Lilli P. Thorsell

Intracytoplasmic sperm injection facilitates fertilization even in the most severe forms of male infertility: pregnancy outcome correlates with maternal age and number of eggs available

OBJECTIVE To evaluate, in a prospective study, the fertilization and pregnancy rates after intracytoplasmic sperm injection (ICSI) in infertile couples with severe male infertility. DESIGN Intracytoplasmic sperm injection was performed in 229 consecutive IVF cycles on 190 couples with rigorously defined severe male infertility or proven failure of fertilization in prior IVF cycles. Neither male nor female partners were chosen from a waiting list or on any other selective basis, including age, prior or anticipated ovarian response, or oocyte number or quality. There were no upper age limits, in no instance was donor sperm used for ICSI, and cycle cancellation rate was minimal. SETTING Private genetics and fertility center in Fairfax, Virginia. MAIN OUTCOME MEASURES Fertilization, transfer, and pregnancy rates were measured in ICSI-treated couples, and comparisons were made regarding both female age and strictly defined semen categories. RESULTS Two hundred six cycles (90%) resulted in ETs, with initiation of 52 pregnancies (25% per transfer, 23% per cycle). Thirty-eight of 52 (18% per transfer) were clinical pregnancies with established gestational sacs or were ongoing or delivered. Pregnancies were achieved even in older women but were more readily established in younger women producing larger numbers of metaphase II oocytes. The severity of semen abnormalities had some small effect on fertilization rate, but only actual necrospermia was associated with markedly decreased frequency of embryo formation. Pregnancy per transfer was similar across groups. In some cases, pregnancy was initiated with fewer than 100 viable sperm in the ejaculate. CONCLUSIONS Intracytoplasmic sperm injection is a very powerful new treatment for severe male infertility. Paradoxically, egg number and probably egg quality are now the main determinants of success in treating male infertility.

Validation of an Embryotoxicity Assay

PROBLEM: Culture of mouse blastocysts has served as a tool for identifying various embryotoxic factors in human serum. While inactivated, sera from recurrently aborting women inhibit mouse blastocyst development in vitro. Variation in results from individual serum samples has limited the usefulness of this assay in establishing a new classification of idiopathic recurrent spontaneous abortion (RSA).

Comparisons of pregnancy loss patterns after intracytoplasmic sperm injection and other assisted reproductive technologies

OBJECTIVE To compare outcome of pregnancies after intracytoplasmic sperm injection (ICSI) with those of other assisted reproductive technologies. DESIGN Pregnancy outcomes after ICSI were followed prospectively and compared with pregnancy outcomes after IVF with fresh and frozen ETs and donor oocyte cycles. SETTING A private tertiary referral center for genetics and infertility in Fairfax, Virginia. PATIENTS One hundred thirty-six couples achieving pregnancy after undergoing ICSI, 71 after IVF, 35 donor oocyte recipients, and 19 after transfer of frozen-thawed embryos. INTERVENTIONS In vitro fertilization and/or ET for all couples. Dilatation and curettage to obtain products of conception for chromosome analysis in 28 women experiencing spontaneous abortion. MAIN OUTCOME MEASURES Pregnancy outcomes were classified as preclinical loss, clinical loss, and ongoing pregnancy. RESULTS The mean frequency of preclinical pregnancy loss was 26% after ICSI, 28% after IVF, 3% after ET using donor oocytes, and 11% after frozen ET. The rate of clinical loss after ICSI (21%) was compared with IVF (18%), donor oocyte cycles (11%), and frozen ETs (21%). CONCLUSIONS Intracytoplasmic sperm injection is not associated with an increase in pregnancy losses, clinical or preclinical, compared with conventional IVF.

The number of embryos available for transfer predicts successful pregnancy outcome in women over 39 years with normal ovarian hormonal reserve testing.

AbstractPurpose: The purpose was to determine whether the number of embryos available for transfer following IVF in women over age 39 predicted a successful pregnancy outcome. Methods: Retrospective analysis of 455 consecutive IVF cycles in women ≥ years of age. Results: Few cycles were canceled (29/455, 6.4%) or produced no embryos (5/455, 1.1%). Women 40–43 years of age with normal ovarian reserve had a significantly greater delivery rate when ≥4 embryos were available for transfer than when <4 embryos were available (17.8% versus 2.4%, P = 0.002). Subsequent IVF cycles, from women with normal FSH whose first cycle produced <4 embryos, produced delivery rates of 13.0% when ≥4 embryos were available. Women with abnormal ovarian reserve or age ≥44 years had very low delivery rates (1.2% and 1.4% respectively). Conclusions: The number of embryos available for transfer significantly predicts delivery from IVF–ET among reproductively older women. Many women age 40–43 with normal ovarian reserve can achieve pregnancy through IVF.

Donor Oocyte Cytoplasmic Transfer Did Not Enhance Implantation of Embryos of Women with Poor Ovarian Reserve

AbstractPurpose: To determine whether donor oocyte cytoplasm transferred into the oocytes of women ≥40 years or with diminished ovarian reserve would enhance embryo quality, implantation, or pregnancy rates. Methods: Study subjects included women ≥40 years (15) or with abnormal FSH levels (3). Healthy volunteers (18) produced oocytes for cryopreservation. Donor oocytes were thawed and cytoplasm from surviving oocytes was injected with a single sperm into the cytoplasm of recipient oocytes. Outcome measures included embryo quality scores, implantation, and pregnancy rates. Results: Eighteen donors produced 213 oocytes for cryopreservation and 39/171 (22.8%) survived thawing. Eighteen recipients initiated 25 IVF cycles with embryo transfer in 20 cycles after cytoplasmic transfer (CT). Four cycles resulted in three biochemical losses and one aneuploid clinical loss. Embryo quality did not improve with CT compared to pre-CT IVF cycles in six recipients. Conclusions: CT with cryopreserved donor oocyte cytoplasm did not enhance success in women with advanced reproductive age or low ovarian reserve.