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Natural Cycle In-Vitro Fertilization in Couples with Unexplained Infertility: Impact of Various Factors on Outcome

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Natural Cycle In-Vitro Fertilization in Couples with Unexplained Infertility: Impact of Various Factors on Outcome Human Reproduction vol.12 no.ll pp.2402-2407, 1997 Natural cycle in-vitro fertilization in couples with unexplained infertility: impact of various factors on outcome F.Zayed1'3, E.A.Lenton1'2 and I.D.Cooke2 The first live birth following IVF occurred in 1978 and was a consequence of IVF performed in the natural cycle 'Sheffield Fertility Centre, 26 Glen Road, Sheffield S7 IRA and 2University Department of Obstetrics and Gynaecology, of a woman with tubal infertility (Edwards et al, 1980). Downloaded from https://academic.oup.com/humrep/article/12/11/2402/664697 by guest on 30 September 2021 Jessop Hospital for Women, Sheffield S3 7RE, UK This success encouraged a number of groups to attempt NIVF, but they experienced difficulties (Johnston et al, 3To whom correspondence should be addressed at: Department of Obstetrics and Gynaecology, Jordan University of Science and 1981; Jones et al, 1982). NIVF was quickly abandoned in Technology, P.O. Box 962106, Amman-11196, Jordan favour of stimulated IVF (SIVF), which yielded higher pregnancy rates as a consequence of transferring several This study evaluated outcome in 117 couples with un- embryos (Wood et al, 1985; Testart et al, 1986). However, explained infertility who underwent 162 attempts at recently interest in NIVF has revived because of concerns natural cycle in-vitro fertilization (NIVF) between 1991 surrounding ovarian stimulation. These include ovarian and 1993. An egg was obtained in 138 cycles and a hyperstimulation syndrome, multiple pregnancies (Rizk single embryo was transferred in 89 cycles. There were 16 et al, 1991; Tan et al, 1992), a possible decrease in implantations (four biochemical pregnancies, three clinical endometrial receptivity (Paulson et al, 1990), the emotional abortions and nine live births). The implantation rate per 'roller coaster' of IVF-embryo transfer (Claman et al, embryo was 16/89 (18.0%), which translated into a live 1993), a suggested increased risk of developing ovarian birth rate per egg collection of 9/138 (6.5%). The impact cancer (Whittemore et al, 1991; Spirtas et al, 1993), factors that were assessed included oocyte quality, sperm legal and ethical dilemmas associated with storage and quality, embryo quality and woman's age. The outcome disposal of surplus embryos and the rising cost of stimulation measures used were fertilization/inseminated egg and as a consequence of the introduction of recombinant implantation/replaced embryo. All embryo transfers were drugs. of single embryos. We conclude that, in couples with Ranoux et al (1988) reported a NIVF pregnancy rate of unexplained infertility, outcome following NIVF is affected 20% per embryo transfer that later increased to 32% in an by both egg and sperm quality and by the age of the expanded series (Foulot et al, 1989). Svalander et al. (1991), woman. Embryo quality was independent of the above Lenton et al. (1992) and Paulson et al. (1992) all reported factors but was also critical for successful implantation. reasonable pregnancy rates following NIVF which Claman Key words: implantation/in-vitro fertilization/natural cycle/ et al (1993) and DeLauretis et al (1994) were unable to unexplained infertility confirm. Fertilization rates in NIVF studies have been reported to vary from 50 to 90%, depending on whether the spontaneous luteinizing hormone (LH) surge was used to time egg recovery (Lenton et al, 1992; Taymor et al, 1992; DeLauretis et al, Introduction 1994) or human chorionic gonadotrophin (HCG) was given As the name implies, the mechanism(s) resulting in infertility (Muasher et al, 1980; Foulot et al, 1989; Svalander et al, in those couples designated as having unexplained infertility 1991; Paulson, 1993; Claman et al, 1993; DeLauretis et al, are unknown. It can be speculated that there may be occult 1994; Scarduelli et al, 1994). Few studies have described problems in either the oocyte or the spermatozoon, leading to outcomes in patients selected by type of infertility (Fahy et al., fertilization failure or dysfunctional embryos, or at the level 1995) or have assessed cost-effectiveness and other factors of the endometrium, resulting in implantation failure. Conven- (Daya et al, 1995). In the UK, NIVF is now only rarely tional infertility investigations consisting of a semen analysis performed as a direct consequence of the negative impact of and tests to assess ovulatory status and tubal patency are the inevitably lower pregnancy outcomes on overall clinic unable to detect subtle functional disorders. performance reflected in comparative data published annually Natural cycle in-vitro fertilization (NIVF) has been used to by the Human Fertilisation and Embryology Authority (HFEA, treat unexplained infertility, but the pregnancy rates are rela- 1995 and 1996 Patient Guides). tively low (Lenton et al, 1992). Despite this, NIVF is a good The following retrospective analysis of NIVF undertaken in model for assessing fertilization and embryo development couples with unexplained infertility aimed to study the impact under spontaneous or natural cycle conditions. Information of various gamete-associated parameters on implantation rates gained from the analysis of such studies may yield insights into in the hope that this would give some insight into the factors the importance of the contribution of the egg, spermatozoon and that may be important for success. embryo to successful pregnancy outcome. 2402 © European Society for Human Reproduction and Embryology Natural cycle IVF in unexplained infertility Table I. The impact of female age on the proportion of oocytes suitable for insemination, the percentage of oocytes which fertilized and the implantation rate (human chorionic gonadotrophin >10 U/l) following single embryo transfer in the natural cycle relative to the implantation rate per egg collection cycle Female All cycles Oocytes Fertilization Implantation Implantation age with suitable for per inseminated per replaced per cycle with (years) oocytes (%) insemination (%) oocyte (%) embryo (%) oocytes (%) 24-29 22 91 85 17.6 13.6 30-35 73 96 73 19.1 12.3 36-40 35 91 69 19.0 11.4 41-44 8 75a 67 0 0 aThere were significantly fewer (P < 0.05) suitable oocytes retrieved from older women relative to those =£40 years. Downloaded from https://academic.oup.com/humrep/article/12/11/2402/664697 by guest on 30 September 2021 Methods and materials of NIVF and the quality of both sperm and eggs were analysed for their impact on fertilization, as well as for embryo development and Subjects implantation. The differences were considered significant at a level The Sheffield Fertility Centre has extensive experience of NIVF. This of P < 0.05. study is a retrospective analysis of all cases of unexplained infertility treated by NIVF between 1991 and 1993. Unexplained infertility was defined according to the following criteria: duration of infertility ^2 Results years, regular menstrual cycles (25-34 days), patent tubes diagnosed The analysis included 117 couples studied during 162 NIVF by laparoscopy or hysterosalpingography and a normal semen analysis using local criteria of concentration >20X 106 spermatozoa/ cycles. Seven cycles were cancelled due to poor follicular ml, motility >30% (grades I+II), normal morphology >25% and growth or dysfunctional ovulation, and in 10 cycles the women antisperm antibodies <25%. The age of the female partners ranged ovulated spontaneously prior to egg collection. Eggs were from 24 to 44 years and that of the male partners from 22 and 49 obtained in 138 of the 145 cycles (93.2%) undergoing follicular years; duration of infertility was from 2 to 19 years. aspiration; 128 of the eggs obtained were normal (92.8%) and were inseminated and 94 (73.4%) fertilized with two pronuclei. Natural cycle IVF Of these, 89 single embryos were replaced, resulting in 16 All the IVF cycles were completely natural, clomiphene citrate was implantations (four biochemical pregnancies, three clinical not used and all egg collections were performed following detection of the spontaneous LH surge. Blood was taken for base line plasma abortions and nine live births). The overall implantation rate LH and follicle stimulating hormone (FSH) concentrations on day 2 per cycle was 16/162 (9.9%), while the implantation rate per and then twice daily from day 9 of the cycle for measurement of cycle with an egg was 16/138 (11.6%) and the implantation oestradiol and to detect the onset of the LH surge. The precise time rate per single embryo replaced was 16/89 (18.0%). The live of onset of the LH surge was calculated by interpolation from tables birth rate per cycle with egg collection was 9/138 (6.5%). derived from LH profiles obtained during earlier studies of NIVF (see Figs. 1, 2 and 3 in Lenton et al., 1992). Egg collection was Female age ideally timed to be ~34—36 h from the onset of the spontaneous LH To study the impact of female age, patients were divided into surge and was performed using transvaginal ultrasound (Ramsewak et al., 1990). Measurements of LH and oestradiol were performed four groups: 24-29, 30-35, 36-40 and 41^4 years of age using enzyme immunoassay (Serozyme; Serono Diagnostics Limited, (Table I). The proportion of oocytes suitable for insemination Surrey, UK). All semen samples for IVF were prepared by Percoll (i.e. normal oocytes) was constant at 91-96%, except in women density centrifugation. Oocytes were conventionally fertilized in vitro aged >40 years, when it declined to 75% (P < 0.05). and single embryos were transferred 2-3 days after follicle aspiration. Fertilization rates also declined slowly but steadily with Luteal support was with dydrogesterone (30 mg daily, Duphaston; increasing age, from 85% in the youngest group to 67% in Solvay Healthcare Ltd, Southampton, UK). Implantations were identi- women >40 years. Surprisingly, implantation rates per embryo fied by serially rising HCG concentrations and later confirmed as a remained constant up to the age of 40 years, but no implanta- clinical pregnancy when an intrauterine gestation sac was seen on tions were achieved in the eight women aged 2=41 years in ultrasound.
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