

Patients under the age of 35 are always encouraged to receive one single embryo, irrespective of the embryo stage.  

Similarly, for patients between 35-37 years of age, a single embryo transfer is encouraged.

Patient between 38-40years of age, a single euploid embryo should be transferred, if availability is restricted than three cleavage-stage embryos or two blastocysts should be transferred.

Similarly, for patients between 41-42 years of age, the choice is to transfer single euploid embryo, if not than four cleavage-stage embryos or three blastocysts is the second choice.

Other scenarios:

In each of the above age group, if the patients do not belong to favorable prognosis category they can receive an additional embryo based on individual circumstances.

If patients who are in favorable prognosis category but fail to conceive after repeated cycles than an additional embryo may be transferred. If these patients have some coexisting medical condition that put them at high risk because of multiple gestation, a single embryo transfer is recommended.

In cases where the number of blastocysts transfer exceed the recommended limit, patient should receive counselling and everything should be well documented on the medical record.

Patients who are more than 43 years of age, insufficient data exist for number of embryos to be transferred using her own oocytes. The risk of multiple pregnancy increases dramatically as age increases, so caution must be exercised.

In donor-oocyte cycles decision should be made according to donor's age.

In frozen embryo transfer cycles, the patient should be categorized into favorable/other scenarios  group according to age of women when the embryo was frozen. And the number of frozen embryo transferred should not exceed the number of fresh embryo transfer recommended for each age group.

The full article in the Journal of Fertility and Sterility can be accessed here.