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Newsletter No. 17
  1. PCOS and ovarian drilling.
  2. First polar body morphology and blastocyst formation rate in ICSI patients
  3. Should ICSI be the treatment of choice for all cases of in-vitro conception?: No, not in light of the scientific data.
  4. Polycystic ovarian syndrome

1. PCOS and ovarian drilling

Currently, there is an uncertainty about the impact of laparoscopic ovarian drilling (LOD) on the natural history of polycystic ovarian syndrome (PCOS). This longitudinal follow-up study was undertaken to investigate the long-term effects of LOD. The study included 116 anovulatory PCOS women who underwent LOD between 1991 and 1999 (study group) and 34 anovulatory PCOS women diagnosed during the same period but who had not undergone LOD (comparison group). The hospital records were reviewed and questionnaires were sent to all the women. In addition, most women attended a follow-up interview. Clinical data recorded at different intervals of follow-up (short-term, <1 year; medium-term, 1-3 years; and long-term, 4-9 years) included: the menstrual pattern, symptoms relating to hyperandrogenaemia and reproductive history. LOD produces long-term improvement in menstrual regularity and reproductive performance in about one-third of cases. A modest and sustained improvement in acne and hirsutism can be expected in approximately 40 and approximately 25% of patients respectively.


Amer SA, Gopalan V, Li TC, Ledger WL, Cooke ID Long term follow-up of patients with polycystic ovarian syndrome after laparoscopic ovarian drilling: clinical outcome. Hum Reprod. 2002 Aug;17(8):2035-42.

2. First polar body morphology and blastocyst formation rate in ICSI patients

It may be beneficial to identify, at a very early stage of development, concepti that will result in viable blastocysts by using a non-invasive technique. In this study homogeneous groups in terms of first polar body (PB) morphology were analysed with regard to fertilization, embryo quality and blastocyst formation. The strategy was to transfer a maximum of two blastocysts with an adequate inner cell mass deriving from oocytes with identical first PBs in order to obtain information about the actual implantation potential. A significant relationship between first PB morphology and embryo quality was found. Fragmentation after 2 days was increased in embryos derived from oocytes with fragmented first PBs (P < 0.05) in comparison with those derived from oocytes with intact PBs. No similar correlation could be demonstrated for fertilization rate. Embryos in the intact first PB group showed an increased rate of blastocyst formation as compared with the fragmented first PB group (P < 0.05). In addition, a significant difference in implantation rate (48.6 versus 22.0%; P < 0.025) and ongoing pregnancy rate (68.4 versus 34.8%; P < 0.05) was observed for the intact versus fragmented groups respectively. In conclusion, the current study provides further evidence that preselection at a very early stage may be helpful in identifying a subgroup of preimplantation embryos with a good prognosis to form blastocysts and, consequently, to implant.


Ebner T, Moser M, Sommergruber M, Yaman C, Pfleger U, Tews G. First polar body morphology and blastocyst formation rate in ICSI patients. Hum Reprod. 2002 Sep;17(9):2415-8.

3. Should ICSI be the treatment of choice for all cases of in-vitro conception?: No, not in light of the scientific data.

There is an ongoing debate among reproductive endocrinologists and embryologists about the indications for ICSI in the management of the infertile couple. Analysis of published results indicates that there are no data to suggest that ICSI should be performed in all cases of in-vitro conception. If the results of the basic semen analysis and sperm function tests demonstrate an impairment of sperm fertilizing capacity, couples should be directed to ICSI. In cases of previous fertilization failure, ICSI usually results in an improved outcome. This suggests the presence of 'occult' male or female gamete defects that can be bypassed by ICSI. It is stressed that efforts should be geared toward the identification of the aetiology and pathophysiology of sperm and oocyte lesions/dysfunctions responsible for fertilization impairment and their potential contributions to defective embryogenesis. A better definition of the indications for ICSI is needed, together with the development of directed, simpler, less expensive and safer alternatives.


Oehninger S, Gosden RG. Should ICSI be the treatment of choice for all cases of in-vitro conception?: No, not in light of the scientific data. Hum Reprod. 2002 Sep;17(9):2237 42.

3. Polycystic ovarian syndrome

Polycystic ovary syndrome (PCOS) is a true syndrome, being a heterogeneous collection of signs and symptoms that gathered together form a spectrum of a disorder with a mild presentation in some, whilst in others there is a severe disturbance of reproductive, endocrine and metabolic function. There has been much debate about phenotype and, more recently, genotype. There has also been scepticism in some quarters, with a feeling that we may be looking at one end of a spectrum that is in reality 'normal', or perhaps a consequence of the modern disease of obesity. Whilst the polycystic ovary is at the centre of the syndrome, it is external effects such as hyperinsulinism, that influence its expression. There is no consensus on the definition of PCOS and so studies that compare epidemiology and treatments often have very different starting points, and so cannot be compared. In this debate we wish to re-explore our current thinking on PCOS, with a particular emphasis on the British and European perspective and invite others to contribute to the discussion which could form the basis for an international consensus.

The existing literature provides a strong basis for arguing that PCOS clusters in families. However, the mode of inheritance of the disorder is still uncertain, although the majority of studies are consistent with an autosomal dominant pattern, modified perhaps by environmental factors. In addition, studies on PCOS cells (theca, muscle, and adipocytes) in culture have documented a persistent biochemical and molecular phenotype that distinguishes them from normal cells. Although several loci have been proposed as PCOS genes including CYP11A, the insulin gene, and a region near the insulin receptor, the evidence supporting linkage is not overwhelming. The strongest case can be made for the region near the insulin receptor gene, as it has been identified in two separate studies. However, the responsible gene at chromosome 19p13.3 remains to be identified. Association studies have provided a number of potential loci with genetic variants that may create or add to a PCOS phenotype, including Calpain 10, IRS-1 and -2, and SHBG. Collectively, these findings are consistent with the concept that a gene or several genes are linked to PCOS susceptibility. Because the mutations/genotypes associated with PCOS are rare, and their full impact on the phenotype incompletely understood, routine screening of women with PCOS or stigmata of PCOS for these genetic variants is not indicated at this time. Currently the treatment implications for individually identified genetic variants is uncertain and must be addressed on a case by case basis.

Insulin resistance is a prominent feature of polycystic ovarian syndrome (PCOS), and women with the disorder are at increased risk for the development of other diseases that have been linked to insulin resistance-namely, type 2 diabetes and cardiovascular disease. The recognition of insulin resistance as a principal factor in the pathogenesis of polycystic ovarian syndrome (PCOS) has led to the use of insulin-lowering agents, also called 'insulin-sensitizing drugs', for its treatment. The most extensively studied insulin-lowering agent in the treatment of PCOS is metformin: an oral antihyperglycaemic agent used initially in the treatment of type 2 diabetes mellitus. Metformin is effective in the treatment of PCOS-related anovulation and infertility. Moreover, preliminary evidence indicates that metformin may also be effective in decreasing the risk of early spontaneous miscarriage in women with PCOS. Metformin also appears to induce cardioprotective effects on serum lipids as well as plasminogen activator inhibitor (PAI)-1 and may decrease the risk of development of type 2 diabetes. The highly promising therapeutic profile of metformin is related to the role of this agent in controlling an important aetiologic factor in the pathogenesis of PCOS: hyperinsulinaemia. Limited evidence exists to suggest that oral contraceptive pills-the currently standard therapy for PCOS-may actually decrease insulin sensitivity and induce impaired glucose tolerance in women with PCOS. Hence, PCOS should be regarded as a general health issue and the use of insulin-sensitizing drugs such as metformin should be considered for the prevention of type 2 diabetes.


Balen A, Michelmore K. What is polycystic ovary syndrome?: Are national views important? Hum Reprod. 2002 Sep;17(9):2219-27.

Legro R, Strauss J. Molecular progress in infertility: polycystic ovary syndrome. Fertil Steril. 2002 Sep;78(3):569.

Nestler JE. Should patients with polycystic ovarian syndrome be treated with metformin?: An enthusiastic endorsement. Hum Reprod 2002 Aug;17(8):1950-3.

Seli E, Duleba AJ. Should patients with polycystic ovarian syndrome be treated with metformin? Hum Reprod. 2002 Sep;17(9):2230-6.

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Gerhard Leyendecker