Tubal re-anastomosis or IVF? A difficult choice to make when seeking reversal

Courtesy: Mayo Clinic 

Surgical re-anastomosis is an effective option, especially for younger women, whereas IVF is more cost effective for older women when seeking reversal of tubal ligation says the results of a systematic review published in current issue of Human Reproduction Update.

Female sterilization is one of the most common method of contraception used worldwide, with nearly 19% of women opting for it. The percentage is higher in Asia and Latin American countries (~ 25%) and lowest in European countries (3.8%).

In the United States, it is second most common method of contraception.  

But, circumstances and relationship change or a personal loss may aspire the women to desire future pregnancies. According to a statistic, up to 14.3% of women request reversal of sterilization. The categorical options are either tubal re-anastomosis or IVF.

Choosing between the two options is difficult decision to make and profoundly affected by many factors like age of women, time elapsed since sterilization, cost and desire for multiple children.

This systematic review looked at factors affecting the success of reversal, compared different methods of tubal re-anastomosis and how these methods fared compared to IVF.

The researchers searched the literature for randomized and non- randomized trials comparing fertility outcomes of various surgical methods and also looked at trails comparing re-anastomosis with IVF.

Women who have earlier suffered from tubal factor infertility were excluded from the analysis.

A total of 37 studies, with 10 689 women was included in the final analysis.  The pooled pregnancy rate after reversal was 42–69%, with variation in rate seen across different methods. About 4-8% of women had ectopic pregnancy after the surgery.

Age of the women at reversal of surgery was the only factor affecting the success rate of the procedure. The way the surgery was done i.e. laparoscopically, robotic and laparotomy using microscope did not play any part in achieving pregnancy.

Rates were lower in macroscopic laparotomic technique, which is currently not in much use.

IVF was better choice for women who were older, but no direct comparison data was available nor any cut-off age limit could be established.

The authors stressed the need of larger, randomized trials in future to compare re-anastomosis vs IVF in terms of  pregnancy rates and cost of procedures.  

News from American Society for Reproductive Medicine (ASRM) 2016 Scientific Congress-- Low AMH levels predict poor outcome in patients undergoing IVF-ET.

Clinical Pearls:

• Patients aged >34 years with low AMH levels displayed poorer IVF-ET outcome particularly, higher miscarriage rates that is not dependent on age and ovarian response to COH.

American Society for Reproductive Medicine (ASRM) 2016 Scientific Congress is currently ongoing (October 15 – 19) at  Salt Lake City, Utah. Some selected abstract and news from the conference.

Anti-Müllerian Hormone (AMH) has long been known to provide insight into ovarian function. It is produced by small, growing follicles, thus providing us with quantitative information on ovarian reserve.

While AMH levels predict the treatment outcome in controlled ovarian hyperstimulation, no data is available on its role in predicting miscarriages in patients undergoing IVF-ET. [1] Researchers are more and more interested to evaluate its role in oocyte competence and embryo health.

Results of a prospective study by  Tarasconi B et al at the ASRM 2016 conference shows the role played by levels of AMH and subsequent miscarriage rate in patients undergoing IVF-ET. [2] The paper is also published in a special supplement of Journal Fertility and Sterility.

The study authors examined 2,365 infertile women undergoing 2,688 IVF-ET cycles. All the women included in the study had serum AMH tested as reference with ELISA. Women were classified into 3 age groups: ≤33 years (n=1,033), 34-36 years (n=690) and ≥37 years (n=965) and into 3 different AMH groups: Low AMH (0.04-1.60 ng/mL; n=540), Intermediate AMH (1.61-5.59 ng/mL; n=1,608), and High AMH (5.60-35.00 ng/mL; n=540).

After analyzing the data by binary logistic regression, it was seen that clinical pregnancy and live birth rate were directly proportional to levels of AMH, with miscarriage rate being highest in the low AMH level group.

The results were statistically significant in older women in the two age groups of 34-36 years and ≥37 years.

When the whole population was included as one variable, regression analysis showed direct association between patient’s AMH levels and rate of miscarriages independent of age and number of oocyte retrieved.

The study findings support the hypothesis that AMH levels are biomarker of oocyte and embryo reproductive health beside predicting number of oocyte obtained by COH. 

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[1]https://www.ncbi.nlm.nih.gov/pubmed/23644117 accessed on October17, 2016.

[2] http://www.fertstert.org/article/S0015-0282(16)61512-1/fulltext

Does intentional endometrial curettage before embryo transfer increases the chances of successful outcome?

Clinical pearls:

• Current research points in favor of performing endometrial scratching between day 7 of previous cycle to day 7 of the embryo transfer cycle resulting in improvement in clinical pregnancy rate and live birth rates in women with more than two previous embryo transfers. 

It is proposed that endometrial scratching or biopsy increases the chances of implantation in women attempting ARTs. With an intention to determine the current practice clinicians across Australia, New Zealand and the UK were given an on-line survey between August to October 2015.  The results of this study was published in the recent issue of Human Reproduction.[1]

In this cross- sectional study spanning 143 private and public fertility centers, 89% of physicians, embryologists and nurses perform the endometrial biopsy or scratching as a part of treatment protocols for couples undergoing IVF.[2]

The most common indication (92%) for the procedure was Recurrent Implantation failure (RIF) while only 3.6% clinicians offered it to patients trying to conceive by natural intercourse or IUI. Although many trials exist documenting the benefit of this procedure in couple trying to conceive naturally. [3]  

It was interesting to see that they all followed different time frame for doing the procedure.

89% of the centers offered the procedure in the luteal phase of the cycle prior to the embryo transfer cycle and none performed it on the day of egg retrieval or embryo-transfer.  

Two- thirds of the responders agreed that it is very useful in RIF undergoing IVF and more than 50% did not think it to be useful before the first IVF cycle.

Currently the most accepted explanation for the success is favorable immune modulation of the endometrium increasing the implantation rate. Other theories are it modulates the gene expression and increases the receptivity. [4]

A review of literature finds many RCTs conducted in the past to gauge the benefit of the procedure.

Results of Cochrane systemic review of 14 Randomized control trial(RCTs) shows that endometrial injury before starting the ovarian stimulation improves the chances of conception and ongoing pregnancy.[5] The evidence is moderate grade and suggests that “Endometrial injury performed between day 7 of the previous cycle and day 7 of the embryo transfer (ET) cycle is associated with an improvement in live birth and clinical pregnancy rates in women with more than two previous embryo transfers.”

With all these evidence pointing in favor of the procedure, a very large and robust study with sufficient power by Yeung et al[6] published in Human Reproduction showed that the procedure does not offer any benefits contrary to the previous beliefs. But, in this study about 70% of the patients received the procedure in their first IVF cycle so the results may not be generalized to patients with RIF.

To conclude, although current evidence is in favor of endometrial scratching, more evidence is needed in the form of large, randomized clinical trials regarding its timing in relation to menstrual cycle, use in women with or without RIF and its use in natural cycles, before this inexpensive and simple procedure can be widely applied in fertility clinics.

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[1] http://humrep.oxfordjournals.org/content/31/6/1241.abstract

[2] http://humrep.oxfordjournals.org/content/31/6/1241.full.pdf+html

[3] Gibreel A, Badawy A, El-Refai W, El-Adawi N. Endometrial scratching to improve pregnancy rate in couples with unexplained subfertility: a randomized controlled trial. J Obstet Gynaecol Res 2013;39:680 – 684.

[4] Zhou L,Li R, Wang R, Huang H-x, Zhong K. Local injury to the endometrium in controlled ovarian hyperstimulation cycles improves implantation rates. Fertil Steril2008;89:1166-1176.

[5] http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD009517.pub3/pdf

[6] http://humrep.oxfordjournals.org/content/29/11/2474.full