Dear Colleagues

At the outset : I wish you a very happy and prosperous new year. We are entering into seventh year of publishing this news letter.

As things are progressing ,we started a small academic club in Jabalpur

In this club very young gynecologists are given chance to put their views in different topics on the field of ObGy and reproductive medicine. We also started fortnight journal review club also. We welcome you all.

In this month ,two topics I came across ,which I feel will be interesting for you too.

When a woman with Polycystic ovarian disease  is taken for ovarian stimulation either for IUI or IVF , we all notice that either they over-respond or donot respond. What should be actual way of stimulation is still a matter of debate. I try to put some views collected from various literatures to make the things little clear.

Another topic is very simple ,that is distension media in hysteroscopy and its complications. The complications are rare but can take place if we are not vigilant enough regarding the in-flow and out-flow during hysteroscopy.

I welcome your comments to improve the quality of this News letter and request you to contribute in this. There are various good practical ideas practiced by our various colleagues ,those can be shared by this medium. I will be a great booster for me.

With warm regards

Dr.D’Pankar Banerji

1.Stimulating polycystic ovaries for IVF

In IVF we need multifollicular development, resulting in the collection of several appropriately mature eggs, but without causing Ovarian Hyper stimulation syndrome

(OHSS). OHHS is one of the main problems in stimulating the PCOS. These females have ovaries those more sensitive than the normal ovaries to the exogenous stimulation.

It was earlier believed that, more the eggs collected more are the chances of pregnancy, but contrary to this it is seen that collection of large number of oocytes (more than 10) results in a poor outcome, the optimum number being between seven and nine. This is of particular relevance to women with polycystic ovaries in whom there are often a high number of oocytes, yet poor rates of fertilization and implantation and a higher miscarriage rates.

There are following methods for stimulation

1. Clomiphene citrate and HMG
2. FSH and HMG
3. GnRh analogues and FSH/HMG
4. GnRh antagonists

With clomiphene citrate and HMG there is a chance of premature LH surge results in abnormal maturation of the oocytes and even rupture of follicle before collection of the oocytes. This problem is more often seen in-group of patients of PCOS, hence not much in use.

There are few studies that have specifically compared different treatment regimens for women with and without polycystic ovaries. The two particular aims pf therapy in this group of women are the correction of the abnormal hormone milieu, by suppressing elevated LH and androgens, and the avoidance of ovarian hyperstimulation. Pituitary desenstization avoids the initial surge of gonadotropins with the resultant ovarian steroid release that occurs in the short GnRh protocol. Although the long protocol theoretically provides controlled stimulation, the polycystic ovary is still more likely than the normal ovary to become hyper stimulated. With both long and short protocols, significantly more eggs are collected from women with polycystic than normal ovaries and interestingly total dose of exogenous gonadotropins is the same for either regimen. It has also suggested that longer period of desensitization (30 instead of 15 days) is of benefit by reducing androgen levels

Debates in PCOS:

• Whether use of FSH alone or HMG, as LH levels are comparatively higher in circulation.
•  Whether hyper secretion of LH is responsible for exaggerated response to stimulation of the polycystic ovary?
• Does minimizing circulating LH levels by giving FSH alone improve outcome? 

Most studies have found no benefit over hMG from the use of FSH alone in ovulation induction. The most probable reason is that there are only 75 units of LH activity in each ampoule and when hMG is given in standard doses to patients who are receiving treatment with buserelin, the serum LH levels barely rise to above 5 IU/L. In patients with PCOS the serum LH concentration is usually 2-4 times that levels – that is, the serum levels represents a higher “secretion rate” than that mimicked by injections of hMG.

Few studies show the following trends:

1. In long protocol regime use of urinary FSH and hMG shows no difference in outcome.
2. Recombinant FSH gives higher number of oocytes and a shorter duration of treatment in clomiphene resistant anovulatory patients
3. Low dose stimulation protocol with rFSH can lead to higher pregnancy rate in IVF patients with PCOS. It has less chances of Ovarian Hyperstimulation syndrome
4. Ovarian stimulation after suppression with GnRh analogue: study between urinary FSH and rFSH shows that rFSH is more effective, less requirement and higher pregnancy rate, although the observed magnitude is less. (Cochrane Database of Systematic reviews, 2001) 

Gonadotropin releasing hormone antagonists (GnRh antagonists) are the new entry in the felid of ovarian stimulation. These molecules do not activate GnRh receptors but they instantly block them and gonadotropin secretion is suppressed in hours. The new IVF protocol using GnRh antagonists can offer a shorter and simpler protocol. A systematic review in the Cochrane Database showed that there is a trend of reduction of ovarian hyperstimulation syndrome in GnRh antagonist treatment group.

Another advantage of using GnRh antagonist is that the native GnRh or GnRh agonist can displace the antagonist from the GnRh receptors at the pituitary level. Therefore, in GnRh antagonist IVF cycle, GnRh agonist can be administered to induce in LH surge and to trigger the final oocyte maturation and ovulation. Number of oocytes and their maturation were comparable to HCG triggering ovulation. GnRh triggering is more physiological and can reduce the risk of OHSS due to a short half life (60 min vs. 32-34 hrs.).

2.Complications caused by hysteroscopic distension media

High viscosity (eg, Dextran 70), low-viscosity/electrolyte poor (eg. Glycine and sorbitol), and low viscosity electrolyte containing (eg, normal saline and lactated Ringer’s solution) medias are commonly used for distension of the uterus during hysteroscopy. The use and safely profiles of these medias vary, however.

Dextran 70 is used because of its excellent visibility, but the manufacturer recommends that no more than 250 ml is absorbed because of the concern for pulmonary edema. Anaphylactic reactions and coagulopathy also are rare complications that have been described.

Glycine and sorbitol allow the use of monopolar cautery during operative hysteroscopy. Large volume deficits have been associated withy hyponatremic hypervolemia however. After intravasation , glycine and sorbitol are metabolized , leaving free water. This free water accumulates I the brain and increases intracranial pressure. When fluid deficits reach 1000 to 1500 ml. The procedure should be terminated and the patient’s serum electrolytes should be assessed. Patients who have excessive intravasation experience headache, nausea, vomiting and agitation. This manifestation can progress to pulmonary and cerebral edema. These patients require close monitoring and diuretic administration.

Unlike glycine and sorbitol, normal saline and lactated Ringer’s solution have physiologic osmolarity and contain sodium. Although excessive intravasation does not lead to hyponatremia, it can lead to volume overload. Media deficits of greater than 2500 ml should prompt conclusion of the procedure, and the patient’s electrolytes should be assessed.

Several fluid-management systems are available to monitor closely the amount of distension media lost during hysteroscopy, and by minimizing operating time. The physician must be aware that certain procedures such as endometrial ablation and resection of myomas open vascular channels and place the patient at increased risk for fluid overload.

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