Mausumi Das

Recurrent implantation failure: gamete and embryo factors

Chromosomal abnormalities, sperm DNA damage, zona hardening, inadequate culture conditions, and suboptimal embryo development all play a significant role in the etiology of recurrent implantation failure. Evidence suggests that preimplantation genetic screening does not increase implantation or live birth rates. Comparative genomic hybridization array and analysis of single nucleotide polymorphisms could enable a more comprehensive screening of chromosomes. Assisted hatching may help to overcome zona hardening in selected cases. Optimal culture conditions and blastocyst transfer could contribute toward improving implantation and pregnancy rates. Novel embryo assessment and selection procedures, such as time-lapse imaging and metabolomics, may help in better evaluation of embryo quality and viability and help in selecting embryos with the highest implantation potential. The safety and efficacy of emerging treatment modalities should be evaluated in prospective randomized clinical trials before being applied in routine clinical practice.

Ovarian reserve, response to gonadotropins, and oocyte maturity in women with malignancy

OBJECTIVE To study the ovarian reserve, ovarian response to gonadotropins, and oocyte maturity in women with cancer undergoing in vitro fertilization (IVF) before chemotherapy or radiotherapy. DESIGN Case-control study. SETTING University teaching hospital. PATIENT(S) We evaluated all women with malignancy who underwent fertility preservation from the year 2003 to 2010. We compared 41 women with cancer undergoing IVF treatment with a control group of 48 age-matched women undergoing IVF for male factor infertility with the same protocol. INTERVENTION(S) In vitro fertilization. MAIN OUTCOME MEASURES(S) Ovarian reserve, ovarian response to gonadotropins, number of oocytes retrieved, and oocyte maturity. RESULT(S) There were no significant differences in age, antral follicle count, serum FSH, total dose of gonadotropins required for stimulation, duration of stimulation, or peak E(2) levels on the day of hCG administration between women with cancer and the control group. No significant differences were observed in the number of retrieved oocytes between the malignancy and control groups. The percentages of mature oocytes in patients with hematologic malignancy (83.3%), gynecologic and intestinal malignancy (94%), and brain cancer (86%) and in the control group (82.1%) were similar, as were the fertilization rates. CONCLUSION(S) In young women with malignancy, ovarian reserve, response to gonadotropins, oocytes retrieved, and oocyte maturity remain unaltered by the neoplastic process. This is in contrast to the impairment of spermatogenesis before therapy in men with cancer.

Ovarian reserve and oocyte maturity in women with malignancy undergoing in vitro maturation treatment.

OBJECTIVE To evaluate ovarian reserve and oocyte maturity in women with malignancy. DESIGN A case-control study. SETTING University teaching hospital. PATIENT(S) We evaluated all women with malignancy who underwent in vitro maturation treatment for fertility preservation from the year 2003 to 2009. The results were compared with those of an age-matched infertile control group. INTERVENTION(S) In vitro maturation treatment. MAIN OUTCOME MEASURE(S) Ovarian reserve and oocyte maturity. RESULT(S) Women with malignancy of the breast (n = 87), hematologic malignancy (n = 16), gynecologic or abdominal malignancy (n = 9), and other malignancies (n = 16) were compared with infertile control women (n = 79). The age was similar in all groups except in women with hematologic malignancy where they were younger than the control group (24.9 ± 1.1 years vs. 30.8 ± 0.4 years, confidence interval 4.0-9.5). Baseline FSH in this group was also lower than in the control group. Women with breast cancer had a lower number of retrieved oocytes than the control group (95% confidence interval 0-5). There were no significant differences in antral follicle count, percentage of mature oocytes on collection day, and percentage of metaphase II oocytes matured in vitro among all groups of women. CONCLUSION(S) Women with breast cancer have fewer numbers of retrieved oocytes than infertile controls. Ovarian reserve and oocyte maturity in other types of malignancy are similar to those in the control group.

Ovarian stimulation and intrauterine insemination in women aged 40 years or more

Fertility decreases with advancing age. This study retrospectively reviewed the results of ovarian stimulation and intrauterine insemination (IUI) in women 40 years old with diminished ovarian reserve or unexplained infertility who underwent treatment with ovarian stimulation/IUI with clomiphene citrate or gonadotrophin and compared them with the results of IVF and in-vitro maturation (IVM) treatments. The main outcome measures were pregnancy and live-birth rates. The profiles of the patients in ovarian stimulation, IVM and IVF groups were comparable. There were no clinical pregnancies in the clomiphene citrate and IVM groups. The clinical-pregnancy rates in the gonadotrophin and IVF groups were 2.6% and 16.9% and the live-birth rates were 2.6% and 13.7%, respectively. Compared with ovarian stimulation, IVF is most effective for women aged 40 years or more. Attempting success with ovarian stimulation or IVM will delay conception unnecessarily.

In-vitro maturation versus IVF with GnRH antagonist for women with polycystic ovary syndrome: treatment outcome and rates of ovarian hyperstimulation syndrome

In-vitro maturation (IVM) treatment has gained popularity for decreasing the incidence of ovarian hyperstimulation syndrome (OHSS) by eliminating or minimizing the use of gonadotrophins in women with polycystic ovary syndrome (PCOS). Studies have shown that IVF with GnRH-antagonist protocol is associated with a lower incidence of OHSS. Data comparing the relative success of these two treatments is, however, lacking. Treatment outcome and rates of OHSS were compared in patients with PCOS who underwent assisted conception with either IVM or IVF with GnRH-antagonist protocol between 2006 and 2011. The number of oocytes retrieved was higher in the IVM group, whereas the number of mature oocytes, fertilization rate and number of embryos cleaved were comparable. The implantation rate was higher in the IVF group. The clinical pregnancy rates per embryo transfer were not statistically different (IVF: 45.8% versus IVM: 32.4%). The live-birth rate was higher in the IVF group (IVF: 40.7% versus IVM: 23.5%; P = 0.04). Five women developed moderate or severe OHSS in the IVF group, whereas none did in the IVM group. Both IVM and IVF with GnRH-antagonist protocol seem to be effective treatment regimens in women with PCOS, although IVM is associated with a lower risk of OHSS.

Long-acting Gonadotropins and Route of Administration

Advances in recombinant DNA technologies have led to the development of longer-acting preparations with prolonged follicle-stimulating bioactivity. Corifollitropin alfa is a synthetic recombinant follicle-stimulating hormone (r-FSH) molecule containing a hybrid beta subunit, which provides prolonged follicle-stimulating activity while maintaining its pharmacodynamic activity. In controlled ovarian stimulation, long-acting gonadotropins have the ability to initiate and sustain multifollicular growth for 7 days. Current evidence suggests that the use of a medium dose of long-acting FSH is a safe treatment option and equally effective compared to daily FSH. This simplified treatment approach may provide a more patient-friendly approach to controlled ovarian stimulation. Further research is needed to determine whether long-acting FSH is safe and efficacious in patients at risk of ovarian hyperstimulation or poor responders. Studies are also needed to assess patient satisfaction and overall patient experience with the long-acting FSH preparations. Novel drug delivery systems developments will ultimately lead to greater ease of administration, more simplified and convenient dosing regimens and superior safety and efficacy, ultimately leading to greater patient satisfaction and improved patient experience.

UAE is not Recommended for Women Wishing to Conceive

Although considered a fertility saving option in women of reproductive age, current evidence suggests that uterine artery embolization can have an adverse effect on ovarian function as well as on future pregnancies. Uterine artery embolization is associated with a risk of premature ovarian failure, as well as occasional injury to the endometrium resulting in endometrial atrophy and adhesion formation. All of these including a subtle reduction in the ovarian reserve jeopardise fertility. Pregnancies following uterine artery embolization can be complicated by an increased rate of miscarriage, preterm delivery, intra-uterine growth restriction, malpresentation, abnormal placentation and post-partum hemorrhage. In view of the possibility of impaired ovarian function as well as increased pregnancy complications, women with fibroids who wish to conceive should not be treated with uterine artery embolization. Myomectomy should be recommended as the treatment of choice over uterine artery embolization in women desiring future fertility. The effect of uterine artery embolization for post-partum hemorrhage on future fertility is currently uncertain.